array:24 [
  "pii" => "S0873215913000536"
  "issn" => "08732159"
  "doi" => "10.1016/j.rppneu.2013.03.006"
  "estado" => "S300"
  "fechaPublicacion" => "2013-11-01"
  "aid" => "155"
  "copyright" => "Sociedade Portuguesa de Pneumologia"
  "copyrightAnyo" => "2013"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "ssu"
  "cita" => "Rev Port Pneumol. 2013;19:266-75"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 24252
    "formatos" => array:3 [
      "EPUB" => 302
      "HTML" => 21216
      "PDF" => 2734
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S0873215913000950"
    "issn" => "08732159"
    "doi" => "10.1016/j.rppneu.2013.06.006"
    "estado" => "S300"
    "fechaPublicacion" => "2013-11-01"
    "aid" => "172"
    "copyright" => "Sociedade Portuguesa de Pneumologia"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "sco"
    "cita" => "Rev Port Pneumol. 2013;19:276-80"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 7001
      "formatos" => array:3 [
        "EPUB" => 239
        "HTML" => 5552
        "PDF" => 1210
      ]
    ]
    "pt" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Publica&#231;&#227;o breve</span>"
      "titulo" => "Aplica&#231;&#227;o t&#243;pica de mitomicina-<span class="elsevierStyleSmallCaps">C</span> como adjuvante no tratamento broncosc&#243;pico da estenose traqueal p&#243;s-entuba&#231;&#227;o"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => array:2 [
        0 => "pt"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "276"
          "paginaFinal" => "280"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Topical application of mitomycin-C as an adjuvant treatment to bronchoscopic procedures in post-intubation tracheal stenosis"
        ]
      ]
      "contieneResumen" => array:2 [
        "pt" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1017
              "Ancho" => 1660
              "Tamanyo" => 144536
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Resultados do tratamento com BR&#47;MMC apresentados por percentagem de estenose do l&#250;men traqueal&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "F&#46; Viveiros, J&#46; Gomes, A&#46; Oliveira, S&#46; Neves, J&#46; Almeida, J&#46; Moura e S&#225;"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "Viveiros"
            ]
            1 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Gomes"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Oliveira"
            ]
            3 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Neves"
            ]
            4 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Almeida"
            ]
            5 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Moura e S&#225;"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S2173511513000705"
        "doi" => "10.1016/j.rppnen.2013.10.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511513000705?idApp=UINPBA00004E"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215913000950?idApp=UINPBA00004E"
    "url" => "/08732159/0000001900000006/v2_201509041406/S0873215913000950/v2_201509041406/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0873215913000846"
    "issn" => "08732159"
    "doi" => "10.1016/j.rppneu.2013.03.007"
    "estado" => "S300"
    "fechaPublicacion" => "2013-11-01"
    "aid" => "169"
    "copyright" => "Sociedade Portuguesa de Pneumologia"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Rev Port Pneumol. 2013;19:260-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 6419
      "formatos" => array:3 [
        "EPUB" => 264
        "HTML" => 4929
        "PDF" => 1226
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Is <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT prognostic factor for survival in patients with small cell lung cancer&#63; Single center experience"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "260"
          "paginaFinal" => "265"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "&#201; o <span class="elsevierStyleSup">18</span>F -FDG-PET&#47;CT um fator de progn&#243;stico para a sobreviv&#234;ncia em pacientes com cancro pulmonar de pequenas c&#233;lulas&#63; Experi&#234;ncia num &#250;nico centro"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1453
              "Ancho" => 1394
              "Tamanyo" => 90137
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Survival of patients according to performance status&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "A&#46; Inal, M&#46; Kucukoner, M&#46;A&#46; Kaplan, Z&#46; Urakc&#305;, N&#46; Nas, M&#46; Guven, Z&#46; Dostbil, S&#46; Alt&#305;ndag, A&#46; Is&#305;kdogan"
          "autores" => array:9 [
            0 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Inal"
            ]
            1 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Kucukoner"
            ]
            2 => array:2 [
              "nombre" => "M&#46;A&#46;"
              "apellidos" => "Kaplan"
            ]
            3 => array:2 [
              "nombre" => "Z&#46;"
              "apellidos" => "Urakc&#305;"
            ]
            4 => array:2 [
              "nombre" => "N&#46;"
              "apellidos" => "Nas"
            ]
            5 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Guven"
            ]
            6 => array:2 [
              "nombre" => "Z&#46;"
              "apellidos" => "Dostbil"
            ]
            7 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Alt&#305;ndag"
            ]
            8 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Is&#305;kdogan"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215913000846?idApp=UINPBA00004E"
    "url" => "/08732159/0000001900000006/v2_201509041406/S0873215913000846/v2_201509041406/en/main.assets"
  ]
  "en" => array:18 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "New advances in the therapy of non-cystic fibrosis bronchiectasis"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "266"
        "paginaFinal" => "275"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "A&#46; Amorim, F&#46; Gamboa, P&#46; Azevedo"
        "autores" => array:3 [
          0 => array:4 [
            "nombre" => "A&#46;"
            "apellidos" => "Amorim"
            "email" => array:1 [
              0 => "adelinamorim&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "Gamboa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "P&#46;"
            "apellidos" => "Azevedo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Pneumology Department&#44; Centro Hospitalar S&#227;o Jo&#227;o&#44; EPE&#44; Faculty of Medicine&#44; University of Porto&#44; Porto&#44; Portugal"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Pneumology Department&#44; Centro Hospitalar e Universit&#225;rio de Coimbra-Hospitais da Universidade de Coimbra&#44; EPE&#44; Coimbra&#44; Portugal"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Pneumology Department&#44; Centro Hospitalar Santa Maria&#44; Faculty of Medicine&#44; University of Lisbon&#44; Lisbon&#44; Portugal"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "pt" => array:1 [
        "titulo" => "Novos avan&#231;os no tratamento da Bronquiectasia n&#227;o-fibrose c&#237;stica"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bronchiectasis &#40;BE&#41; is an abnormal and irreversible dilation of the bronchi&#44; which has numerous causes&#46; Its frequency depends on the patient&#39;s age and sex&#44; social and economic conditions and the degree of applied investigation&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">There was little interest in the investigation of non-cystic fibrosis BE&#44; this includes therapeutic approaches&#44; in the last few decades&#44; probably due to supposedly low prevalence and the assumption that treatment is the same for all patients and that little can be done to change the symptoms and evolution&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The publication of diagnosis and treatment reviews in the last few years<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> demonstrates a growing interest in this pathology&#46; The level of evidence for most recommendations however is low&#44; because of the absence of large double-blind&#44; placebo-controlled trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The existence of strong evidence supporting the use of some drugs in patients with cystic fibrosis &#40;CF&#41; does not mean that they will be good for patients with BE of another etiology&#46; So&#44; it is not correct to extrapolate the CF trial results to the non-CF patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In CF&#44; the forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s &#40;FEV1&#41; is one of the most important trial end-points&#46; In non-CF BE it has been difficult to establish appropriate end-points to evaluate the effect of new therapeutic interventions&#46; To date it seems that improvement in quality of life is one of the most important outcome measures&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">BE is characterized by a vicious cycle of infection&#44; inflammation and further sputum production&#46; In this review we decided to focus on three important pharmacological groups that aim to interfere with each part of the cycle and in which there have been relevant advances&#46; Nevertheless&#44; BE treatment should be embraced and specific therapies for the underlying cause as well as interventions like physiotherapy&#44; pulmonary rehabilitation&#44; nutritional support and&#44; in selected patients&#44; surgical intervention need to be kept in mind&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Mucoactive therapy</span><p id="par0035" class="elsevierStylePara elsevierViewall">Regardless of the cause&#44; BE is mainly characterized by bronchial infection and persistent inflammation which could be the cause and consequence of impaired airway mucous clearance&#46; The mucus progressively becomes viscous due to the presence of inflammatory cells&#44; microorganisms and large polymers and turns into sputum&#44; overwhelming the ciliary clearance capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The mucus clearance requires a balance between periciliary liquid volume&#44; mucus composition and volume and normal ciliary beat frequency&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> One of these steps could be more particularly affected depending on the cause of BE&#59; the therapeutic intervention should ideally be focused on the main mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Unfortunately in many cases this is not clear and there is probably a mix of mechanisms involved so the development of combined therapies would be more appropriate&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The pathogenesis process mostly accepted in CF indicates a relative dehydration and a reduction in airway surface liquid volume&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Therefore airway hydration is an important goal in the overall therapeutic management of this disease&#46; However&#44; it is generally accepted that even in the absence of dehydration the increase in water improves mucus clearance by decreasing surface interactions&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In this context the most recent advances in the treatment of mucociliary dysfunction are targeted at increasing hydration on airway surface by inhaled hyperosmolar agents&#44; like mannitol and hypertonic saline &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Both the agents increase the osmolarity of the airway surface fluid causing influx of water into the airway and reducing the viscoelastic properties of the mucus by breaking some of the mucin bonds&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">As inhalation of hyperosmolar agents may induce airway narrowing and a reduction in FEV1 of about 15&#37; in sensitive subjects&#44; an assessment of bronchial hyperresponsiveness is recommended before starting treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Mannitol</span><p id="par0055" class="elsevierStylePara elsevierViewall">Mannitol is a nonionic sugar alcohol&#44; commonly used as an osmotic agent&#44; which increases mucus clearance&#46; The precise mechanism of this action is unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Studies have demonstrated that the effect of mannitol is acute rather than cumulative but it has a sustained effect for up to 24<span class="elsevierStyleHsp" style=""></span>h&#46; The mucociliary clearance effect was also found in all regions of the lung&#44; including the peripheral region&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Mannitol capsules &#40;40<span class="elsevierStyleHsp" style=""></span>mg&#41; which contain dry powder for inhalation using an inhaler device are commercially available&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> They have been approved for the treatment of CF in adults aged &#8805;18 years&#46; The recommended dose is 400<span class="elsevierStyleHsp" style=""></span>mg &#40;which requires the inhalation of the content of 10 capsules loaded individually into the inhaler&#41; twice a day&#44; once in the morning and once in the evening&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Mannitol has the advantage of being a powder formulation and therefore has a shorter delivery time which avoids the usual maintenance and cleaning issues related with nebulizer devices&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">An international phase-III randomized double-blind placebo-controlled trial of inhaled dry powder mannitol &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#41; was carried out on 324 CF patients&#44; for a 26-week period&#44; twice daily&#46; This showed a significant improvement in FEV1 &#40;change from baseline 118<span class="elsevierStyleHsp" style=""></span>mL &#40;6&#46;5&#37;&#41; <span class="elsevierStyleItalic">versus</span> 26<span class="elsevierStyleHsp" style=""></span>mL &#40;2&#46;4&#37;&#41;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Improvements in FEV1 were seen fairly early &#40;at 6 weeks&#41; and were maintained up to 52 weeks&#46; There was also a 35&#46;4&#37; reduction in the incidence of exacerbation on the mannitol group&#46; It is worth noting that the lung function improvement was found irrespective of the concomitant use of recombinant human deoxyribonuclease &#40;rhDNase&#41;&#46; Cough and haemoptysis were the most common adverse events&#46; Overall they were mild or moderate and only a small proportion of patients had to discontinue the treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Given these results&#44; mannitol was also tested on non-CF BE and even though the first studies were carried out on small groups of patients&#44; during short periods of time and mostly relating to non-clinical issues&#44; they showed promising results of its use in this patient population&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">An open-label study of mannitol &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; carried out on 9 patients with BE&#44; once daily&#44; during a 12-day period documented a highly significant improvement in quality of life&#44; which is assessed by St George&#39;s Respiratory Questionnaire &#40;SGRQ&#41;&#44; and maintained for 6&#8211;10 days after cessation of treatment&#46; It is important to note that patients reported a reduction in cough during both day and night&#44; a reduction of sputum in the morning and an increase in sleeping time&#46; Some properties of sputum were changed&#44; increasing cough efficacy&#46; No significant changes in lung function were found&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A phase-3 multicentre randomized controlled trial&#44; available only in abstract&#44; involving 185 BE patients with mild-to-moderate lung function demonstrated an improvement in health-related quality of life with inhaled mannitol &#40;320<span class="elsevierStyleHsp" style=""></span>mg&#41; over 12 weeks&#46; Furthermore a prolonged time free of antibiotics and a lower total use of antibiotics compared with placebo was observed&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">A phase-III clinical trial is in progress and the purpose of this study is to examine the efficacy and safety of a 52-week treatment with 400<span class="elsevierStyleHsp" style=""></span>mg inhaled mannitol&#44; twice daily&#44; against a control group&#46; The primary outcome measure is the effect of mannitol in reducing the pulmonary exacerbations and the secondary outcomes are the difference in quality of life&#44; antibiotic use&#44; number of hospitalizations&#44; sputum volume&#44; daytime sleepiness scores&#44; lung function and health related costs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Hypertonic saline solution</span><p id="par0085" class="elsevierStylePara elsevierViewall">Hypertonic saline &#40;HS&#41; is an ionic substance quickly transported across the epithelium and delivered using an ultrasonic or jet nebulizer&#46; The highest well tolerated concentration is 7&#37;&#46; Its utility was well documented for CF in a randomized placebo-controlled trial in 164 patients&#44; twice daily&#44; over 48 weeks&#46; The HS group had significantly fewer pulmonary exacerbations&#44; an improvement in quality of life&#44; a reduction in absenteeism from school and work and an improvement in FEV1 of 65<span class="elsevierStyleHsp" style=""></span>ml&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> A Cochrane review in 2009&#44; including 12 trials&#44; concluded that HS is a safe&#44; low-cost and effective therapy in CF&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>However&#44; the HS recommendation for non-CF BE is not clear&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In a crossover trial 24 BE patients&#44; who produced less than 10<span class="elsevierStyleHsp" style=""></span>g of sputum per day&#44; were randomly selected to receive four single treatment schedules once a week&#44; for 4 weeks&#46; This included active cycle breathing technique &#40;ACBT&#41; alone&#59; nebulized terbutaline followed by ACBT after 10<span class="elsevierStyleHsp" style=""></span>min&#59; nebulized terbutaline followed after 10<span class="elsevierStyleHsp" style=""></span>min by nebulized isotonic saline &#40;IS&#41; &#40;09&#37;&#41; then ACBT&#59; nebulized terbutaline followed after 10<span class="elsevierStyleHsp" style=""></span>min by nebulized HS &#40;7&#37;&#41; then ACBT&#46; Both nebulized IS and HS were significantly more effective in increasing sputum yield&#44; reducing sputum viscosity and improving ease of expectoration but HS was significantly better than IS&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In another randomized single blind crossover trial to evaluate IS and HS daily for 3 months in 28 BE patients&#44; a significant improvement in lung function &#40;FEV1 and FVC&#41; and quality of life was documented by changes in global scores and subscales of symptoms and impact of SGRQ in favor of HS&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A recently published research showed different results&#46; Forty patients were randomized to inhale IS or HS 6&#37; daily for 12 months and no important clinical superiority of HS over IS was identified&#46; Nevertheless&#44; there were significant improvements in quality of life&#44; lung function and sputum colonization in both groups&#46; Noteworthy is that prior to the trial 85&#37; of the patients regularly performed airway clearance techniques&#44; which means that the daily use of a saline solution may offer additional benefits&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Even though there is some evidence favoring HS&#44; it seems that both hypertonic and isotonic saline are beneficial in non-CF BE&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21&#44;21</span></a> These results agree with another randomized placebo-controlled study that evaluated the clinical utility of long-term humidification therapy in 108 patients with COPD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#41; or BE &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#46; They used fully humidified high flow air at 37<span class="elsevierStyleHsp" style=""></span>&#176;C through nasal cannulae&#44; daily&#44; over a 12-month period&#46; The patients on long-term humidification therapy showed significantly fewer exacerbation days&#44; increased time to first exacerbation&#44; improvement in quality of life and lung function&#46; There was a non-significant reduction in exacerbation frequency&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">N-acetylcysteine</span><p id="par0110" class="elsevierStylePara elsevierViewall">N-acetylcysteine &#40;NAC&#41; is commonly used in the treatment of BE patients&#46; It is a mucolytic agent that disrupts the disulfide bonds in mucus when inhaled&#46; After oral administration there is no NAC in airway secretions but cysteine is detected in the plasma and induces an increase in glutathione levels in the plasma and lung which has antioxidant properties&#46; Therefore the benefits of this agent may come from its antioxidant properties and not its mucolytic characteristics&#46; NAC has also antibacterial properties by reducing the ability of bacteria to adhere to epithelial cells&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Despite this&#44; in 2001 a Cochrane review concluded that there is no evidence to recommend the use of NAC in non-CF BE&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Sputum clearance is a complex mechanism&#44; with several targets&#44; which is not completely understood&#46; Trials of mucoactive agents are scarce and there are some discordant results&#46; The latter may be explained by the fact that the analyses are usually independent of the underlying disease&#46; With sub-group analyses&#44; clear benefits would probably be discovered&#44; which underlines the importance of defining the etiology&#46; An example of this is the bad results obtained with rhDNase in non-cystic fibrosis BE&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> as it not only failed to improve FEV1 but also the patients got worse&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Anti-inflammatory therapy</span><p id="par0120" class="elsevierStylePara elsevierViewall">As stated before&#44; persistent inflammation is a cardinal feature of BE<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#59; it is part of a vicious cycle which also involves host susceptibility&#44; sputum hypersecretion&#44; airway obstruction and infection&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Sometimes&#44; even in the absence of existing infection there is continuous neutrophilic infiltration of the airways which suggests dysregulation of immune responses&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In this setting&#44; it is reasonable to consider anti-inflammatory and&#47;or immunomodulatory therapies as an option in the management of patients with BE&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Although it is a disease which is increasingly recognized and studied&#44; evidence to support the use of anti-inflammatory therapies is still limited even when taking into account drugs with an established anti-inflammatory role in the treatment of other disorders&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Macrolides</span><p id="par0130" class="elsevierStylePara elsevierViewall">Apart from their antimicrobial activity&#44; macrolides have been increasingly used in clinical practice for the treatment of a variety of chronic pulmonary diseases because of their anti-inflammatory and immune-modulatory properties&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;32</span></a> Although solid evidence to justify long-term macrolide therapy in many of these disorders is still lacking&#44; beneficial effects have been found in small clinical trials of patients with non-CF BE&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#8211;39</span></a> There were considerable variations in the study design of many of these trials&#44; including duration&#44; dose and macrolides tested and outcome measures evaluated but most of them showed consistent evidence of a decrease in sputum volume and some reported a decrease in exacerbation frequency&#46; Several larger studies which have recently been completed corroborate these findings&#46; A significant reduction in exacerbation frequency was found in the preliminary results of a trial with 89 patients which compared the use of azithromycin with a placebo<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> as well as in another study yet to be published with 117 patients using erythromycin&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Accordingly&#44; the largest study to date&#44; which has recently been published&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> demonstrated that a 6 months azithromycin treatment significantly decreased the rate of exacerbations requiring antibiotic therapy&#44; which was sustained for 6 months after completion of treatment&#44; and increased the time to the first exacerbation requiring antibiotics&#46; As well as these beneficial effects&#44; however&#44; it is important to realize that side effects such as gastrointestinal upset&#44; raised transaminase levels&#44; cardiac arrhythmias &#40;particularly prolonged QT interval related&#41;&#44; auditory impairment&#44; urogenital candidiasis and&#44; lastly&#44; and possibly most importantly&#44; the risk of microbial macrolide resistance&#44; particularly non-tuberculous mycobacteria &#40;NMT&#41;&#44; may occur&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;43</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Therefore&#44; macrolides cannot be recommended as routine therapy for non-CF BE before further research is carried out&#44; although their use&#44; particularly azithromycin&#44; can be considered in selected patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;44</span></a> In patients with frequent respiratory exacerbations or continuous symptoms for more than 6 months&#44; particularly if chronically infected with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44; a trial of 3&#8211;6 months of 3 times per week 250&#8211;500<span class="elsevierStyleHsp" style=""></span>mg azithromycin can be done after ruling out NTM infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;44</span></a> Transaminase monitoring should be performed in the first few weeks of treatment and then&#44; as well as NTM screening&#44; every 6 months if there is evidence of benefit to the patient in terms of quality of life and frequency of exacerbations and the therapy is not discontinued&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There are no studies to support either the effectiveness or safety of treatments of more than 12 months duration&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">An overview of the available studies showing the effects of macrolides in patients with BE is presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Corticosteroids</span><p id="par0145" class="elsevierStylePara elsevierViewall">Despite their potent anti-inflammatory action&#44; long-term systemic corticosteroids cannot be used due to potential adverse effects&#46; Inhaled corticosteroids&#44; however&#44; have been studied in patients with BE and a 2009 review by Kapur et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> identified six randomized clinical trials which enrolled 278 of 303 randomized adult patients&#46; This meta-analysis concluded that there was insufficient evidence to recommend the routine use of inhaled steroids in adults with stable state BE but considered that a therapeutic trial might be justified in patients with difficult to control symptoms&#59; these would have to be closely monitored for adverse events especially if high doses were used&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">A recently published Spanish study<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> reported the potentially beneficial effect of the addition of a long acting beta-2 adrenergic to inhaled corticosteroid on clinical parameters and health-related quality of life by allowing the dose of the inhaled steroid to be reduced to half with a reduction of local side effects&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">These findings need to be assessed with larger controlled randomized trials&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Other anti-inflammatory agents</span><p id="par0160" class="elsevierStylePara elsevierViewall">Non-steroidal anti-inflammatory drugs &#40;NSAID&#41; may also be a potentially attractive therapy in patients with BE as ibuprofen has demonstrated beneficial effects on people with CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a> However&#44; two Cochrane Database systemic reviews searching for use of oral<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> and inhaled NSAID<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> in non-CF BE only identified one single trial of inhaled indomethacin <span class="elsevierStyleItalic">versus</span> placebo in 24 adults&#44; 8 of them with BE&#46; This study documented a significant reduction in sputum production and dyspnea in the treatment group over 14 days but further studies on the efficacy of NSAIDs in treating patients with BE are needed&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Like macrolides&#44; another class of drugs that have recognized anti-inflammatory and immunomodulatory properties are hydroxy-methyl-glutaryl-conzymeA reductase inhibitors &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span> statins&#41; which have demonstrated <span class="elsevierStyleItalic">in vitro</span> inhibition of neutrophil migration and epithelial cell production of chemoattractants and proteases and potentiation of macrophage efferocytosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51&#44;52</span></a> As efferocytosis appears to be involved in the pathogenesis of a variety of chronic lung and systemic inflammatory disease including BE&#44; this would seem an attractive target for statins therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> There are currently ongoing clinical trials to evaluate the effect of atorvastatin on patients with BE&#44; with and without <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">54&#44;55</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Leukotriene receptor antagonists may theoretically be of benefit as they inhibit neutrophilic mediated inflammation but there are no controlled studies to date to support their use in BE&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Methylxanthines are also theoretically of use in BE as they are purported to have anti-inflammatory properties but&#44; although there are no published studies to date&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> there are trials currently underway to assess the effect of theophylline in the treatment of bronchiectasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">58&#44;59</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Agents specifically targeting a particular mediator of the immune response might be an interesting new class of drugs in the future&#46; Roflumilast and specific monoclonal antibodies&#44; <span class="elsevierStyleItalic">e&#46;g&#46;</span> against IL-8&#44; matrix metalloproteases &#40;MMPs&#41; or neutrophil elastase&#44; are in this group but the safety and tolerability of these drugs still need to be assessed in phase II and III studies&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Antibiotic therapy</span><p id="par0185" class="elsevierStylePara elsevierViewall">BE provides the perfect environment for colonization by various microorganisms&#44; as mucociliary clearance is impaired&#44; facilitating rapid bacterial growth on the airways mucosal surface without tissue invasion&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In spite of the fact that these bacteria do not cause invasive disease and are usually less virulent than those that invade nearby tissues&#44; they are able to trigger an inflammatory response that aims to eliminate the microorganism&#59; when this purpose fails&#44; however&#44; the inflammation becomes chronic and leads to progressive severe lung injury&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">These pathogens can also develop the means to facilitate their own survival&#44; overcoming host defence mechanisms and antimicrobial actions through biofilm production and other bacterial resistance mechanisms&#46; Thus&#44; the chronic colonization process that occurs in the respiratory tract of patients with BE is called &#8220;pathogenic colonization&#8221;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> and can be divided into three different phases&#58; <span class="elsevierStyleItalic">initial colonization</span> &#40;the first isolate of a microorganism&#41;&#44; <span class="elsevierStyleItalic">intermittent colonization</span> &#40;intermittent isolation of the same microorganism in cultures separated by&#44; at least&#44; a month&#44; representing a chronic colonization process with a low bacterial load&#41; and <span class="elsevierStyleItalic">chronic colonization</span> &#40;three or more successive positive cultures for the same microorganism with&#44; at least&#44; one month apart&#44; within a period of six months&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Exacerbation is a clinical situation that can happen during any of the three scenarios mentioned above&#44; and it has the potential to worsen lung function deterioration&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> The diagnosis of exacerbation in these patients is particularly difficult and is based on the acute development of manifestations such as changes in sputum characteristics &#40;increased volume&#44; purulence and viscosity&#41;&#44; haemoptysis&#44; breathlessness&#44; worsening of cough&#44; chest pain&#44; fever&#44; asthenia&#44; anorexia&#44; weight loss&#44; physical changes in thoracic examination&#44; desaturation&#44; decline in lung function&#44; radiologic signs of lower respiratory tract infection and elevation of systemic biomarkers of inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Several microorganisms can be isolated from the respiratory tract of patients with non-CF BE and the acquisition and clearance of a strain is a complex&#44; dynamic process involving host factors and receptor sites on the organism that may help define its ability to persist and damage airways&#46; There is a slight difference in the dynamics of colonization according to age&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The most frequently isolated pathogens are <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44; <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and <span class="elsevierStyleItalic">Streptococcus pneumonia&#46;</span><a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">61&#44;62</span></a> In children the predominant isolated pathogen is <span class="elsevierStyleItalic">H&#46; influenzae</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#8211;65</span></a> whereas in adults&#44; although <span class="elsevierStyleItalic">H&#46; influenzae</span> is still the most frequently isolated pathogen&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;28&#44;61</span></a> there is a significantly higher isolation rate of <span class="elsevierStyleItalic">P&#46; aeruginosa&#46;</span><a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a><span class="elsevierStyleItalic">S&#46; pneumoniae</span> and <span class="elsevierStyleItalic">Moraxella catharralis</span> are also found in a significant but variable rate and <span class="elsevierStyleItalic">Aspergillus fumigatus</span> is rarely isolated&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> Isolation of <span class="elsevierStyleItalic">Staphylococcus aureus</span> should lead to consideration of underlying CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;26&#44;66</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">P&#46; aeruginosa</span> has a propensity to persist in bronchiectatic airways due to its capacity to produce virulence factors and modulate immune defences by quorum signaling and biofilm production&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Since infection &#40;and particularly <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection&#41; plays a major role in causing and perpetuating BE&#44; reducing the microbial load using antibiotics is a cornerstone of therapy&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> either through treating exacerbations or by using suppressive antibiotic strategies&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">However&#44; the isolation of one or more pathogens in the sputum of patients with non-CF BE is not necessarily an indication for antibiotic treatment&#44; particularly in adults<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a>&#59; there are three main criteria for prescribing antibiotics in this setting&#58; exacerbation&#44; eradication of the first isolate of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and suppressive therapy in steady-state BE chronically colonized with <span class="elsevierStyleItalic">P&#46; aeruginosa&#46;</span></p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Treatment of exacerbations</span><p id="par0230" class="elsevierStylePara elsevierViewall">Early treatment of exacerbations is particularly important as it could probably limit the vicious circle of infection&#47;inflammation that is a determinant factor of lung damage&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The management of these patients includes routine cultures of respiratory secretions to identify infecting organisms and guide antibiotic selection as these patients frequently carry the same bacteria for prolonged periods of time&#46; The current recommendation is to perform cultures every three months on average&#44; so that updated information is available to guide treatment when a pulmonary exacerbation occurs&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Without this information the choice of antibiotic has to be empirical&#44; based on the most common organisms associated with exacerbations in these patients&#44; in particular <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46; Nevertheless&#44; before starting antibiotic therapy&#44; a sputum sample should be sent off for culture&#44; after which antibiotics should be started and then eventually changed in accordance with the microorganism isolated and its antibiogram&#46; However&#44; <span class="elsevierStyleItalic">in vitro</span> antibiotic sensitivity does not always correlate with therapeutic response&#44; which happens with microorganisms able to form a biofilm&#44; where the activity of many antibiotics is diminished&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> So&#44; although an antibiogram is essential for guiding treatment&#44; the value of conventional <span class="elsevierStyleItalic">in vitro</span> susceptibility testing for these patients is being questioned&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">It is also common to isolate more than one microrganism or distinct morphotypes of the same pathogen with the same or different patterns of antimicrobial sensitivity&#46; Selecting an antibiotic combination that covers all the isolates can be difficult without resorting to an impractically large number of antibiotics&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The route of administration will depend on the severity of the exacerbation and the evidence of colonization by multidrug resistant microorganisms&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Mild exacerbations can be treated orally with a fluoroquinolone on an outpatient basis&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">70&#44;71</span></a> The addition of inhaled tobramycin solution &#40;TS&#41; to ciprofloxacin was studied because of concerns regarding virulence and potential resistance of <span class="elsevierStyleItalic">Pseudomonas</span>&#46; In a double-blind&#44; multicenter trial&#44; 53 patients with non-CF BE and respiratory exacerbations due to <span class="elsevierStyleItalic">Pseudomonas</span> were randomly assigned to receive ciprofloxacin plus TS or plus placebo for two weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> The addition of TS did not improve clinical outcomes although there was a marked reduction of <span class="elsevierStyleItalic">Pseudomonas</span> density in the sputum&#46; Based on this&#44; TS cannot be recommended alone or in combination with ciprofloxacin for acute exacerbations in non-CF BE&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Intravenous therapy is reserved for oral therapy failure&#44; severe exacerbations or microorganisms resistant to oral antibiotics&#46; The most commonly selected intravenous regimen combines two antibiotics &#40;usually a &#946;-lactam anti-<span class="elsevierStyleItalic">Pseudomonas</span>&#58; piperacillin-tazobactam&#44; ceftazidime or meropenem&#41; and an aminoglycoside&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#44;70</span></a> The rationale for choosing two rather than one is based on the possibility of obtaining synergic effects and decreasing the risk of antibiotic resistances&#46; Regarding the aminoglycoside&#44; tobramycin is recommended due to its strong activity against <span class="elsevierStyleItalic">P&#46; aeruginosa</span> compared to other aminoglycosides&#46; In cases of tobramycin resistance&#44; amikacin can be used&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Adding an inhaled antibiotic to an intravenous one has not been shown to provide clinical benefits&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">There is no evidence to recommend combination antibiotics in patients colonized with microorganisms other than <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; unless there is more than one pathogen&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Exacerbations should be treated using a high dosage targeted antibiotic therapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> due to the fact that the volume of distribution and total body clearance for hydrophilic drugs &#40;such as aminoglycosides&#44; penicillins&#44; and cephalosporins&#41; are increased because these patients are generally undernourished and have decreased adipose tissue&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">The duration of antibiotic therapy is also a matter of debate requiring further investigation but the expert consensus is that 14 days should be recommended for all exacerbations&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4&#44;60&#44;69</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infection&#47;colonization</span><p id="par0280" class="elsevierStylePara elsevierViewall">As the disease progresses chronic infection by <span class="elsevierStyleItalic">P&#46; aeruginosa</span> becomes common and it seems to be an independent risk factor for accelerated loss of pulmonary function and decreased survival&#46; Conversion of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> to the mucoid phenotype worsens prognosis although it is more common in patients with CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">74&#44;75</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Although there are no studies to guide practice following the <span class="elsevierStyleItalic">first isolation</span>&#44; an attempt to eradicate seems pragmatic for what it should be treated aggressively regardless of the patient&#39;s clinical signs or symptoms in order to eliminate the microorganism from the sputum as it is very difficult to do so once chronic colonization is established&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">In non-CF BE the strategy proposed for eradication is oral ciprofloxacin for 3 weeks and if it fails&#44; the same protocol as for CF is recommended &#40;nebulized antibiotic&#58; tobramycin&#44; sodium colistimethate or aztreonam lysine&#41; plus oral ciprofloxacin for 3 weeks&#44; followed by inhaled antibiotics for 3&#8211;12 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;60&#44;76</span></a> An alternative would be an association of 2 anti-<span class="elsevierStyleItalic">Pseudomonas</span> intravenous antibiotics for 14&#8211;21 days&#44; followed by an inhaled antibiotic for 3&#8211;12 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;60&#44;76</span></a> As was stated above&#44; an antibiogram is essential for guiding treatment although it is recognized that <span class="elsevierStyleItalic">in vitro</span> sensitivity does not always correlate with therapeutic response&#46; However&#44; for nebulized antibiotics the interpretation of the antibiogram should take into consideration that&#44; through this form of delivery&#44; antibiotic achieves much higher concentrations in the bronchial mucosa overcoming the mechanisms of resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">The persistence of bacteria despite aggressive treatment is thought to be due to several factors such as poor penetration of antibiotics into purulent airway secretions&#44; native or acquired antibiotic resistance and production of biofilms by the bacteria that may render antibiotics ineffective or interfere with host defences&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">To prevent the decline in lung function associated to chronic bronchial colonization with this pathogen&#44; nebulized antibiotics that show <span class="elsevierStyleItalic">in vitro</span> activity against <span class="elsevierStyleItalic">P&#46; aeruginosa</span> are frequently used as chronic suppressive therapy&#46; The aim of this strategy is to reduce the bacterial burden &#40;as in this phase it is virtually impossible to eradicate the pathogen&#41; and&#44; thus&#44; reduce the inflammatory response that leads to structural lung damage and loss of function&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;78</span></a> avoiding the cumbersome and toxic iatrogenic effects associated to oral or intravenous route&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a> It seems that this strategy may reduce the frequency and severity of respiratory exacerbations and the decline in lung function&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">80&#44;81</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">One trial conducted in 2000 randomly assigned 74 patients with non-CF BE and <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection to receive aerosolized tobramycin &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#44; twice daily&#41; or aerosolized placebo for 28 days&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> Patients in the treatment group demonstrated a 10&#44;000-fold reduction in <span class="elsevierStyleItalic">Pseudomonas</span> density&#44; but no change in FEV1 as compared to controls&#46; The same results were attained in a similar trial conducted in 2001&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">In 2005&#44; a 6 month double blind crossover study of aerosol tobramycin was carried out on 30 patients and revealed no change in exacerbation rate&#44; but the number of hospitalizations and duration of hospital stay were reduced during the tobramycin phase&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">In 2005 a smaller uncontrolled study was carried out in which aerosolized tobramycin &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#44; twice daily&#41; was administered to 41 patients with non-CF BE and <span class="elsevierStyleItalic">Pseudomonas</span> infection&#59; the protocol alternated two weeks with therapy and two weeks without&#44; for a total of 12 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a> Treatment was associated with a decrease in symptoms and improvements in health-related quality of life &#40;QOL&#41;&#46; However&#44; 10 of 41 patients were unable to complete the protocol because of side effects &#40;cough&#44; wheezing or worsened dyspnea&#41;&#44; and two of the patients who completed the trial acquired tobramycin-resistant <span class="elsevierStyleItalic">Pseudomonas</span> species&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">In 2007 an uncontrolled study examined the efficacy of nebulized colistin in a mixed population of patients with COPD and bronchiectasis colonized with PSAE and showed an improvement in quality of life and slower decline with FEV1 with treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">Currently&#44; many other clinical trials are being carried out with the purpose of establishing the indications for inhaled antibiotic therapy in these patients and define which antibiotics to use and the most appropriate devices to deliver them&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">In fact&#44; at the moment&#44; the clinical evidence that supports the use of chronic inhaled antibiotherapy in non-CF BE&#44; chronically colonized with <span class="elsevierStyleItalic">Pseudomonas</span>&#44; is scarce but all the data suggest that this therapeutic strategy seems to control the symptoms&#44; prevent the progression of the disease and reduce the morbidity with no relevant adverse events&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">87&#44;88</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">The chronic antibiotherapy may be intermittent &#40;28 days <span class="elsevierStyleItalic">on</span>&#44; 28 days <span class="elsevierStyleItalic">off</span>&#41; when using tobramycin or aztreonam lysine or continuous when using sodium colistimethate&#46; However&#44; continuous inhaled antibiotherapy should be prescribed using 2 different antibiotics alternately in patients that are very symptomatic in <span class="elsevierStyleItalic">off</span>-periods&#44; or with severe lung function impairment or recurrent pulmonary exacerbations despite taking one antibiotic every other month&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">Nevertheless&#44; there is still a degree of uncertainty about when to prescribe the various inhaled antibiotics and what to choose&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">At the moment the recommendations<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> are to treat patients with non-CF BE chronically colonized with <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and with frequent acute exacerbations &#40;three or more per year&#41; or progressive deterioration of lung function&#44; with inhaled antibiotics&#59; it seems reasonable to use tobramycin as the first choice because of the extensive information supporting its efficacy and good safety record after many years of use&#46; The level of evidence and clinical benefit is greatest for patients with moderate or severe lung disease&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">The option for inhaled aztreonam instead of tobramycin may be considered if there is evidence of inhaled tobramycin intolerance&#44; clinical deterioration despite inhaled tobramycin&#44; a strong possibility of increasing adherence due to the fact that inhaled aztreonam can be delivered more rapidly than tobramycin and evidence or possibility of pregnancy when aminoglycosides are relatively contraindicated&#46; Data are needed from well-designed comparative effectiveness trials for tobramycin and aztreonam to provide for a more informed decision as to which to use&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Given the less than robust data supporting its use and the suggestion that it may be inferior&#44; it seems reasonable to prescribe colistin only in cases of tobramycin therapeutic failure or intolerance&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">In conclusion&#44; controlling respiratory infection&#47;colonization is the cornerstone of therapy in non-CF BE with a significant impact on survival for which more robust data are needed to support decisions in this area&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion</span><p id="par0365" class="elsevierStylePara elsevierViewall">BE has recently became a hot topic&#46; First results of well designed trials have been published and several studies are in progress&#46; However&#44; there are many questions regarding treatment which are still waiting for scientific answers&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">It will be important to design studies involving a greater number of patients&#44; with different levels of severity&#44; more specific aetiological information and carried out over longer time periods to clarify the real benefits of these promising therapies and bring new insights into this interesting topic&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical disclosures</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of human and animal subjects</span><p id="par0375" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Confidentiality of data</span><p id="par0380" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0385" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0390" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres547681"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec565561"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres547680"
          "titulo" => "Resumo"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec565560"
          "titulo" => "Palavras-chave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Mucoactive therapy"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Mannitol"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Hypertonic saline solution"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "N-acetylcysteine"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Anti-inflammatory therapy"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Macrolides"
            ]
            1 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Corticosteroids"
            ]
            2 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Other anti-inflammatory agents"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0050"
          "titulo" => "Antibiotic therapy"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Treatment of exacerbations"
            ]
            1 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Treatment of Pseudomonas aeruginosa infection&#47;colonization"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclusion"
        ]
        9 => array:3 [
          "identificador" => "sec0070"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflicts of interest"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-03-17"
    "fechaAceptado" => "2013-03-21"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec565561"
          "palabras" => array:6 [
            0 => "Non-cystic fibrosis bronchiectasis"
            1 => "Advances"
            2 => "Mucoactive"
            3 => "Anti-inflammatory"
            4 => "Antibiotic"
            5 => "Therapy"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec565560"
          "palabras" => array:6 [
            0 => "Bronquiectasia n&#227;o-fibrose c&#237;stica"
            1 => "Avan&#231;os"
            2 => "Mucoactivo"
            3 => "Anti-inflamat&#243;rio"
            4 => "Antibi&#243;tico"
            5 => "Terapia"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Non-cystic fibrosis bronchiectasis remains a common and important respiratory disease to date&#46; It is a chronic pathology and consequently the patients usually require continuous treatment&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In recent decades therapies that do not have scientific evidence of their benefits have been commonly used in non-cystic fibrosis bronchiectasis&#46; Cystic fibrosis has provided the experience to extrapolate therapeutic approaches to other bronchiectasis patients&#46; Finally&#44; in the last few years some trials have been carried out specifically in non-cystic fibrosis bronchiectasis which aim to assess the efficacy of some of the treatments which are commonly used but sometimes without clear indication&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This review will discuss the recent results from these trials&#44; namely mucoactive&#44; anti-inflammatory and antibiotic therapy&#46; Several trials are ongoing and we hope they will be able to add clarification to the management of these patients&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As bronquiectasias n&#227;o-fibrose qu&#237;stica continuam a ser uma doen&#231;a respirat&#243;ria comum e importante&#46; Trata-se de uma patologia cr&#243;nica e&#44; consequentemente&#44; os doentes geralmente precisam de um tratamento cont&#237;nuo&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Nas &#250;ltimas d&#233;cadas&#44; tratamentos sem evid&#234;ncia cient&#237;fica dos seus benef&#237;cios foram comumente usadas nas bronquiectasias n&#227;o-fibrose qu&#237;stica&#46; A fibrose qu&#237;stica serviu de experi&#234;ncia para extrapolar a abordagem terap&#234;utica para outros doentes com bronquiectasias&#46; Finalmente&#44; nos &#250;ltimos anos&#44; foram realizados alguns ensaios bronquiectasias n&#227;o-fibrose qu&#237;stica que visam avaliar a efic&#225;cia de alguns dos tratamentos que s&#227;o comummente usados mas por vezes sem uma clara indica&#231;&#227;o&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Nesta revis&#227;o ser&#227;o apresentados os resultados recentes destes ensaios&#44; nomeadamente sobre o tratamento mucoactivo&#44; anti-inflamat&#243;rio e antibi&#243;tico&#46; Diversos estudos est&#227;o a decorrer e esperamos que estes venham a esclarecer a abordagem mais adequada destes doentes&#46;</p></span>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hyperosmolar agent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mannitol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hypertonic saline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400<span class="elsevierStyleHsp" style=""></span>mg bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 or 7&#37; bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Delivery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">By an inhaler&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">By nebulizer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Duration of effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sustained &#40;up to 24<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Short&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab884635.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Comparison between mannitol and hypertonic saline&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">BAT</span>&#58; Bronchiectasis and long-term Azithromycin Treatment&#59; <span class="elsevierStyleItalic">BLESS</span>&#58; Bronchiectasis and Low-dose Erythromycin Study&#59; <span class="elsevierStyleItalic">EMBRACE</span>&#58; Effectiveness of Macrolides in patients with BRonchiectasis using Azithromycin to Control Exacerbations&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&#59;Mean age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&#47;dosageMean duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Benefits&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse effects &#40;number of patients&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Koh et al&#46; &#40;1997&#41;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#59;13 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Roxithromycin&#58; 4<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#59;12 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Airway hyperresponsiveness&#8595; sputum purulence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not studied&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Tsang et al&#46; &#40;1999&#41;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#59;54&#46;3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Erythromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#59;8 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; EV<span class="elsevierStyleInf">1</span> and FVC&#59;&#8595; sputum volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rash &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Davies et al&#46; &#40;2004&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prospective&#44;open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39&#59;51&#46;9 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day 6 days&#44; followed by 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 6 days and later 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 3 days&#47;week&#59;&#62;4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Volume of sputum&#8595; Symptoms&#8595; Exacerbations&#8593; DLCO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea &#40;2&#41;&#59;abnormal liver function tests &#40;2&#41;&#59;rash &#40;1&#41;&#59;tinnitus &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Cymbala et al&#46; &#40;2005&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;open label&#44;crossover&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#59;71 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 2 days&#47;week&#59;6 months<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Volume of sputum&#8595; Exacerbations&#8593; General well-being&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Yalcin et al&#46; &#40;2006&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34&#59;12&#46;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clarithromycin&#58; 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#59;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; FEF<span class="elsevierStyleInf">25&#8211;75</span>&#8595; Volume of sputum&#8595; Inflammatory markers in BAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Anwar et al&#46; &#40;2008&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Retrospective&#44;open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#59;63 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 3 days&#47;week&#59;9&#46;1 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; FEV<span class="elsevierStyleInf">1</span>&#8595; Exacerbations&#8595; Sputum microbial isolates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea &#40;3&#41;abdominal cramps &#40;2&#41;&#59;skin rash &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Serisier et al&#46; &#40;2011&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prospective&#44;open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#59;62&#46;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Erythromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#59;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Exacerbations&#8595; Annual days of antibiotic use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nausea &#40;1&#41;Headache &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Alternburg et al&#46; &#40;2011&#41;BAT<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">89&#59;65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#59;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Exacerbations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Serisier et al&#46; &#40;2012&#41;BLESS<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#59;62&#46;3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Erythromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#59;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Exacerbations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">QTc prolongation &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Wong et al&#46; &#40;2012&#41;EMBRACE<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">141&#59;60 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 3 days&#47;week&#59;6 months<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>6 months follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Rate of exacerbations&#8593; Time to first exacerbation&#8595; Blood neutrophils&#44; WBC and eosinophils&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Macrolide resistant <span class="elsevierStyleItalic">S&#46; pneumonia</span> &#40;2&#41;Gastrointestinal symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab884634.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Clinical trials of macrolide therapy&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:88 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;A&#46; Floto"
                            1 => "C&#46;S&#46; Haworth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Eur Respir Mon"
                        "fecha" => "2011"
                        "paginaInicial" => "52"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;L&#46; Metersky"
                            1 => "A&#46;E&#46; O&#8217;Donnel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Clin Chest Med"
                        "fecha" => "2012"
                        "paginaInicial" => "33"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "British Thoracic Society guideline for non-CF bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;C&#46; Pasteur"
                            1 => "D&#46; Bilton"
                            2 => "A&#46;T&#46; Hill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2010.136119"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2010"
                        "volumen" => "65"
                        "paginaInicial" => "i1"
                        "paginaFinal" => "i58"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20627931"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis and Treatment of Bronchiectasis&#46; Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Vendrell"
                            1 => "J&#46; De Gracia"
                            2 => "C&#46; Oliveira"
                            3 => "M&#46;A&#46; Mart&#237;nez"
                            4 => "R&#46; Gir&#243;n"
                            5 => "L&#46; M&#225;iz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2008"
                        "volumen" => "44"
                        "paginaInicial" => "629"
                        "paginaFinal" => "640"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19007570"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Evaluating success of therapy for bronchiectasis&#46; What end points to use&#63;"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ccm.2012.03.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chest Med"
                        "fecha" => "2012"
                        "volumen" => "33"
                        "paginaInicial" => "329"
                        "paginaFinal" => "349"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22640849"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucins&#44; mucus&#44; and sputum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;A&#46; Voynow"
                            1 => "B&#46;K&#46; Rubin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.08-0412"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2009"
                        "volumen" => "135"
                        "paginaInicial" => "505"
                        "paginaFinal" => "512"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19201713"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucoactive agents for airway mucus hypersecretory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46; Rogers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Care"
                        "fecha" => "2007"
                        "volumen" => "52"
                        "paginaInicial" => "1176"
                        "paginaFinal" => "1198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17716385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New concepts of the pathogenesis of cystic fibrosis lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;C&#46; Boucher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2004"
                        "volumen" => "23"
                        "paginaInicial" => "146"
                        "paginaFinal" => "158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14738247"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0016508597001273"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis&#58; effect on lung function&#44; health status and sputum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Daviskas"
                            1 => "S&#46;D&#46; Anderson"
                            2 => "K&#46; Gomes"
                            3 => "P&#46; Briffa"
                            4 => "B&#46; Cochrane"
                            5 => "H&#46;K&#46; Chan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1843.2005.00659.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respirology"
                        "fecha" => "2005"
                        "volumen" => "10"
                        "paginaInicial" => "46"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15691238"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46;T&#46; King"
                            1 => "E&#46; Daviskas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Breathe"
                        "fecha" => "2010"
                        "volumen" => "6"
                        "paginaInicial" => "353"
                        "paginaFinal" => "360"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled mannitol in the treatment of non-cystic fibrosis bronchiectasis in adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Gjoerup"
                            1 => "O&#46; Hilberg"
                            2 => "E&#46; Bendstrup"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1843.2012.02189.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respirology"
                        "fecha" => "2012"
                        "volumen" => "17"
                        "paginaInicial" => "927"
                        "paginaFinal" => "932"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22564014"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Bronchitol<span class="elsevierStyleSup">&#174;</span> Pharmaxis Pharmaceuticals Ltd&#46; European Medicines Agency"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Daviskas"
                            1 => "S&#46;D&#46; Anderson"
                            2 => "S&#46; Eberl"
                            3 => "H&#46;K&#46; Chan"
                            4 => "I&#46;H&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2001"
                        "volumen" => "119"
                        "paginaInicial" => "414"
                        "paginaFinal" => "421"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11171717"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled dry-powder mannitol in cystic fibrosis&#58; an efficacy and safety study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "D&#46; Bilton"
                            1 => "P&#46; Robinson"
                            2 => "P&#46; Cooper"
                            3 => "C&#46;G&#46; Gallagher"
                            4 => "J&#46; Kolbe"
                            5 => "H&#46; Fox"
                            6 => "CF301 Study Investigators"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00187510"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2011"
                        "volumen" => "38"
                        "paginaInicial" => "1071"
                        "paginaFinal" => "1080"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21478216"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized placebo-controlled trial of inhaled mannitol in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Bilton"
                            1 => "E&#46; Daviskas"
                            2 => "A&#46; Jacques"
                            3 => "S&#46;D&#46; Anderson"
                            4 => "B&#46; Charlton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "179"
                        "paginaInicial" => "A3221"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "A Phase III Multicenter&#44; Randomized&#44; Parallel Group&#44; Controlled&#44; Double Blind Study to Investigate the Safety and Efficacy of Inhaled Mannitol Over 12 Months in the Treatment of Bronchiectasis"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Elkins"
                            1 => "M&#46; Robinson"
                            2 => "B&#46;R&#46; Rose"
                            3 => "C&#46; Harbour"
                            4 => "C&#46;P&#46; Moriarty"
                            5 => "B&#46; Guy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa043900"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "229"
                        "paginaFinal" => "240"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16421364"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nebulised hypertonic saline for cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Wark"
                            1 => "V&#46;M&#46; McDonld"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD001506.pub3"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2009"
                        "volumen" => "2"
                        "paginaInicial" => "CD001506"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19370568"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of nebulised hypertonic saline &#40;7&#37;&#41; as an adjunct to physiotherapy in patients with stable bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46; Kellet"
                            1 => "J&#46; Redfern"
                            2 => "R&#46; Mcl Niven"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2005"
                        "volumen" => "99"
                        "paginaInicial" => "27"
                        "paginaFinal" => "31"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15672845"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nebulised 7&#37; hypertonic saline improves lung function and quality of life in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Kellet"
                            1 => "N&#46;M&#46; Robert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2011.07.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2011"
                        "volumen" => "105"
                        "paginaInicial" => "1831"
                        "paginaFinal" => "1835"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22018993"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The long term effect of inhaled hypertonic saline 6&#37; in non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;H&#46;H&#46; Nicolson"
                            1 => "R&#46;G&#46; Stirling"
                            2 => "B&#46;M&#46; Borg"
                            3 => "B&#46;M&#46; Button"
                            4 => "J&#46;W&#46; Wilson"
                            5 => "A&#46;E&#46; Holland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2011.12.021"
                      "Revista" => array:7 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2012"
                        "volumen" => "106"
                        "paginaInicial" => "661"
                        "paginaFinal" => "667"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22349069"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673605663787"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical utility of long-term humidification therapy in chronic airway disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Rea"
                            1 => "S&#46; McAuley"
                            2 => "L&#46; Jayaram"
                            3 => "J&#46; Garrett"
                            4 => "H&#46; Hockey"
                            5 => "L&#46; Storey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2009.12.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2010"
                        "volumen" => "104"
                        "paginaInicial" => "525"
                        "paginaFinal" => "533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20144858"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucoactive agents for airway mucus hypersecretory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;F&#46; Rogers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Care"
                        "fecha" => "2007"
                        "volumen" => "52"
                        "paginaInicial" => "1176"
                        "paginaFinal" => "1197"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17716385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucolytics for bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;J&#46; Crockett"
                            1 => "J&#46;M&#46; Cranston"
                            2 => "K&#46;M&#46; Latimer"
                            3 => "K&#46;M&#46; Latiner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD001289"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2001"
                        "volumen" => "1"
                        "paginaInicial" => "CD001289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11279712"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;E&#46; O&#8217;Donnel"
                            1 => "A&#46;F&#46; Barker"
                            2 => "J&#46;S&#46; Ilowite"
                            3 => "R&#46;B&#46; Fick"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1998"
                        "volumen" => "113"
                        "paginaInicial" => "1329"
                        "paginaFinal" => "1334"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9596315"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;E&#46; O&#8217;Donnell"
                            1 => "Bronchiectasis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.08-0776"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2008"
                        "volumen" => "134"
                        "paginaInicial" => "815"
                        "paginaFinal" => "823"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18842914"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammation&#58; a two-edged sword&#8212;the model of bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;J&#46; Cole"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Respir Dis Suppl"
                        "fecha" => "1986"
                        "volumen" => "147"
                        "paginaInicial" => "6"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3533593"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchial inflammation and colonization in patients with clinically stable bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Angrill"
                            1 => "R&#46; de Celis"
                            2 => "F&#46; Arancibia"
                            3 => "X&#46; Filella"
                            4 => "A&#46; Ra&#241;&#243;"
                            5 => "M&#46; Elena"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.164.9.2105083"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2001"
                        "volumen" => "164"
                        "paginaInicial" => "1628"
                        "paginaFinal" => "1632"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11719301"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunomodulatory effects of macrolide antibiotics&#8212;Part 1&#58; Biological mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Altenburg"
                            1 => "C&#46;S&#46; De Graaff"
                            2 => "T&#46;S&#46; Van der Werf"
                            3 => "W&#46;G&#46; Boersma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000320319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respiration"
                        "fecha" => "2011"
                        "volumen" => "81"
                        "paginaInicial" => "67"
                        "paginaFinal" => "74"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20733281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunomodulatory effects of macrolide antibiotics&#8212;Part 2&#58; Advantages and disadvantages of long-term&#44; low-dose macrolide therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Altenburg"
                            1 => "C&#46;S&#46; De Graaff"
                            2 => "T&#46;S&#46; Van der Werf"
                            3 => "W&#46;G&#46; Boersma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000320320"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respiration"
                        "fecha" => "2011"
                        "volumen" => "81"
                        "paginaInicial" => "75"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20733282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Macrolides beyond the conventional antimicrobials&#58; a class of potent immunomodulators"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "E&#46;J&#46; Giamarellos-Bourboulis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijantimicag.2007.08.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Antimicrob Agents"
                        "fecha" => "2008"
                        "volumen" => "31"
                        "paginaInicial" => "12"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17935949"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Usefulness of macrolides as anti-inflammatories in respiratory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46; Sevilla-S&#225;nchez"
                            1 => "D&#46; Soy-Muner"
                            2 => "N&#46; Soler-Porcar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arbres.2009.10.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2010"
                        "volumen" => "46"
                        "paginaInicial" => "244"
                        "paginaFinal" => "254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19962815"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of roxithromycin on airway responsiveness in children with bronchiectasis&#58; a double-blind&#44; placebo-controlled study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Y&#46;Y&#46; Koh"
                            1 => "M&#46;H&#46; Lee"
                            2 => "Y&#46;H&#46; Sun"
                            3 => "K&#46;W&#46; Sung"
                            4 => "J&#46;H&#46; Chae"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1997"
                        "volumen" => "10"
                        "paginaInicial" => "994"
                        "paginaFinal" => "999"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9163637"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pilot study of low-dose erythromycin in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;W&#46; Tsang"
                            1 => "P&#46;I&#46; Ho"
                            2 => "K&#46;N&#46; Chan"
                            3 => "M&#46;S&#46;M&#46; Ip"
                            4 => "W&#46;K&#46; Lam"
                            5 => "C&#46;S&#46; Ho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "13"
                        "paginaInicial" => "361"
                        "paginaFinal" => "364"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10065682"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prophylactic antibiotic treatment of bronchiectasis with azithromycin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Davies"
                            1 => "R&#46; Wilson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "540"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15170048"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;A&#46; Cymbala"
                            1 => "L&#46;C&#46; Edmonds"
                            2 => "M&#46;A&#46; Bauer"
                            3 => "P&#46;J&#46; Jederlinic"
                            4 => "J&#46;J&#46; May"
                            5 => "J&#46;M&#46; Victory"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Treat Respir Med"
                        "fecha" => "2005"
                        "volumen" => "4"
                        "paginaInicial" => "117"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15813663"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Yalcin"
                            1 => "N&#46; Kiper"
                            2 => "U&#46; Ozcelik"
                            3 => "D&#46; Do&#287;ru"
                            4 => "P&#46; F&#305;rat"
                            5 => "A&#46; &#350;ahin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2710.2006.00708.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Pharm Ther"
                        "fecha" => "2006"
                        "volumen" => "31"
                        "paginaInicial" => "49"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16476120"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46;A&#46; Anwar"
                            1 => "S&#46;C&#46; Bourke"
                            2 => "G&#46; Afolabi"
                            3 => "P&#46; Middleton"
                            4 => "C&#46; Ward"
                            5 => "R&#46;M&#46; Rutherford"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2008.06.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2008"
                        "volumen" => "102"
                        "paginaInicial" => "1494"
                        "paginaFinal" => "1496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18653323"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term&#44; low-dose erythromycin in bronchiectasis subjects with frequent infective exacerbations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;J&#46; Serisier"
                            1 => "M&#46;L&#46; Martin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2011.01.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2011"
                        "volumen" => "105"
                        "paginaInicial" => "946"
                        "paginaFinal" => "949"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21367595"
                             …1
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term azithromycin treatment&#58; a randomized placebo-controlled trial in non-CF bronchiectasis&#59; results from the BAT trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2011"
                        "volumen" => "36"
                        "numero" => "Suppl&#46; 54"
                        "paginaInicial" => "333s"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Bronchiectasis and Low-dose Erythromycin Study &#40;BLESS&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2012"
                        "volumen" => "185"
                        "numero" => "May &#40;1 Meeting Abstracts&#41;"
                        "paginaInicial" => "A68624"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis &#40;EMBRACE&#41;&#58; a randomised&#44; double-blind&#44; placebo-controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)60953-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "380"
                        "paginaInicial" => "660"
                        "paginaFinal" => "667"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arbres.2011.06.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2011"
                        "volumen" => "47"
                        "paginaInicial" => "599"
                        "paginaFinal" => "609"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Med J Aust"
                        "fecha" => "2010"
                        "volumen" => "193"
                        "paginaInicial" => "356"
                        "paginaFinal" => "365"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled steroids for bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD000996.pub2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2009"
                        "volumen" => "1"
                        "paginaInicial" => "CD000996"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical efficacy and safety of budesonide-formoterol in non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.11-0180"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2012"
                        "volumen" => "141"
                        "paginaInicial" => "461"
                        "paginaFinal" => "468"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of high-dose ibuprofen in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199503303321303"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1995"
                        "volumen" => "332"
                        "paginaInicial" => "848"
                        "paginaFinal" => "854"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD001505.pub2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                        "volumen" => "4"
                        "paginaInicial" => "CD001505"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral non steroid anti-inflammatories for children and adults with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD006427.pub2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                        "volumen" => "4"
                        "paginaInicial" => "CD006427"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled non-steroid anti-inflammatories for children and adults with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD007525.pub2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2010"
                        "volumen" => "4"
                        "paginaInicial" => "CD007525"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0016508502334140"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pharmthera.2009.06.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacol Ther"
                        "fecha" => "2009"
                        "volumen" => "124"
                        "paginaInicial" => "86"
                        "paginaFinal" => "95"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lovastatin enhances clearance of apoptotic cells &#40;efferocytosis&#41; with implications for chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2006"
                        "volumen" => "176"
                        "paginaInicial" => "7657"
                        "paginaFinal" => "7665"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Burying the dead&#58; the impact of failed apoptotic cell removal &#40;efferocytosis&#41; on chronic inflammatory lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.129.6.1673"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2006"
                        "volumen" => "129"
                        "paginaInicial" => "1673"
                        "paginaFinal" => "1682"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Atorvastatin in bronchiectasis in patients with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "A trial of atorvastatin as an anti-inflammatory agent in non-cystic fibrosis bronchiectasis"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leukotriene receptor antagonists for non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2000"
                        "paginaInicial" => "CD002174"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral methylxanthines for bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2001"
                        "paginaInicial" => "CD002734"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "The effect of theophylline in the treatment of bronchiectasis"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "The role of theophylline plus low-dose formoterol-budesonide in treatment of bronchiectasis&#46; ClinicalTrials&#46;gov&#46; Trial identifier&#58; <a href="ctgov:NCT01769898">NCT01769898</a>&#46;"
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobial therapy for pulmonar pathogenic colonisation and infection by <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in cystic fibrosis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1469-0691.2005.01217.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Microbiol Infect"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "paginaInicial" => "690"
                        "paginaFinal" => "703"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bacterial colonisation in patients with bronchiectasis&#58; microbiological pattern and risk factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2002"
                        "volumen" => "57"
                        "paginaInicial" => "15"
                        "paginaFinal" => "19"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An investigation into causative factors in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.162.4.9906120"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "162"
                        "paginaInicial" => "1277"
                        "paginaFinal" => "1284"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2002"
                        "volumen" => "57"
                        "paginaInicial" => "935"
                        "paginaFinal" => "938"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paediatric bronchiectasis in the twenty-first century&#58; experience of a tertiary children&#39;s hospital in New Zealand"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Paediatr Child Health"
                        "fecha" => "2003"
                        "volumen" => "39"
                        "paginaInicial" => "111"
                        "paginaFinal" => "117"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The need to redefine non-cystic fibrosis bronchiectasis in childhood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "324"
                        "paginaFinal" => "327"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determinants of chronic infection with <span class="elsevierStyleItalic">Staphylococcus aureus</span> in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "14"
                        "paginaInicial" => "1340"
                        "paginaFinal" => "1344"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathogen&#8211;host interactions in <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> pneumonia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200408-1044SO"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "171"
                        "paginaInicial" => "1209"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neutrophil apoptosis&#44; proinflammatory mediators and cell counts in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "231"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differences in biofilm development and antibiotic susceptibility among <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> isolates from cystic fibrosis samples and blood cultures"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jac/dkl482"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Antimicrob Chemother"
                        "fecha" => "2007"
                        "volumen" => "59"
                        "paginaInicial" => "301"
                        "paginaFinal" => "304"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Normativa del diagn&#243;stico y el tratamento de la afecci&#243;n respirat&#243;ria en la fibrosis qu&#237;stica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2001"
                        "volumen" => "37"
                        "paginaInicial" => "316"
                        "paginaFinal" => "324"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparative study on the efficacy of levofloxacin and ceftazidime in acute exacerbation of bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "14"
                        "paginaInicial" => "1206"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infection in adult bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.130.5.1503"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2006"
                        "volumen" => "130"
                        "paginaInicial" => "1503"
                        "paginaFinal" => "1510"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra012519"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2002"
                        "volumen" => "346"
                        "paginaInicial" => "1383"
                        "paginaFinal" => "1393"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.07-0490"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2007"
                        "volumen" => "132"
                        "paginaInicial" => "1565"
                        "paginaFinal" => "1572"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of PSAE infection on clinical parameters in steady-state bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1998"
                        "volumen" => "114"
                        "paginaInicial" => "1594"
                        "paginaFinal" => "1598"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antibiotic strategies for eradicating <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in people with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2006"
                        "paginaInicial" => "CD001392"
                        "itemHostRev" => array:3 [
                          "pii" => "S001650850701918X"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breakpoints for predicting <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> susceptibility to inhaled tobramycin in cystic fibrosis patients&#58; use of high-range Etest strips"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.43.9.4480-4485.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2005"
                        "volumen" => "43"
                        "paginaInicial" => "4480"
                        "paginaFinal" => "4485"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prolonged antibiotics for purulent bronchiectasis in children and adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                        "paginaInicial" => "CD001392"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Utilidad de los antibi&#243;ticos inalados&#58; m&#225;s all&#225; de la fibrosis qu&#237;stica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Neumol Pediatr"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "119"
                        "paginaFinal" => "122"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tobramycin solution for inhalation reduces sputum <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> density in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.162.2.9910086"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "162"
                        "paginaInicial" => "481"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201005-0756OC"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2011"
                        "volumen" => "183"
                        "paginaInicial" => "491"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment with tobramycin solution for inhalation in bronchiectasis with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2001"
                        "volumen" => "120"
                        "paginaInicial" => "114s"
                        "paginaFinal" => "117s"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1345/aph.1E099"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Pharmacother"
                        "fecha" => "2005"
                        "volumen" => "39"
                        "paginaInicial" => "39"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.127.4.1420"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2005"
                        "volumen" => "127"
                        "paginaInicial" => "1420"
                        "paginaFinal" => "1426"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of long term nebulized colistin on lung function and quality of life in patients with chronic bronchial sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1445-5994.2007.01404.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intern Med J"
                        "fecha" => "2007"
                        "volumen" => "37"
                        "paginaInicial" => "495"
                        "paginaFinal" => "498"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled liposomal ciprofloxacin hydrochloride significantly reduces sputum <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> density in CF and non-CF bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "179"
                        "paginaInicial" => "A3214"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de las bronquiectasias no debidas a fibrosis qu&#237;stica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arbres.2011.06.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2011"
                        "volumen" => "47"
                        "paginaInicial" => "599"
                        "paginaFinal" => "609"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de las bronchiectasias no fibrosis qu&#237;stica en fase estable"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Neumosur"
                        "fecha" => "2006"
                        "volumen" => "18"
                        "paginaInicial" => "143"
                        "paginaFinal" => "150"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/08732159/0000001900000006/v2_201509041406/S0873215913000536/v2_201509041406/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "9597"
    "tipo" => "SECCION"
    "pt" => array:2 [
      "titulo" => "Revis&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "pt"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/08732159/0000001900000006/v2_201509041406/S0873215913000536/v2_201509041406/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215913000536?idApp=UINPBA00004E"
]
Share
Journal Information

Statistics

Follow this link to access the full text of the article

Review
New advances in the therapy of non-cystic fibrosis bronchiectasis
Novos avanços no tratamento da Bronquiectasia não-fibrose cística
A. Amorima,
Corresponding author
adelinamorim@gmail.com

Corresponding author.
, F. Gamboab, P. Azevedoc
a Pneumology Department, Centro Hospitalar São João, EPE, Faculty of Medicine, University of Porto, Porto, Portugal
b Pneumology Department, Centro Hospitalar e Universitário de Coimbra-Hospitais da Universidade de Coimbra, EPE, Coimbra, Portugal
c Pneumology Department, Centro Hospitalar Santa Maria, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Read
30515
Times
was read the article
4484
Total PDF
26031
Total HTML
Share statistics
 array:24 [
  "pii" => "S0873215913000536"
  "issn" => "08732159"
  "doi" => "10.1016/j.rppneu.2013.03.006"
  "estado" => "S300"
  "fechaPublicacion" => "2013-11-01"
  "aid" => "155"
  "copyright" => "Sociedade Portuguesa de Pneumologia"
  "copyrightAnyo" => "2013"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "ssu"
  "cita" => "Rev Port Pneumol. 2013;19:266-75"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 24252
    "formatos" => array:3 [
      "EPUB" => 302
      "HTML" => 21216
      "PDF" => 2734
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S0873215913000950"
    "issn" => "08732159"
    "doi" => "10.1016/j.rppneu.2013.06.006"
    "estado" => "S300"
    "fechaPublicacion" => "2013-11-01"
    "aid" => "172"
    "copyright" => "Sociedade Portuguesa de Pneumologia"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "sco"
    "cita" => "Rev Port Pneumol. 2013;19:276-80"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 7001
      "formatos" => array:3 [
        "EPUB" => 239
        "HTML" => 5552
        "PDF" => 1210
      ]
    ]
    "pt" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Publica&#231;&#227;o breve</span>"
      "titulo" => "Aplica&#231;&#227;o t&#243;pica de mitomicina-<span class="elsevierStyleSmallCaps">C</span> como adjuvante no tratamento broncosc&#243;pico da estenose traqueal p&#243;s-entuba&#231;&#227;o"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => array:2 [
        0 => "pt"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "276"
          "paginaFinal" => "280"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Topical application of mitomycin-C as an adjuvant treatment to bronchoscopic procedures in post-intubation tracheal stenosis"
        ]
      ]
      "contieneResumen" => array:2 [
        "pt" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1017
              "Ancho" => 1660
              "Tamanyo" => 144536
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Resultados do tratamento com BR&#47;MMC apresentados por percentagem de estenose do l&#250;men traqueal&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "F&#46; Viveiros, J&#46; Gomes, A&#46; Oliveira, S&#46; Neves, J&#46; Almeida, J&#46; Moura e S&#225;"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "Viveiros"
            ]
            1 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Gomes"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Oliveira"
            ]
            3 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Neves"
            ]
            4 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Almeida"
            ]
            5 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Moura e S&#225;"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S2173511513000705"
        "doi" => "10.1016/j.rppnen.2013.10.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511513000705?idApp=UINPBA00004E"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215913000950?idApp=UINPBA00004E"
    "url" => "/08732159/0000001900000006/v2_201509041406/S0873215913000950/v2_201509041406/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0873215913000846"
    "issn" => "08732159"
    "doi" => "10.1016/j.rppneu.2013.03.007"
    "estado" => "S300"
    "fechaPublicacion" => "2013-11-01"
    "aid" => "169"
    "copyright" => "Sociedade Portuguesa de Pneumologia"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Rev Port Pneumol. 2013;19:260-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 6419
      "formatos" => array:3 [
        "EPUB" => 264
        "HTML" => 4929
        "PDF" => 1226
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Is <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT prognostic factor for survival in patients with small cell lung cancer&#63; Single center experience"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "260"
          "paginaFinal" => "265"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "&#201; o <span class="elsevierStyleSup">18</span>F -FDG-PET&#47;CT um fator de progn&#243;stico para a sobreviv&#234;ncia em pacientes com cancro pulmonar de pequenas c&#233;lulas&#63; Experi&#234;ncia num &#250;nico centro"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1453
              "Ancho" => 1394
              "Tamanyo" => 90137
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Survival of patients according to performance status&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "A&#46; Inal, M&#46; Kucukoner, M&#46;A&#46; Kaplan, Z&#46; Urakc&#305;, N&#46; Nas, M&#46; Guven, Z&#46; Dostbil, S&#46; Alt&#305;ndag, A&#46; Is&#305;kdogan"
          "autores" => array:9 [
            0 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Inal"
            ]
            1 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Kucukoner"
            ]
            2 => array:2 [
              "nombre" => "M&#46;A&#46;"
              "apellidos" => "Kaplan"
            ]
            3 => array:2 [
              "nombre" => "Z&#46;"
              "apellidos" => "Urakc&#305;"
            ]
            4 => array:2 [
              "nombre" => "N&#46;"
              "apellidos" => "Nas"
            ]
            5 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Guven"
            ]
            6 => array:2 [
              "nombre" => "Z&#46;"
              "apellidos" => "Dostbil"
            ]
            7 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Alt&#305;ndag"
            ]
            8 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Is&#305;kdogan"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215913000846?idApp=UINPBA00004E"
    "url" => "/08732159/0000001900000006/v2_201509041406/S0873215913000846/v2_201509041406/en/main.assets"
  ]
  "en" => array:18 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "New advances in the therapy of non-cystic fibrosis bronchiectasis"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "266"
        "paginaFinal" => "275"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "A&#46; Amorim, F&#46; Gamboa, P&#46; Azevedo"
        "autores" => array:3 [
          0 => array:4 [
            "nombre" => "A&#46;"
            "apellidos" => "Amorim"
            "email" => array:1 [
              0 => "adelinamorim&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "Gamboa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "P&#46;"
            "apellidos" => "Azevedo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Pneumology Department&#44; Centro Hospitalar S&#227;o Jo&#227;o&#44; EPE&#44; Faculty of Medicine&#44; University of Porto&#44; Porto&#44; Portugal"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Pneumology Department&#44; Centro Hospitalar e Universit&#225;rio de Coimbra-Hospitais da Universidade de Coimbra&#44; EPE&#44; Coimbra&#44; Portugal"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Pneumology Department&#44; Centro Hospitalar Santa Maria&#44; Faculty of Medicine&#44; University of Lisbon&#44; Lisbon&#44; Portugal"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "pt" => array:1 [
        "titulo" => "Novos avan&#231;os no tratamento da Bronquiectasia n&#227;o-fibrose c&#237;stica"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bronchiectasis &#40;BE&#41; is an abnormal and irreversible dilation of the bronchi&#44; which has numerous causes&#46; Its frequency depends on the patient&#39;s age and sex&#44; social and economic conditions and the degree of applied investigation&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">There was little interest in the investigation of non-cystic fibrosis BE&#44; this includes therapeutic approaches&#44; in the last few decades&#44; probably due to supposedly low prevalence and the assumption that treatment is the same for all patients and that little can be done to change the symptoms and evolution&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The publication of diagnosis and treatment reviews in the last few years<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> demonstrates a growing interest in this pathology&#46; The level of evidence for most recommendations however is low&#44; because of the absence of large double-blind&#44; placebo-controlled trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The existence of strong evidence supporting the use of some drugs in patients with cystic fibrosis &#40;CF&#41; does not mean that they will be good for patients with BE of another etiology&#46; So&#44; it is not correct to extrapolate the CF trial results to the non-CF patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In CF&#44; the forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s &#40;FEV1&#41; is one of the most important trial end-points&#46; In non-CF BE it has been difficult to establish appropriate end-points to evaluate the effect of new therapeutic interventions&#46; To date it seems that improvement in quality of life is one of the most important outcome measures&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">BE is characterized by a vicious cycle of infection&#44; inflammation and further sputum production&#46; In this review we decided to focus on three important pharmacological groups that aim to interfere with each part of the cycle and in which there have been relevant advances&#46; Nevertheless&#44; BE treatment should be embraced and specific therapies for the underlying cause as well as interventions like physiotherapy&#44; pulmonary rehabilitation&#44; nutritional support and&#44; in selected patients&#44; surgical intervention need to be kept in mind&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Mucoactive therapy</span><p id="par0035" class="elsevierStylePara elsevierViewall">Regardless of the cause&#44; BE is mainly characterized by bronchial infection and persistent inflammation which could be the cause and consequence of impaired airway mucous clearance&#46; The mucus progressively becomes viscous due to the presence of inflammatory cells&#44; microorganisms and large polymers and turns into sputum&#44; overwhelming the ciliary clearance capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The mucus clearance requires a balance between periciliary liquid volume&#44; mucus composition and volume and normal ciliary beat frequency&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> One of these steps could be more particularly affected depending on the cause of BE&#59; the therapeutic intervention should ideally be focused on the main mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Unfortunately in many cases this is not clear and there is probably a mix of mechanisms involved so the development of combined therapies would be more appropriate&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The pathogenesis process mostly accepted in CF indicates a relative dehydration and a reduction in airway surface liquid volume&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Therefore airway hydration is an important goal in the overall therapeutic management of this disease&#46; However&#44; it is generally accepted that even in the absence of dehydration the increase in water improves mucus clearance by decreasing surface interactions&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In this context the most recent advances in the treatment of mucociliary dysfunction are targeted at increasing hydration on airway surface by inhaled hyperosmolar agents&#44; like mannitol and hypertonic saline &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Both the agents increase the osmolarity of the airway surface fluid causing influx of water into the airway and reducing the viscoelastic properties of the mucus by breaking some of the mucin bonds&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">As inhalation of hyperosmolar agents may induce airway narrowing and a reduction in FEV1 of about 15&#37; in sensitive subjects&#44; an assessment of bronchial hyperresponsiveness is recommended before starting treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Mannitol</span><p id="par0055" class="elsevierStylePara elsevierViewall">Mannitol is a nonionic sugar alcohol&#44; commonly used as an osmotic agent&#44; which increases mucus clearance&#46; The precise mechanism of this action is unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Studies have demonstrated that the effect of mannitol is acute rather than cumulative but it has a sustained effect for up to 24<span class="elsevierStyleHsp" style=""></span>h&#46; The mucociliary clearance effect was also found in all regions of the lung&#44; including the peripheral region&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Mannitol capsules &#40;40<span class="elsevierStyleHsp" style=""></span>mg&#41; which contain dry powder for inhalation using an inhaler device are commercially available&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> They have been approved for the treatment of CF in adults aged &#8805;18 years&#46; The recommended dose is 400<span class="elsevierStyleHsp" style=""></span>mg &#40;which requires the inhalation of the content of 10 capsules loaded individually into the inhaler&#41; twice a day&#44; once in the morning and once in the evening&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Mannitol has the advantage of being a powder formulation and therefore has a shorter delivery time which avoids the usual maintenance and cleaning issues related with nebulizer devices&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">An international phase-III randomized double-blind placebo-controlled trial of inhaled dry powder mannitol &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#41; was carried out on 324 CF patients&#44; for a 26-week period&#44; twice daily&#46; This showed a significant improvement in FEV1 &#40;change from baseline 118<span class="elsevierStyleHsp" style=""></span>mL &#40;6&#46;5&#37;&#41; <span class="elsevierStyleItalic">versus</span> 26<span class="elsevierStyleHsp" style=""></span>mL &#40;2&#46;4&#37;&#41;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Improvements in FEV1 were seen fairly early &#40;at 6 weeks&#41; and were maintained up to 52 weeks&#46; There was also a 35&#46;4&#37; reduction in the incidence of exacerbation on the mannitol group&#46; It is worth noting that the lung function improvement was found irrespective of the concomitant use of recombinant human deoxyribonuclease &#40;rhDNase&#41;&#46; Cough and haemoptysis were the most common adverse events&#46; Overall they were mild or moderate and only a small proportion of patients had to discontinue the treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Given these results&#44; mannitol was also tested on non-CF BE and even though the first studies were carried out on small groups of patients&#44; during short periods of time and mostly relating to non-clinical issues&#44; they showed promising results of its use in this patient population&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">An open-label study of mannitol &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; carried out on 9 patients with BE&#44; once daily&#44; during a 12-day period documented a highly significant improvement in quality of life&#44; which is assessed by St George&#39;s Respiratory Questionnaire &#40;SGRQ&#41;&#44; and maintained for 6&#8211;10 days after cessation of treatment&#46; It is important to note that patients reported a reduction in cough during both day and night&#44; a reduction of sputum in the morning and an increase in sleeping time&#46; Some properties of sputum were changed&#44; increasing cough efficacy&#46; No significant changes in lung function were found&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A phase-3 multicentre randomized controlled trial&#44; available only in abstract&#44; involving 185 BE patients with mild-to-moderate lung function demonstrated an improvement in health-related quality of life with inhaled mannitol &#40;320<span class="elsevierStyleHsp" style=""></span>mg&#41; over 12 weeks&#46; Furthermore a prolonged time free of antibiotics and a lower total use of antibiotics compared with placebo was observed&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">A phase-III clinical trial is in progress and the purpose of this study is to examine the efficacy and safety of a 52-week treatment with 400<span class="elsevierStyleHsp" style=""></span>mg inhaled mannitol&#44; twice daily&#44; against a control group&#46; The primary outcome measure is the effect of mannitol in reducing the pulmonary exacerbations and the secondary outcomes are the difference in quality of life&#44; antibiotic use&#44; number of hospitalizations&#44; sputum volume&#44; daytime sleepiness scores&#44; lung function and health related costs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Hypertonic saline solution</span><p id="par0085" class="elsevierStylePara elsevierViewall">Hypertonic saline &#40;HS&#41; is an ionic substance quickly transported across the epithelium and delivered using an ultrasonic or jet nebulizer&#46; The highest well tolerated concentration is 7&#37;&#46; Its utility was well documented for CF in a randomized placebo-controlled trial in 164 patients&#44; twice daily&#44; over 48 weeks&#46; The HS group had significantly fewer pulmonary exacerbations&#44; an improvement in quality of life&#44; a reduction in absenteeism from school and work and an improvement in FEV1 of 65<span class="elsevierStyleHsp" style=""></span>ml&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> A Cochrane review in 2009&#44; including 12 trials&#44; concluded that HS is a safe&#44; low-cost and effective therapy in CF&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>However&#44; the HS recommendation for non-CF BE is not clear&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In a crossover trial 24 BE patients&#44; who produced less than 10<span class="elsevierStyleHsp" style=""></span>g of sputum per day&#44; were randomly selected to receive four single treatment schedules once a week&#44; for 4 weeks&#46; This included active cycle breathing technique &#40;ACBT&#41; alone&#59; nebulized terbutaline followed by ACBT after 10<span class="elsevierStyleHsp" style=""></span>min&#59; nebulized terbutaline followed after 10<span class="elsevierStyleHsp" style=""></span>min by nebulized isotonic saline &#40;IS&#41; &#40;09&#37;&#41; then ACBT&#59; nebulized terbutaline followed after 10<span class="elsevierStyleHsp" style=""></span>min by nebulized HS &#40;7&#37;&#41; then ACBT&#46; Both nebulized IS and HS were significantly more effective in increasing sputum yield&#44; reducing sputum viscosity and improving ease of expectoration but HS was significantly better than IS&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In another randomized single blind crossover trial to evaluate IS and HS daily for 3 months in 28 BE patients&#44; a significant improvement in lung function &#40;FEV1 and FVC&#41; and quality of life was documented by changes in global scores and subscales of symptoms and impact of SGRQ in favor of HS&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A recently published research showed different results&#46; Forty patients were randomized to inhale IS or HS 6&#37; daily for 12 months and no important clinical superiority of HS over IS was identified&#46; Nevertheless&#44; there were significant improvements in quality of life&#44; lung function and sputum colonization in both groups&#46; Noteworthy is that prior to the trial 85&#37; of the patients regularly performed airway clearance techniques&#44; which means that the daily use of a saline solution may offer additional benefits&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Even though there is some evidence favoring HS&#44; it seems that both hypertonic and isotonic saline are beneficial in non-CF BE&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21&#44;21</span></a> These results agree with another randomized placebo-controlled study that evaluated the clinical utility of long-term humidification therapy in 108 patients with COPD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#41; or BE &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#46; They used fully humidified high flow air at 37<span class="elsevierStyleHsp" style=""></span>&#176;C through nasal cannulae&#44; daily&#44; over a 12-month period&#46; The patients on long-term humidification therapy showed significantly fewer exacerbation days&#44; increased time to first exacerbation&#44; improvement in quality of life and lung function&#46; There was a non-significant reduction in exacerbation frequency&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">N-acetylcysteine</span><p id="par0110" class="elsevierStylePara elsevierViewall">N-acetylcysteine &#40;NAC&#41; is commonly used in the treatment of BE patients&#46; It is a mucolytic agent that disrupts the disulfide bonds in mucus when inhaled&#46; After oral administration there is no NAC in airway secretions but cysteine is detected in the plasma and induces an increase in glutathione levels in the plasma and lung which has antioxidant properties&#46; Therefore the benefits of this agent may come from its antioxidant properties and not its mucolytic characteristics&#46; NAC has also antibacterial properties by reducing the ability of bacteria to adhere to epithelial cells&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Despite this&#44; in 2001 a Cochrane review concluded that there is no evidence to recommend the use of NAC in non-CF BE&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Sputum clearance is a complex mechanism&#44; with several targets&#44; which is not completely understood&#46; Trials of mucoactive agents are scarce and there are some discordant results&#46; The latter may be explained by the fact that the analyses are usually independent of the underlying disease&#46; With sub-group analyses&#44; clear benefits would probably be discovered&#44; which underlines the importance of defining the etiology&#46; An example of this is the bad results obtained with rhDNase in non-cystic fibrosis BE&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> as it not only failed to improve FEV1 but also the patients got worse&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Anti-inflammatory therapy</span><p id="par0120" class="elsevierStylePara elsevierViewall">As stated before&#44; persistent inflammation is a cardinal feature of BE<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#59; it is part of a vicious cycle which also involves host susceptibility&#44; sputum hypersecretion&#44; airway obstruction and infection&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Sometimes&#44; even in the absence of existing infection there is continuous neutrophilic infiltration of the airways which suggests dysregulation of immune responses&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In this setting&#44; it is reasonable to consider anti-inflammatory and&#47;or immunomodulatory therapies as an option in the management of patients with BE&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Although it is a disease which is increasingly recognized and studied&#44; evidence to support the use of anti-inflammatory therapies is still limited even when taking into account drugs with an established anti-inflammatory role in the treatment of other disorders&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Macrolides</span><p id="par0130" class="elsevierStylePara elsevierViewall">Apart from their antimicrobial activity&#44; macrolides have been increasingly used in clinical practice for the treatment of a variety of chronic pulmonary diseases because of their anti-inflammatory and immune-modulatory properties&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;32</span></a> Although solid evidence to justify long-term macrolide therapy in many of these disorders is still lacking&#44; beneficial effects have been found in small clinical trials of patients with non-CF BE&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#8211;39</span></a> There were considerable variations in the study design of many of these trials&#44; including duration&#44; dose and macrolides tested and outcome measures evaluated but most of them showed consistent evidence of a decrease in sputum volume and some reported a decrease in exacerbation frequency&#46; Several larger studies which have recently been completed corroborate these findings&#46; A significant reduction in exacerbation frequency was found in the preliminary results of a trial with 89 patients which compared the use of azithromycin with a placebo<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> as well as in another study yet to be published with 117 patients using erythromycin&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Accordingly&#44; the largest study to date&#44; which has recently been published&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> demonstrated that a 6 months azithromycin treatment significantly decreased the rate of exacerbations requiring antibiotic therapy&#44; which was sustained for 6 months after completion of treatment&#44; and increased the time to the first exacerbation requiring antibiotics&#46; As well as these beneficial effects&#44; however&#44; it is important to realize that side effects such as gastrointestinal upset&#44; raised transaminase levels&#44; cardiac arrhythmias &#40;particularly prolonged QT interval related&#41;&#44; auditory impairment&#44; urogenital candidiasis and&#44; lastly&#44; and possibly most importantly&#44; the risk of microbial macrolide resistance&#44; particularly non-tuberculous mycobacteria &#40;NMT&#41;&#44; may occur&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;43</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Therefore&#44; macrolides cannot be recommended as routine therapy for non-CF BE before further research is carried out&#44; although their use&#44; particularly azithromycin&#44; can be considered in selected patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;44</span></a> In patients with frequent respiratory exacerbations or continuous symptoms for more than 6 months&#44; particularly if chronically infected with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44; a trial of 3&#8211;6 months of 3 times per week 250&#8211;500<span class="elsevierStyleHsp" style=""></span>mg azithromycin can be done after ruling out NTM infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;44</span></a> Transaminase monitoring should be performed in the first few weeks of treatment and then&#44; as well as NTM screening&#44; every 6 months if there is evidence of benefit to the patient in terms of quality of life and frequency of exacerbations and the therapy is not discontinued&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There are no studies to support either the effectiveness or safety of treatments of more than 12 months duration&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">An overview of the available studies showing the effects of macrolides in patients with BE is presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Corticosteroids</span><p id="par0145" class="elsevierStylePara elsevierViewall">Despite their potent anti-inflammatory action&#44; long-term systemic corticosteroids cannot be used due to potential adverse effects&#46; Inhaled corticosteroids&#44; however&#44; have been studied in patients with BE and a 2009 review by Kapur et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> identified six randomized clinical trials which enrolled 278 of 303 randomized adult patients&#46; This meta-analysis concluded that there was insufficient evidence to recommend the routine use of inhaled steroids in adults with stable state BE but considered that a therapeutic trial might be justified in patients with difficult to control symptoms&#59; these would have to be closely monitored for adverse events especially if high doses were used&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">A recently published Spanish study<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> reported the potentially beneficial effect of the addition of a long acting beta-2 adrenergic to inhaled corticosteroid on clinical parameters and health-related quality of life by allowing the dose of the inhaled steroid to be reduced to half with a reduction of local side effects&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">These findings need to be assessed with larger controlled randomized trials&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Other anti-inflammatory agents</span><p id="par0160" class="elsevierStylePara elsevierViewall">Non-steroidal anti-inflammatory drugs &#40;NSAID&#41; may also be a potentially attractive therapy in patients with BE as ibuprofen has demonstrated beneficial effects on people with CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a> However&#44; two Cochrane Database systemic reviews searching for use of oral<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> and inhaled NSAID<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> in non-CF BE only identified one single trial of inhaled indomethacin <span class="elsevierStyleItalic">versus</span> placebo in 24 adults&#44; 8 of them with BE&#46; This study documented a significant reduction in sputum production and dyspnea in the treatment group over 14 days but further studies on the efficacy of NSAIDs in treating patients with BE are needed&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Like macrolides&#44; another class of drugs that have recognized anti-inflammatory and immunomodulatory properties are hydroxy-methyl-glutaryl-conzymeA reductase inhibitors &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span> statins&#41; which have demonstrated <span class="elsevierStyleItalic">in vitro</span> inhibition of neutrophil migration and epithelial cell production of chemoattractants and proteases and potentiation of macrophage efferocytosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51&#44;52</span></a> As efferocytosis appears to be involved in the pathogenesis of a variety of chronic lung and systemic inflammatory disease including BE&#44; this would seem an attractive target for statins therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> There are currently ongoing clinical trials to evaluate the effect of atorvastatin on patients with BE&#44; with and without <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">54&#44;55</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Leukotriene receptor antagonists may theoretically be of benefit as they inhibit neutrophilic mediated inflammation but there are no controlled studies to date to support their use in BE&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Methylxanthines are also theoretically of use in BE as they are purported to have anti-inflammatory properties but&#44; although there are no published studies to date&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> there are trials currently underway to assess the effect of theophylline in the treatment of bronchiectasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">58&#44;59</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Agents specifically targeting a particular mediator of the immune response might be an interesting new class of drugs in the future&#46; Roflumilast and specific monoclonal antibodies&#44; <span class="elsevierStyleItalic">e&#46;g&#46;</span> against IL-8&#44; matrix metalloproteases &#40;MMPs&#41; or neutrophil elastase&#44; are in this group but the safety and tolerability of these drugs still need to be assessed in phase II and III studies&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Antibiotic therapy</span><p id="par0185" class="elsevierStylePara elsevierViewall">BE provides the perfect environment for colonization by various microorganisms&#44; as mucociliary clearance is impaired&#44; facilitating rapid bacterial growth on the airways mucosal surface without tissue invasion&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In spite of the fact that these bacteria do not cause invasive disease and are usually less virulent than those that invade nearby tissues&#44; they are able to trigger an inflammatory response that aims to eliminate the microorganism&#59; when this purpose fails&#44; however&#44; the inflammation becomes chronic and leads to progressive severe lung injury&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">These pathogens can also develop the means to facilitate their own survival&#44; overcoming host defence mechanisms and antimicrobial actions through biofilm production and other bacterial resistance mechanisms&#46; Thus&#44; the chronic colonization process that occurs in the respiratory tract of patients with BE is called &#8220;pathogenic colonization&#8221;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> and can be divided into three different phases&#58; <span class="elsevierStyleItalic">initial colonization</span> &#40;the first isolate of a microorganism&#41;&#44; <span class="elsevierStyleItalic">intermittent colonization</span> &#40;intermittent isolation of the same microorganism in cultures separated by&#44; at least&#44; a month&#44; representing a chronic colonization process with a low bacterial load&#41; and <span class="elsevierStyleItalic">chronic colonization</span> &#40;three or more successive positive cultures for the same microorganism with&#44; at least&#44; one month apart&#44; within a period of six months&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Exacerbation is a clinical situation that can happen during any of the three scenarios mentioned above&#44; and it has the potential to worsen lung function deterioration&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> The diagnosis of exacerbation in these patients is particularly difficult and is based on the acute development of manifestations such as changes in sputum characteristics &#40;increased volume&#44; purulence and viscosity&#41;&#44; haemoptysis&#44; breathlessness&#44; worsening of cough&#44; chest pain&#44; fever&#44; asthenia&#44; anorexia&#44; weight loss&#44; physical changes in thoracic examination&#44; desaturation&#44; decline in lung function&#44; radiologic signs of lower respiratory tract infection and elevation of systemic biomarkers of inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Several microorganisms can be isolated from the respiratory tract of patients with non-CF BE and the acquisition and clearance of a strain is a complex&#44; dynamic process involving host factors and receptor sites on the organism that may help define its ability to persist and damage airways&#46; There is a slight difference in the dynamics of colonization according to age&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The most frequently isolated pathogens are <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44; <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and <span class="elsevierStyleItalic">Streptococcus pneumonia&#46;</span><a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">61&#44;62</span></a> In children the predominant isolated pathogen is <span class="elsevierStyleItalic">H&#46; influenzae</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#8211;65</span></a> whereas in adults&#44; although <span class="elsevierStyleItalic">H&#46; influenzae</span> is still the most frequently isolated pathogen&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;28&#44;61</span></a> there is a significantly higher isolation rate of <span class="elsevierStyleItalic">P&#46; aeruginosa&#46;</span><a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a><span class="elsevierStyleItalic">S&#46; pneumoniae</span> and <span class="elsevierStyleItalic">Moraxella catharralis</span> are also found in a significant but variable rate and <span class="elsevierStyleItalic">Aspergillus fumigatus</span> is rarely isolated&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> Isolation of <span class="elsevierStyleItalic">Staphylococcus aureus</span> should lead to consideration of underlying CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;26&#44;66</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">P&#46; aeruginosa</span> has a propensity to persist in bronchiectatic airways due to its capacity to produce virulence factors and modulate immune defences by quorum signaling and biofilm production&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Since infection &#40;and particularly <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection&#41; plays a major role in causing and perpetuating BE&#44; reducing the microbial load using antibiotics is a cornerstone of therapy&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> either through treating exacerbations or by using suppressive antibiotic strategies&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">However&#44; the isolation of one or more pathogens in the sputum of patients with non-CF BE is not necessarily an indication for antibiotic treatment&#44; particularly in adults<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a>&#59; there are three main criteria for prescribing antibiotics in this setting&#58; exacerbation&#44; eradication of the first isolate of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and suppressive therapy in steady-state BE chronically colonized with <span class="elsevierStyleItalic">P&#46; aeruginosa&#46;</span></p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Treatment of exacerbations</span><p id="par0230" class="elsevierStylePara elsevierViewall">Early treatment of exacerbations is particularly important as it could probably limit the vicious circle of infection&#47;inflammation that is a determinant factor of lung damage&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The management of these patients includes routine cultures of respiratory secretions to identify infecting organisms and guide antibiotic selection as these patients frequently carry the same bacteria for prolonged periods of time&#46; The current recommendation is to perform cultures every three months on average&#44; so that updated information is available to guide treatment when a pulmonary exacerbation occurs&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Without this information the choice of antibiotic has to be empirical&#44; based on the most common organisms associated with exacerbations in these patients&#44; in particular <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46; Nevertheless&#44; before starting antibiotic therapy&#44; a sputum sample should be sent off for culture&#44; after which antibiotics should be started and then eventually changed in accordance with the microorganism isolated and its antibiogram&#46; However&#44; <span class="elsevierStyleItalic">in vitro</span> antibiotic sensitivity does not always correlate with therapeutic response&#44; which happens with microorganisms able to form a biofilm&#44; where the activity of many antibiotics is diminished&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> So&#44; although an antibiogram is essential for guiding treatment&#44; the value of conventional <span class="elsevierStyleItalic">in vitro</span> susceptibility testing for these patients is being questioned&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">It is also common to isolate more than one microrganism or distinct morphotypes of the same pathogen with the same or different patterns of antimicrobial sensitivity&#46; Selecting an antibiotic combination that covers all the isolates can be difficult without resorting to an impractically large number of antibiotics&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The route of administration will depend on the severity of the exacerbation and the evidence of colonization by multidrug resistant microorganisms&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Mild exacerbations can be treated orally with a fluoroquinolone on an outpatient basis&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">70&#44;71</span></a> The addition of inhaled tobramycin solution &#40;TS&#41; to ciprofloxacin was studied because of concerns regarding virulence and potential resistance of <span class="elsevierStyleItalic">Pseudomonas</span>&#46; In a double-blind&#44; multicenter trial&#44; 53 patients with non-CF BE and respiratory exacerbations due to <span class="elsevierStyleItalic">Pseudomonas</span> were randomly assigned to receive ciprofloxacin plus TS or plus placebo for two weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> The addition of TS did not improve clinical outcomes although there was a marked reduction of <span class="elsevierStyleItalic">Pseudomonas</span> density in the sputum&#46; Based on this&#44; TS cannot be recommended alone or in combination with ciprofloxacin for acute exacerbations in non-CF BE&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Intravenous therapy is reserved for oral therapy failure&#44; severe exacerbations or microorganisms resistant to oral antibiotics&#46; The most commonly selected intravenous regimen combines two antibiotics &#40;usually a &#946;-lactam anti-<span class="elsevierStyleItalic">Pseudomonas</span>&#58; piperacillin-tazobactam&#44; ceftazidime or meropenem&#41; and an aminoglycoside&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#44;70</span></a> The rationale for choosing two rather than one is based on the possibility of obtaining synergic effects and decreasing the risk of antibiotic resistances&#46; Regarding the aminoglycoside&#44; tobramycin is recommended due to its strong activity against <span class="elsevierStyleItalic">P&#46; aeruginosa</span> compared to other aminoglycosides&#46; In cases of tobramycin resistance&#44; amikacin can be used&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Adding an inhaled antibiotic to an intravenous one has not been shown to provide clinical benefits&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">There is no evidence to recommend combination antibiotics in patients colonized with microorganisms other than <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; unless there is more than one pathogen&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Exacerbations should be treated using a high dosage targeted antibiotic therapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> due to the fact that the volume of distribution and total body clearance for hydrophilic drugs &#40;such as aminoglycosides&#44; penicillins&#44; and cephalosporins&#41; are increased because these patients are generally undernourished and have decreased adipose tissue&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">The duration of antibiotic therapy is also a matter of debate requiring further investigation but the expert consensus is that 14 days should be recommended for all exacerbations&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4&#44;60&#44;69</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infection&#47;colonization</span><p id="par0280" class="elsevierStylePara elsevierViewall">As the disease progresses chronic infection by <span class="elsevierStyleItalic">P&#46; aeruginosa</span> becomes common and it seems to be an independent risk factor for accelerated loss of pulmonary function and decreased survival&#46; Conversion of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> to the mucoid phenotype worsens prognosis although it is more common in patients with CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">74&#44;75</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Although there are no studies to guide practice following the <span class="elsevierStyleItalic">first isolation</span>&#44; an attempt to eradicate seems pragmatic for what it should be treated aggressively regardless of the patient&#39;s clinical signs or symptoms in order to eliminate the microorganism from the sputum as it is very difficult to do so once chronic colonization is established&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">In non-CF BE the strategy proposed for eradication is oral ciprofloxacin for 3 weeks and if it fails&#44; the same protocol as for CF is recommended &#40;nebulized antibiotic&#58; tobramycin&#44; sodium colistimethate or aztreonam lysine&#41; plus oral ciprofloxacin for 3 weeks&#44; followed by inhaled antibiotics for 3&#8211;12 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;60&#44;76</span></a> An alternative would be an association of 2 anti-<span class="elsevierStyleItalic">Pseudomonas</span> intravenous antibiotics for 14&#8211;21 days&#44; followed by an inhaled antibiotic for 3&#8211;12 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;60&#44;76</span></a> As was stated above&#44; an antibiogram is essential for guiding treatment although it is recognized that <span class="elsevierStyleItalic">in vitro</span> sensitivity does not always correlate with therapeutic response&#46; However&#44; for nebulized antibiotics the interpretation of the antibiogram should take into consideration that&#44; through this form of delivery&#44; antibiotic achieves much higher concentrations in the bronchial mucosa overcoming the mechanisms of resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">The persistence of bacteria despite aggressive treatment is thought to be due to several factors such as poor penetration of antibiotics into purulent airway secretions&#44; native or acquired antibiotic resistance and production of biofilms by the bacteria that may render antibiotics ineffective or interfere with host defences&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">To prevent the decline in lung function associated to chronic bronchial colonization with this pathogen&#44; nebulized antibiotics that show <span class="elsevierStyleItalic">in vitro</span> activity against <span class="elsevierStyleItalic">P&#46; aeruginosa</span> are frequently used as chronic suppressive therapy&#46; The aim of this strategy is to reduce the bacterial burden &#40;as in this phase it is virtually impossible to eradicate the pathogen&#41; and&#44; thus&#44; reduce the inflammatory response that leads to structural lung damage and loss of function&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;78</span></a> avoiding the cumbersome and toxic iatrogenic effects associated to oral or intravenous route&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a> It seems that this strategy may reduce the frequency and severity of respiratory exacerbations and the decline in lung function&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">80&#44;81</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">One trial conducted in 2000 randomly assigned 74 patients with non-CF BE and <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection to receive aerosolized tobramycin &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#44; twice daily&#41; or aerosolized placebo for 28 days&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> Patients in the treatment group demonstrated a 10&#44;000-fold reduction in <span class="elsevierStyleItalic">Pseudomonas</span> density&#44; but no change in FEV1 as compared to controls&#46; The same results were attained in a similar trial conducted in 2001&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">In 2005&#44; a 6 month double blind crossover study of aerosol tobramycin was carried out on 30 patients and revealed no change in exacerbation rate&#44; but the number of hospitalizations and duration of hospital stay were reduced during the tobramycin phase&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">In 2005 a smaller uncontrolled study was carried out in which aerosolized tobramycin &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#44; twice daily&#41; was administered to 41 patients with non-CF BE and <span class="elsevierStyleItalic">Pseudomonas</span> infection&#59; the protocol alternated two weeks with therapy and two weeks without&#44; for a total of 12 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a> Treatment was associated with a decrease in symptoms and improvements in health-related quality of life &#40;QOL&#41;&#46; However&#44; 10 of 41 patients were unable to complete the protocol because of side effects &#40;cough&#44; wheezing or worsened dyspnea&#41;&#44; and two of the patients who completed the trial acquired tobramycin-resistant <span class="elsevierStyleItalic">Pseudomonas</span> species&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">In 2007 an uncontrolled study examined the efficacy of nebulized colistin in a mixed population of patients with COPD and bronchiectasis colonized with PSAE and showed an improvement in quality of life and slower decline with FEV1 with treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">Currently&#44; many other clinical trials are being carried out with the purpose of establishing the indications for inhaled antibiotic therapy in these patients and define which antibiotics to use and the most appropriate devices to deliver them&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">In fact&#44; at the moment&#44; the clinical evidence that supports the use of chronic inhaled antibiotherapy in non-CF BE&#44; chronically colonized with <span class="elsevierStyleItalic">Pseudomonas</span>&#44; is scarce but all the data suggest that this therapeutic strategy seems to control the symptoms&#44; prevent the progression of the disease and reduce the morbidity with no relevant adverse events&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">87&#44;88</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">The chronic antibiotherapy may be intermittent &#40;28 days <span class="elsevierStyleItalic">on</span>&#44; 28 days <span class="elsevierStyleItalic">off</span>&#41; when using tobramycin or aztreonam lysine or continuous when using sodium colistimethate&#46; However&#44; continuous inhaled antibiotherapy should be prescribed using 2 different antibiotics alternately in patients that are very symptomatic in <span class="elsevierStyleItalic">off</span>-periods&#44; or with severe lung function impairment or recurrent pulmonary exacerbations despite taking one antibiotic every other month&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">Nevertheless&#44; there is still a degree of uncertainty about when to prescribe the various inhaled antibiotics and what to choose&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">At the moment the recommendations<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> are to treat patients with non-CF BE chronically colonized with <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and with frequent acute exacerbations &#40;three or more per year&#41; or progressive deterioration of lung function&#44; with inhaled antibiotics&#59; it seems reasonable to use tobramycin as the first choice because of the extensive information supporting its efficacy and good safety record after many years of use&#46; The level of evidence and clinical benefit is greatest for patients with moderate or severe lung disease&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">The option for inhaled aztreonam instead of tobramycin may be considered if there is evidence of inhaled tobramycin intolerance&#44; clinical deterioration despite inhaled tobramycin&#44; a strong possibility of increasing adherence due to the fact that inhaled aztreonam can be delivered more rapidly than tobramycin and evidence or possibility of pregnancy when aminoglycosides are relatively contraindicated&#46; Data are needed from well-designed comparative effectiveness trials for tobramycin and aztreonam to provide for a more informed decision as to which to use&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Given the less than robust data supporting its use and the suggestion that it may be inferior&#44; it seems reasonable to prescribe colistin only in cases of tobramycin therapeutic failure or intolerance&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">In conclusion&#44; controlling respiratory infection&#47;colonization is the cornerstone of therapy in non-CF BE with a significant impact on survival for which more robust data are needed to support decisions in this area&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion</span><p id="par0365" class="elsevierStylePara elsevierViewall">BE has recently became a hot topic&#46; First results of well designed trials have been published and several studies are in progress&#46; However&#44; there are many questions regarding treatment which are still waiting for scientific answers&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">It will be important to design studies involving a greater number of patients&#44; with different levels of severity&#44; more specific aetiological information and carried out over longer time periods to clarify the real benefits of these promising therapies and bring new insights into this interesting topic&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical disclosures</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of human and animal subjects</span><p id="par0375" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Confidentiality of data</span><p id="par0380" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0385" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0390" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres547681"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec565561"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres547680"
          "titulo" => "Resumo"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec565560"
          "titulo" => "Palavras-chave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Mucoactive therapy"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Mannitol"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Hypertonic saline solution"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "N-acetylcysteine"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Anti-inflammatory therapy"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Macrolides"
            ]
            1 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Corticosteroids"
            ]
            2 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Other anti-inflammatory agents"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0050"
          "titulo" => "Antibiotic therapy"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Treatment of exacerbations"
            ]
            1 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Treatment of Pseudomonas aeruginosa infection&#47;colonization"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclusion"
        ]
        9 => array:3 [
          "identificador" => "sec0070"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflicts of interest"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-03-17"
    "fechaAceptado" => "2013-03-21"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec565561"
          "palabras" => array:6 [
            0 => "Non-cystic fibrosis bronchiectasis"
            1 => "Advances"
            2 => "Mucoactive"
            3 => "Anti-inflammatory"
            4 => "Antibiotic"
            5 => "Therapy"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec565560"
          "palabras" => array:6 [
            0 => "Bronquiectasia n&#227;o-fibrose c&#237;stica"
            1 => "Avan&#231;os"
            2 => "Mucoactivo"
            3 => "Anti-inflamat&#243;rio"
            4 => "Antibi&#243;tico"
            5 => "Terapia"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Non-cystic fibrosis bronchiectasis remains a common and important respiratory disease to date&#46; It is a chronic pathology and consequently the patients usually require continuous treatment&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In recent decades therapies that do not have scientific evidence of their benefits have been commonly used in non-cystic fibrosis bronchiectasis&#46; Cystic fibrosis has provided the experience to extrapolate therapeutic approaches to other bronchiectasis patients&#46; Finally&#44; in the last few years some trials have been carried out specifically in non-cystic fibrosis bronchiectasis which aim to assess the efficacy of some of the treatments which are commonly used but sometimes without clear indication&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This review will discuss the recent results from these trials&#44; namely mucoactive&#44; anti-inflammatory and antibiotic therapy&#46; Several trials are ongoing and we hope they will be able to add clarification to the management of these patients&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As bronquiectasias n&#227;o-fibrose qu&#237;stica continuam a ser uma doen&#231;a respirat&#243;ria comum e importante&#46; Trata-se de uma patologia cr&#243;nica e&#44; consequentemente&#44; os doentes geralmente precisam de um tratamento cont&#237;nuo&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Nas &#250;ltimas d&#233;cadas&#44; tratamentos sem evid&#234;ncia cient&#237;fica dos seus benef&#237;cios foram comumente usadas nas bronquiectasias n&#227;o-fibrose qu&#237;stica&#46; A fibrose qu&#237;stica serviu de experi&#234;ncia para extrapolar a abordagem terap&#234;utica para outros doentes com bronquiectasias&#46; Finalmente&#44; nos &#250;ltimos anos&#44; foram realizados alguns ensaios bronquiectasias n&#227;o-fibrose qu&#237;stica que visam avaliar a efic&#225;cia de alguns dos tratamentos que s&#227;o comummente usados mas por vezes sem uma clara indica&#231;&#227;o&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Nesta revis&#227;o ser&#227;o apresentados os resultados recentes destes ensaios&#44; nomeadamente sobre o tratamento mucoactivo&#44; anti-inflamat&#243;rio e antibi&#243;tico&#46; Diversos estudos est&#227;o a decorrer e esperamos que estes venham a esclarecer a abordagem mais adequada destes doentes&#46;</p></span>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hyperosmolar agent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mannitol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hypertonic saline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400<span class="elsevierStyleHsp" style=""></span>mg bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 or 7&#37; bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Delivery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">By an inhaler&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">By nebulizer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Duration of effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sustained &#40;up to 24<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Short&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab884635.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Comparison between mannitol and hypertonic saline&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">BAT</span>&#58; Bronchiectasis and long-term Azithromycin Treatment&#59; <span class="elsevierStyleItalic">BLESS</span>&#58; Bronchiectasis and Low-dose Erythromycin Study&#59; <span class="elsevierStyleItalic">EMBRACE</span>&#58; Effectiveness of Macrolides in patients with BRonchiectasis using Azithromycin to Control Exacerbations&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&#59;Mean age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&#47;dosageMean duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Benefits&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse effects &#40;number of patients&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Koh et al&#46; &#40;1997&#41;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#59;13 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Roxithromycin&#58; 4<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#59;12 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Airway hyperresponsiveness&#8595; sputum purulence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not studied&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Tsang et al&#46; &#40;1999&#41;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#59;54&#46;3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Erythromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#59;8 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; EV<span class="elsevierStyleInf">1</span> and FVC&#59;&#8595; sputum volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rash &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Davies et al&#46; &#40;2004&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prospective&#44;open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39&#59;51&#46;9 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day 6 days&#44; followed by 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 6 days and later 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 3 days&#47;week&#59;&#62;4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Volume of sputum&#8595; Symptoms&#8595; Exacerbations&#8593; DLCO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea &#40;2&#41;&#59;abnormal liver function tests &#40;2&#41;&#59;rash &#40;1&#41;&#59;tinnitus &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Cymbala et al&#46; &#40;2005&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;open label&#44;crossover&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#59;71 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 2 days&#47;week&#59;6 months<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Volume of sputum&#8595; Exacerbations&#8593; General well-being&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Yalcin et al&#46; &#40;2006&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34&#59;12&#46;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clarithromycin&#58; 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#59;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; FEF<span class="elsevierStyleInf">25&#8211;75</span>&#8595; Volume of sputum&#8595; Inflammatory markers in BAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Anwar et al&#46; &#40;2008&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Retrospective&#44;open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#59;63 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 3 days&#47;week&#59;9&#46;1 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; FEV<span class="elsevierStyleInf">1</span>&#8595; Exacerbations&#8595; Sputum microbial isolates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea &#40;3&#41;abdominal cramps &#40;2&#41;&#59;skin rash &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Serisier et al&#46; &#40;2011&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prospective&#44;open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#59;62&#46;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Erythromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#59;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Exacerbations&#8595; Annual days of antibiotic use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nausea &#40;1&#41;Headache &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Alternburg et al&#46; &#40;2011&#41;BAT<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">89&#59;65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#59;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Exacerbations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Serisier et al&#46; &#40;2012&#41;BLESS<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#59;62&#46;3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Erythromycin&#58; 250<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#59;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Exacerbations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">QTc prolongation &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Wong et al&#46; &#40;2012&#41;EMBRACE<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Randomized&#44;double-blind&#44; placebo-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">141&#59;60 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#58; 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; 3 days&#47;week&#59;6 months<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>6 months follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8595; Rate of exacerbations&#8593; Time to first exacerbation&#8595; Blood neutrophils&#44; WBC and eosinophils&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Macrolide resistant <span class="elsevierStyleItalic">S&#46; pneumonia</span> &#40;2&#41;Gastrointestinal symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab884634.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Clinical trials of macrolide therapy&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:88 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;A&#46; Floto"
                            1 => "C&#46;S&#46; Haworth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Eur Respir Mon"
                        "fecha" => "2011"
                        "paginaInicial" => "52"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;L&#46; Metersky"
                            1 => "A&#46;E&#46; O&#8217;Donnel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Clin Chest Med"
                        "fecha" => "2012"
                        "paginaInicial" => "33"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "British Thoracic Society guideline for non-CF bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;C&#46; Pasteur"
                            1 => "D&#46; Bilton"
                            2 => "A&#46;T&#46; Hill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2010.136119"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2010"
                        "volumen" => "65"
                        "paginaInicial" => "i1"
                        "paginaFinal" => "i58"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20627931"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis and Treatment of Bronchiectasis&#46; Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Vendrell"
                            1 => "J&#46; De Gracia"
                            2 => "C&#46; Oliveira"
                            3 => "M&#46;A&#46; Mart&#237;nez"
                            4 => "R&#46; Gir&#243;n"
                            5 => "L&#46; M&#225;iz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2008"
                        "volumen" => "44"
                        "paginaInicial" => "629"
                        "paginaFinal" => "640"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19007570"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Evaluating success of therapy for bronchiectasis&#46; What end points to use&#63;"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ccm.2012.03.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chest Med"
                        "fecha" => "2012"
                        "volumen" => "33"
                        "paginaInicial" => "329"
                        "paginaFinal" => "349"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22640849"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucins&#44; mucus&#44; and sputum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;A&#46; Voynow"
                            1 => "B&#46;K&#46; Rubin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.08-0412"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2009"
                        "volumen" => "135"
                        "paginaInicial" => "505"
                        "paginaFinal" => "512"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19201713"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucoactive agents for airway mucus hypersecretory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46; Rogers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Care"
                        "fecha" => "2007"
                        "volumen" => "52"
                        "paginaInicial" => "1176"
                        "paginaFinal" => "1198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17716385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New concepts of the pathogenesis of cystic fibrosis lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;C&#46; Boucher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2004"
                        "volumen" => "23"
                        "paginaInicial" => "146"
                        "paginaFinal" => "158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14738247"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0016508597001273"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis&#58; effect on lung function&#44; health status and sputum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Daviskas"
                            1 => "S&#46;D&#46; Anderson"
                            2 => "K&#46; Gomes"
                            3 => "P&#46; Briffa"
                            4 => "B&#46; Cochrane"
                            5 => "H&#46;K&#46; Chan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1843.2005.00659.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respirology"
                        "fecha" => "2005"
                        "volumen" => "10"
                        "paginaInicial" => "46"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15691238"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46;T&#46; King"
                            1 => "E&#46; Daviskas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Breathe"
                        "fecha" => "2010"
                        "volumen" => "6"
                        "paginaInicial" => "353"
                        "paginaFinal" => "360"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled mannitol in the treatment of non-cystic fibrosis bronchiectasis in adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Gjoerup"
                            1 => "O&#46; Hilberg"
                            2 => "E&#46; Bendstrup"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1843.2012.02189.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respirology"
                        "fecha" => "2012"
                        "volumen" => "17"
                        "paginaInicial" => "927"
                        "paginaFinal" => "932"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22564014"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Bronchitol<span class="elsevierStyleSup">&#174;</span> Pharmaxis Pharmaceuticals Ltd&#46; European Medicines Agency"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Daviskas"
                            1 => "S&#46;D&#46; Anderson"
                            2 => "S&#46; Eberl"
                            3 => "H&#46;K&#46; Chan"
                            4 => "I&#46;H&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2001"
                        "volumen" => "119"
                        "paginaInicial" => "414"
                        "paginaFinal" => "421"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11171717"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled dry-powder mannitol in cystic fibrosis&#58; an efficacy and safety study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "D&#46; Bilton"
                            1 => "P&#46; Robinson"
                            2 => "P&#46; Cooper"
                            3 => "C&#46;G&#46; Gallagher"
                            4 => "J&#46; Kolbe"
                            5 => "H&#46; Fox"
                            6 => "CF301 Study Investigators"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00187510"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2011"
                        "volumen" => "38"
                        "paginaInicial" => "1071"
                        "paginaFinal" => "1080"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21478216"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized placebo-controlled trial of inhaled mannitol in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Bilton"
                            1 => "E&#46; Daviskas"
                            2 => "A&#46; Jacques"
                            3 => "S&#46;D&#46; Anderson"
                            4 => "B&#46; Charlton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "179"
                        "paginaInicial" => "A3221"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "A Phase III Multicenter&#44; Randomized&#44; Parallel Group&#44; Controlled&#44; Double Blind Study to Investigate the Safety and Efficacy of Inhaled Mannitol Over 12 Months in the Treatment of Bronchiectasis"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Elkins"
                            1 => "M&#46; Robinson"
                            2 => "B&#46;R&#46; Rose"
                            3 => "C&#46; Harbour"
                            4 => "C&#46;P&#46; Moriarty"
                            5 => "B&#46; Guy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa043900"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "229"
                        "paginaFinal" => "240"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16421364"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nebulised hypertonic saline for cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Wark"
                            1 => "V&#46;M&#46; McDonld"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD001506.pub3"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2009"
                        "volumen" => "2"
                        "paginaInicial" => "CD001506"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19370568"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of nebulised hypertonic saline &#40;7&#37;&#41; as an adjunct to physiotherapy in patients with stable bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46; Kellet"
                            1 => "J&#46; Redfern"
                            2 => "R&#46; Mcl Niven"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2005"
                        "volumen" => "99"
                        "paginaInicial" => "27"
                        "paginaFinal" => "31"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15672845"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nebulised 7&#37; hypertonic saline improves lung function and quality of life in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Kellet"
                            1 => "N&#46;M&#46; Robert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2011.07.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2011"
                        "volumen" => "105"
                        "paginaInicial" => "1831"
                        "paginaFinal" => "1835"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22018993"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The long term effect of inhaled hypertonic saline 6&#37; in non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;H&#46;H&#46; Nicolson"
                            1 => "R&#46;G&#46; Stirling"
                            2 => "B&#46;M&#46; Borg"
                            3 => "B&#46;M&#46; Button"
                            4 => "J&#46;W&#46; Wilson"
                            5 => "A&#46;E&#46; Holland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2011.12.021"
                      "Revista" => array:7 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2012"
                        "volumen" => "106"
                        "paginaInicial" => "661"
                        "paginaFinal" => "667"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22349069"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673605663787"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical utility of long-term humidification therapy in chronic airway disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Rea"
                            1 => "S&#46; McAuley"
                            2 => "L&#46; Jayaram"
                            3 => "J&#46; Garrett"
                            4 => "H&#46; Hockey"
                            5 => "L&#46; Storey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2009.12.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2010"
                        "volumen" => "104"
                        "paginaInicial" => "525"
                        "paginaFinal" => "533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20144858"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucoactive agents for airway mucus hypersecretory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;F&#46; Rogers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Care"
                        "fecha" => "2007"
                        "volumen" => "52"
                        "paginaInicial" => "1176"
                        "paginaFinal" => "1197"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17716385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucolytics for bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;J&#46; Crockett"
                            1 => "J&#46;M&#46; Cranston"
                            2 => "K&#46;M&#46; Latimer"
                            3 => "K&#46;M&#46; Latiner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD001289"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2001"
                        "volumen" => "1"
                        "paginaInicial" => "CD001289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11279712"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;E&#46; O&#8217;Donnel"
                            1 => "A&#46;F&#46; Barker"
                            2 => "J&#46;S&#46; Ilowite"
                            3 => "R&#46;B&#46; Fick"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1998"
                        "volumen" => "113"
                        "paginaInicial" => "1329"
                        "paginaFinal" => "1334"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9596315"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;E&#46; O&#8217;Donnell"
                            1 => "Bronchiectasis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.08-0776"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2008"
                        "volumen" => "134"
                        "paginaInicial" => "815"
                        "paginaFinal" => "823"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18842914"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammation&#58; a two-edged sword&#8212;the model of bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;J&#46; Cole"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Respir Dis Suppl"
                        "fecha" => "1986"
                        "volumen" => "147"
                        "paginaInicial" => "6"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3533593"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchial inflammation and colonization in patients with clinically stable bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Angrill"
                            1 => "R&#46; de Celis"
                            2 => "F&#46; Arancibia"
                            3 => "X&#46; Filella"
                            4 => "A&#46; Ra&#241;&#243;"
                            5 => "M&#46; Elena"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.164.9.2105083"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2001"
                        "volumen" => "164"
                        "paginaInicial" => "1628"
                        "paginaFinal" => "1632"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11719301"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunomodulatory effects of macrolide antibiotics&#8212;Part 1&#58; Biological mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Altenburg"
                            1 => "C&#46;S&#46; De Graaff"
                            2 => "T&#46;S&#46; Van der Werf"
                            3 => "W&#46;G&#46; Boersma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000320319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respiration"
                        "fecha" => "2011"
                        "volumen" => "81"
                        "paginaInicial" => "67"
                        "paginaFinal" => "74"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20733281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunomodulatory effects of macrolide antibiotics&#8212;Part 2&#58; Advantages and disadvantages of long-term&#44; low-dose macrolide therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Altenburg"
                            1 => "C&#46;S&#46; De Graaff"
                            2 => "T&#46;S&#46; Van der Werf"
                            3 => "W&#46;G&#46; Boersma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000320320"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respiration"
                        "fecha" => "2011"
                        "volumen" => "81"
                        "paginaInicial" => "75"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20733282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Macrolides beyond the conventional antimicrobials&#58; a class of potent immunomodulators"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "E&#46;J&#46; Giamarellos-Bourboulis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijantimicag.2007.08.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Antimicrob Agents"
                        "fecha" => "2008"
                        "volumen" => "31"
                        "paginaInicial" => "12"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17935949"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Usefulness of macrolides as anti-inflammatories in respiratory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46; Sevilla-S&#225;nchez"
                            1 => "D&#46; Soy-Muner"
                            2 => "N&#46; Soler-Porcar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arbres.2009.10.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2010"
                        "volumen" => "46"
                        "paginaInicial" => "244"
                        "paginaFinal" => "254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19962815"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of roxithromycin on airway responsiveness in children with bronchiectasis&#58; a double-blind&#44; placebo-controlled study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Y&#46;Y&#46; Koh"
                            1 => "M&#46;H&#46; Lee"
                            2 => "Y&#46;H&#46; Sun"
                            3 => "K&#46;W&#46; Sung"
                            4 => "J&#46;H&#46; Chae"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1997"
                        "volumen" => "10"
                        "paginaInicial" => "994"
                        "paginaFinal" => "999"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9163637"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pilot study of low-dose erythromycin in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;W&#46; Tsang"
                            1 => "P&#46;I&#46; Ho"
                            2 => "K&#46;N&#46; Chan"
                            3 => "M&#46;S&#46;M&#46; Ip"
                            4 => "W&#46;K&#46; Lam"
                            5 => "C&#46;S&#46; Ho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "13"
                        "paginaInicial" => "361"
                        "paginaFinal" => "364"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10065682"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prophylactic antibiotic treatment of bronchiectasis with azithromycin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Davies"
                            1 => "R&#46; Wilson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "540"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15170048"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;A&#46; Cymbala"
                            1 => "L&#46;C&#46; Edmonds"
                            2 => "M&#46;A&#46; Bauer"
                            3 => "P&#46;J&#46; Jederlinic"
                            4 => "J&#46;J&#46; May"
                            5 => "J&#46;M&#46; Victory"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Treat Respir Med"
                        "fecha" => "2005"
                        "volumen" => "4"
                        "paginaInicial" => "117"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15813663"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Yalcin"
                            1 => "N&#46; Kiper"
                            2 => "U&#46; Ozcelik"
                            3 => "D&#46; Do&#287;ru"
                            4 => "P&#46; F&#305;rat"
                            5 => "A&#46; &#350;ahin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2710.2006.00708.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Pharm Ther"
                        "fecha" => "2006"
                        "volumen" => "31"
                        "paginaInicial" => "49"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16476120"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46;A&#46; Anwar"
                            1 => "S&#46;C&#46; Bourke"
                            2 => "G&#46; Afolabi"
                            3 => "P&#46; Middleton"
                            4 => "C&#46; Ward"
                            5 => "R&#46;M&#46; Rutherford"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2008.06.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2008"
                        "volumen" => "102"
                        "paginaInicial" => "1494"
                        "paginaFinal" => "1496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18653323"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term&#44; low-dose erythromycin in bronchiectasis subjects with frequent infective exacerbations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;J&#46; Serisier"
                            1 => "M&#46;L&#46; Martin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2011.01.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2011"
                        "volumen" => "105"
                        "paginaInicial" => "946"
                        "paginaFinal" => "949"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21367595"
                             …1
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term azithromycin treatment&#58; a randomized placebo-controlled trial in non-CF bronchiectasis&#59; results from the BAT trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2011"
                        "volumen" => "36"
                        "numero" => "Suppl&#46; 54"
                        "paginaInicial" => "333s"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Bronchiectasis and Low-dose Erythromycin Study &#40;BLESS&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2012"
                        "volumen" => "185"
                        "numero" => "May &#40;1 Meeting Abstracts&#41;"
                        "paginaInicial" => "A68624"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis &#40;EMBRACE&#41;&#58; a randomised&#44; double-blind&#44; placebo-controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)60953-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "380"
                        "paginaInicial" => "660"
                        "paginaFinal" => "667"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arbres.2011.06.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2011"
                        "volumen" => "47"
                        "paginaInicial" => "599"
                        "paginaFinal" => "609"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Med J Aust"
                        "fecha" => "2010"
                        "volumen" => "193"
                        "paginaInicial" => "356"
                        "paginaFinal" => "365"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled steroids for bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD000996.pub2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2009"
                        "volumen" => "1"
                        "paginaInicial" => "CD000996"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical efficacy and safety of budesonide-formoterol in non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.11-0180"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2012"
                        "volumen" => "141"
                        "paginaInicial" => "461"
                        "paginaFinal" => "468"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of high-dose ibuprofen in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199503303321303"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1995"
                        "volumen" => "332"
                        "paginaInicial" => "848"
                        "paginaFinal" => "854"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD001505.pub2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                        "volumen" => "4"
                        "paginaInicial" => "CD001505"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral non steroid anti-inflammatories for children and adults with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD006427.pub2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                        "volumen" => "4"
                        "paginaInicial" => "CD006427"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled non-steroid anti-inflammatories for children and adults with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD007525.pub2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2010"
                        "volumen" => "4"
                        "paginaInicial" => "CD007525"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0016508502334140"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pharmthera.2009.06.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacol Ther"
                        "fecha" => "2009"
                        "volumen" => "124"
                        "paginaInicial" => "86"
                        "paginaFinal" => "95"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lovastatin enhances clearance of apoptotic cells &#40;efferocytosis&#41; with implications for chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2006"
                        "volumen" => "176"
                        "paginaInicial" => "7657"
                        "paginaFinal" => "7665"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Burying the dead&#58; the impact of failed apoptotic cell removal &#40;efferocytosis&#41; on chronic inflammatory lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.129.6.1673"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2006"
                        "volumen" => "129"
                        "paginaInicial" => "1673"
                        "paginaFinal" => "1682"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Atorvastatin in bronchiectasis in patients with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "A trial of atorvastatin as an anti-inflammatory agent in non-cystic fibrosis bronchiectasis"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leukotriene receptor antagonists for non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2000"
                        "paginaInicial" => "CD002174"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral methylxanthines for bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2001"
                        "paginaInicial" => "CD002734"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "The effect of theophylline in the treatment of bronchiectasis"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "The role of theophylline plus low-dose formoterol-budesonide in treatment of bronchiectasis&#46; ClinicalTrials&#46;gov&#46; Trial identifier&#58; <a href="ctgov:NCT01769898">NCT01769898</a>&#46;"
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobial therapy for pulmonar pathogenic colonisation and infection by <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in cystic fibrosis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1469-0691.2005.01217.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Microbiol Infect"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "paginaInicial" => "690"
                        "paginaFinal" => "703"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bacterial colonisation in patients with bronchiectasis&#58; microbiological pattern and risk factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2002"
                        "volumen" => "57"
                        "paginaInicial" => "15"
                        "paginaFinal" => "19"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An investigation into causative factors in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.162.4.9906120"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "162"
                        "paginaInicial" => "1277"
                        "paginaFinal" => "1284"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2002"
                        "volumen" => "57"
                        "paginaInicial" => "935"
                        "paginaFinal" => "938"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paediatric bronchiectasis in the twenty-first century&#58; experience of a tertiary children&#39;s hospital in New Zealand"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Paediatr Child Health"
                        "fecha" => "2003"
                        "volumen" => "39"
                        "paginaInicial" => "111"
                        "paginaFinal" => "117"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The need to redefine non-cystic fibrosis bronchiectasis in childhood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "324"
                        "paginaFinal" => "327"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determinants of chronic infection with <span class="elsevierStyleItalic">Staphylococcus aureus</span> in patients with bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "14"
                        "paginaInicial" => "1340"
                        "paginaFinal" => "1344"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathogen&#8211;host interactions in <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> pneumonia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200408-1044SO"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "171"
                        "paginaInicial" => "1209"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neutrophil apoptosis&#44; proinflammatory mediators and cell counts in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "231"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differences in biofilm development and antibiotic susceptibility among <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> isolates from cystic fibrosis samples and blood cultures"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jac/dkl482"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Antimicrob Chemother"
                        "fecha" => "2007"
                        "volumen" => "59"
                        "paginaInicial" => "301"
                        "paginaFinal" => "304"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Normativa del diagn&#243;stico y el tratamento de la afecci&#243;n respirat&#243;ria en la fibrosis qu&#237;stica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2001"
                        "volumen" => "37"
                        "paginaInicial" => "316"
                        "paginaFinal" => "324"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparative study on the efficacy of levofloxacin and ceftazidime in acute exacerbation of bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "14"
                        "paginaInicial" => "1206"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infection in adult bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.130.5.1503"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2006"
                        "volumen" => "130"
                        "paginaInicial" => "1503"
                        "paginaFinal" => "1510"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra012519"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2002"
                        "volumen" => "346"
                        "paginaInicial" => "1383"
                        "paginaFinal" => "1393"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.07-0490"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2007"
                        "volumen" => "132"
                        "paginaInicial" => "1565"
                        "paginaFinal" => "1572"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of PSAE infection on clinical parameters in steady-state bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1998"
                        "volumen" => "114"
                        "paginaInicial" => "1594"
                        "paginaFinal" => "1598"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antibiotic strategies for eradicating <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in people with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2006"
                        "paginaInicial" => "CD001392"
                        "itemHostRev" => array:3 [
                          "pii" => "S001650850701918X"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breakpoints for predicting <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> susceptibility to inhaled tobramycin in cystic fibrosis patients&#58; use of high-range Etest strips"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.43.9.4480-4485.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2005"
                        "volumen" => "43"
                        "paginaInicial" => "4480"
                        "paginaFinal" => "4485"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prolonged antibiotics for purulent bronchiectasis in children and adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                        "paginaInicial" => "CD001392"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Utilidad de los antibi&#243;ticos inalados&#58; m&#225;s all&#225; de la fibrosis qu&#237;stica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Neumol Pediatr"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "119"
                        "paginaFinal" => "122"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tobramycin solution for inhalation reduces sputum <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> density in bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.162.2.9910086"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "162"
                        "paginaInicial" => "481"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201005-0756OC"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2011"
                        "volumen" => "183"
                        "paginaInicial" => "491"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment with tobramycin solution for inhalation in bronchiectasis with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2001"
                        "volumen" => "120"
                        "paginaInicial" => "114s"
                        "paginaFinal" => "117s"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1345/aph.1E099"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Pharmacother"
                        "fecha" => "2005"
                        "volumen" => "39"
                        "paginaInicial" => "39"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.127.4.1420"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2005"
                        "volumen" => "127"
                        "paginaInicial" => "1420"
                        "paginaFinal" => "1426"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of long term nebulized colistin on lung function and quality of life in patients with chronic bronchial sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1445-5994.2007.01404.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intern Med J"
                        "fecha" => "2007"
                        "volumen" => "37"
                        "paginaInicial" => "495"
                        "paginaFinal" => "498"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled liposomal ciprofloxacin hydrochloride significantly reduces sputum <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> density in CF and non-CF bronchiectasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "179"
                        "paginaInicial" => "A3214"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de las bronquiectasias no debidas a fibrosis qu&#237;stica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arbres.2011.06.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2011"
                        "volumen" => "47"
                        "paginaInicial" => "599"
                        "paginaFinal" => "609"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de las bronchiectasias no fibrosis qu&#237;stica en fase estable"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Neumosur"
                        "fecha" => "2006"
                        "volumen" => "18"
                        "paginaInicial" => "143"
                        "paginaFinal" => "150"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/08732159/0000001900000006/v2_201509041406/S0873215913000536/v2_201509041406/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "9597"
    "tipo" => "SECCION"
    "pt" => array:2 [
      "titulo" => "Revis&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "pt"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/08732159/0000001900000006/v2_201509041406/S0873215913000536/v2_201509041406/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215913000536?idApp=UINPBA00004E"
]
Article information
ISSN: 08732159
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 25 5 30
2024 October 118 33 151
2024 September 108 34 142
2024 August 113 33 146
2024 July 118 37 155
2024 June 82 37 119
2024 May 99 30 129
2024 April 96 34 130
2024 March 80 31 111
2024 February 123 31 154
2024 January 87 27 114
2023 December 80 34 114
2023 November 99 40 139
2023 October 69 55 124
2023 September 63 36 99
2023 August 98 27 125
2023 July 92 30 122
2023 June 61 27 88
2023 May 92 28 120
2023 April 75 20 95
2023 March 156 24 180
2023 February 95 22 117
2023 January 45 23 68
2022 December 79 34 113
2022 November 107 35 142
2022 October 81 33 114
2022 September 24 30 54
2022 August 44 31 75
2022 July 40 51 91
2022 June 30 27 57
2022 May 44 37 81
2022 April 63 27 90
2022 March 60 50 110
2022 February 68 39 107
2022 January 84 39 123
2021 December 27 59 86
2021 November 42 36 78
2021 October 42 35 77
2021 September 38 31 69
2021 August 49 25 74
2021 July 28 14 42
2021 June 37 29 66
2021 May 55 27 82
2021 April 212 59 271
2021 March 146 22 168
2021 February 117 32 149
2021 January 98 24 122
2020 December 48 15 63
2020 November 75 25 100
2020 October 69 10 79
2020 September 100 29 129
2020 August 120 30 150
2020 July 138 36 174
2020 June 106 20 126
2020 May 116 19 135
2020 April 151 17 168
2020 March 149 23 172
2020 February 135 21 156
2020 January 144 26 170
2019 December 133 49 182
2019 November 239 35 274
2019 October 246 35 281
2019 September 261 39 300
2019 August 349 38 387
2019 July 403 32 435
2019 June 458 41 499
2019 May 453 46 499
2019 April 513 55 568
2019 March 485 49 534
2019 February 352 13 365
2019 January 302 37 339
2018 December 194 10 204
2018 November 60 3 63
2018 October 103 9 112
2018 September 51 6 57
2018 August 60 34 94
2018 July 57 28 85
2018 June 120 26 146
2018 May 376 29 405
2018 April 234 46 280
2018 March 251 30 281
2018 February 150 17 167
2018 January 186 28 214
2017 December 175 19 194
2017 November 182 24 206
2017 October 134 27 161
2017 September 151 31 182
2017 August 149 32 181
2017 July 112 45 157
2017 June 113 18 131
2017 May 200 31 231
2017 April 106 10 116
2017 March 207 32 239
2017 February 192 9 201
2017 January 63 14 77
2016 December 92 14 106
2016 November 217 10 227
2016 October 214 16 230
2016 September 241 21 262
2016 August 127 18 145
2016 July 134 39 173
2016 June 5 26 31
2016 May 12 51 63
2016 April 298 9 307
2016 March 430 80 510
2016 February 417 62 479
2016 January 434 65 499
2015 December 392 56 448
2015 November 414 63 477
2015 October 452 74 526
2015 September 368 54 422
2015 August 424 67 491
2015 July 454 49 503
2015 June 321 32 353
2015 May 365 44 409
2015 April 475 39 514
2015 March 665 23 688
2015 February 635 20 655
2015 January 589 24 613
2014 December 502 34 536
2014 November 435 31 466
2014 October 564 35 599
2014 September 479 51 530
2014 August 390 31 421
2014 July 373 25 398
2014 June 323 25 348
2014 May 320 40 360
2014 April 322 39 361
2014 March 408 73 481
2014 February 303 59 362
2014 January 277 75 352
2013 December 166 79 245
2013 November 134 109 243
Show all

Follow this link to access the full text of the article

Pulmonology

Are you a health professional able to prescribe or dispense drugs?