Editorial
About the role of indacaterol in obstructive airways disorder: PRO
A propósito do papel do Indacaterol na patologia obstrutiva das vias aéreas: PRÓ
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Drummond" "autores" => array:1 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Drummond" "email" => array:1 [ 0 => "marta.drummond@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Assistente Hospitalar de Pneumologia do Hospital de São João, Porto, Portugal" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Docente da Faculdade de Medicina da Universidade do Porto, Porto, Portugal" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "A propósito do papel do Indacaterol na patologia obstrutiva das vias aéreas: PRÓ" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic Obstructive Pulmonary Disease (COPD) is a major cause of mortality and chronic morbidity throughout the world.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">COPD is nowadays the fourth leading cause of death<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and its mortality is estimated to increase in the coming decades.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Most studies have indicated that the existing pharmacologic treatment for COPD do not modify the long-term decline of pulmonary function,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> so pharmacotherapy is mainly used to decrease symptoms and/or complications.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Bronchodilator medications are central to the symptomatic management of COPD and β2 agonists are recommended in all stages of severity of COPD.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">As with all chronic diseases, non-adherence to treatment is common in patients with COPD.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> More complex regimens generally result in suboptimal adherence, with dosing and the absence of immediate effect on symptoms regarded as the principal factors negatively influencing adherence.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Indacaterol is an innovative, inhaled, ultra-long acting β2 agonist that has been approved in more than 50 countries worldwide, including throughout the European Union at the doses 150<span class="elsevierStyleHsp" style=""></span>μg and 300<span class="elsevierStyleHsp" style=""></span>μg once-daily for COPD treatment.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">This molecule is the result of bio-engineering, being highly lipophilic, a property that allows a longer and more stable association with membrane β2-receptors,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> resulting in an ultra-long duration of action, similar to salmeterol and tiotropium.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> Furthermore, this strong interaction results in a rapid citoplasmatic molecule activation leading to rapid onset bronchodilation. In preclinical studies, the onset of action of indacaterol was similar to that of salbutamol and formoterol,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> a result confirmed by clinical trials.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The efficacy of indacaterol in the maintenance treatment of COPD in adults has been assessed in four fully published, large (>400 patients), randomized, double-blind parallel-group, placebo-controlled, multicentre, phase III trials.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,15–17</span></a> The primary endpoint in the four placebo-controlled trials was the 24-h post-dose FEV1 after 12 weeks.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In the INHANCE study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> both doses of indacaterol achieved higher post-dose FEV1 values (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.01) than tiotropium 18<span class="elsevierStyleHsp" style=""></span>μg once-daily, with absolute differences of 40–50<span class="elsevierStyleHsp" style=""></span>ml between the former and the latter. Furthermore, when dividing patients into subgroups such as age under/over 65; non/current smokers and non/inhaled corticosteroids users, indacaterol (both doses) was non-inferior to tiotropium in all subgroups.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The INVOLVE<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and INLIGHT<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> studies, suggested that indacaterol 300<span class="elsevierStyleHsp" style=""></span>μg once daily was significantly (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.001) more effective than formoterol 12<span class="elsevierStyleHsp" style=""></span>μg twice daily,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and indacaterol 150<span class="elsevierStyleHsp" style=""></span>μg once daily was significantly (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) more effective than salmeterol 50<span class="elsevierStyleHsp" style=""></span>μg twice daily,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> as measured by 24-h post-dose FEV1 at 12 weeks.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Furthermore, it has been proven that indacaterol leads to a reduction in rescue medication when compared to formoterol<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and tiotropium.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> More recently, the INTENSITY study<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> revealed a great reduction in rescue medication use with indacaterol over tiotropium, with patients on indacaterol experiencing an additional 5% of days free from rescue medication use.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Regarding quality of life (QoL), three studies<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,15,17</span></a> were designed and performed to compare the QoL impact of indacaterol. This impact was assessed using St. George's Respiratory Questionnaire (SGRQ).</p><p id="par0065" class="elsevierStylePara elsevierViewall">In the INHANCE study,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> mean SGRQ total scores versus placebo were significantly greater for indacaterol 150<span class="elsevierStyleHsp" style=""></span>μg once daily, but not for 300<span class="elsevierStyleHsp" style=""></span>μg recipients than for tiotropium ones after 26 therapy weeks.</p><p id="par0070" class="elsevierStylePara elsevierViewall">SGRQ score versus placebo was also significantly greater for indacaterol than for salmeterol recipients at 12-week assessment in INLIGHT study.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In INVOLVE study,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> there were no significant differences between indacaterol and formoterol at 12 and 52 week assessments, in what concerns QoL.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Limitation in exercise capacity represents an important feature of COPD, and is one of the main factors which have a negative impact on patient quality of life. O’Donnell et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> have already demonstrated that indacaterol achieved a significant improvement in end-exercise inspiratory capacity after 3 weeks of treatment with a difference from placebo of 280<span class="elsevierStyleHsp" style=""></span>ml. Improvement in exercise endurance time was also higher with indacaterol than with placebo. This observed exercise capacity amelioration with indacaterol could be explained by the improved health status observed in long-term studies<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,15</span></a> assessed using SGRQ.</p><p id="par0085" class="elsevierStylePara elsevierViewall">In cases of use of short-term β2-agonist in patients undergoing long acting β2-agonists (LABA), none of the indacaterol doses caused a change in isoprenaline-induced relaxation. In contrast, even the lowest concentration of salmeterol significantly antagonized the effects of isoprenaline.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">It has been suggested that a partial agonist such as salmeterol has to occupy more receptors than a full agonist and thereby creates a situation in which functional receptor number becomes limiting in terms of obtaining a maximal response. As a consequence, a partial agonist behaves as an antagonist in the presence of an agonist with higher efficacy acting on the same receptor.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Data regarding rates of exacerbations are limited, but INHANCE study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> showed that they were similar between both doses of indacaterol and tiotropium, and lower than observed in placebo group.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In relation to adverse events, INHANCE study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> showed that this events occurred in similar percentages of patients across all treatment groups (indacaterol 150 and 300<span class="elsevierStyleHsp" style=""></span>μg, placebo and tiotropium 18<span class="elsevierStyleHsp" style=""></span>μg) in the 26-week study period. Adverse events were typical of those expected in patients with moderate or severe COPD and were predominantly of mild or moderate severity. The most frequent adverse events were respiratory tract infections which occurred in similar numbers of patients in each treatment group.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,18</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The INLIGHT study<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> provided further evidence of the favorable safety profile of indacaterol 150<span class="elsevierStyleHsp" style=""></span>μg once daily. During this study, adverse events occurred in similar numbers of patients in indacaterol (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>104, 49.3%) and placebo groups (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>96, 46.8%). The most frequent individual events were COPD worsening and cough, both of which occurred more frequently with placebo than with indacaterol.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In INSURE study,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> adverse events were reported in 3/86 (3.5%), 3/87 (3.4%), 4/86 (4.7%), 6/88 (6.8%), and 4/87 (4.6%) patients taking indacaterol 150<span class="elsevierStyleHsp" style=""></span>μg, indacaterol 300<span class="elsevierStyleHsp" style=""></span>μg, salbutamol 200<span class="elsevierStyleHsp" style=""></span>μg, salmeterol–fluticasone 50/500<span class="elsevierStyleHsp" style=""></span>μg, and placebo, respectively. All reported adverse events were mild or moderate in severity. There were no deaths and no patient discontinued from the study due to adverse events.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Another study<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> has already demonstrated an acceptable tolerability and safety profile of indacaterol even with the above-therapeutic 600<span class="elsevierStyleHsp" style=""></span>μg doses given for up to 1 year, compared with placebo.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In phase III clinical studies,<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> health care providers observed that at clinic visits on average 17–20% of patients experienced sporadic cough that occurred usually within 15<span class="elsevierStyleHsp" style=""></span>s following inhalation and typically lasted for 5<span class="elsevierStyleHsp" style=""></span>s. This cough experienced post-inhalation was generally well tolerated and did not lead to any patient discontinuing the studies at the recommended doses. There is no evidence that cough experienced post-inhalation is associated with bronchospasm, exacerbations, deteriorations of disease or loss of efficacy. In the phase III trials, the incidence of cough spontaneously reported by patients as an adverse event was approximately 7% for indacaterol with no clear dose response versus 5% for placebo. This compares to 6% on tiotropium and 4% on formoterol.</p><p id="par0125" class="elsevierStylePara elsevierViewall">The patient reports on cough were fewer than health care professionals have noticed, which shows the lack of importance patients gave to this episode.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Work<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> was carried out to identify the aetiology of cough experienced following inhalation, but so far has not provided conclusive results and further research is ongoing to elucidate its mechanism.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Finally, a word about Breezhaler<span class="elsevierStyleSup">®</span>. It is a new capsule based dry-powder inhaler with low resistance (0.07<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleSup">1/2</span>/l/min), specially created to be used with indacaterol.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a> This low resistance device is therefore suitable for use by patients with a wide range of COPD severities (including GOLD IV patients), making it possible to deliver a consistent fine particle dose irrespective of disease severity and age.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">There are no reports about device failures in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Furthermore, it is a small and very portable device preferred by many patients as their continued daily use inhaler.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In an open-label, randomized, cross-over study, patients found Breezhaler<span class="elsevierStyleSup">®</span> more comfortable to inhale through and simpler to use than Handihaler<span class="elsevierStyleSup">®</span>.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Patients were also more confident that the medication had been taken correctly using this inhaler<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> because they could hear the capsule spinning when inhaling, taste the lactose and see that the capsule, which is transparent, was empty after the procedure.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> So, this device has additional security mechanisms to assure patients a correct drug delivery.</p><p id="par0150" class="elsevierStylePara elsevierViewall">To summarize, indacaterol is rapid onset action, ultra-long acting, effective, safe and well-tolerated therapy for COPD patients. It is provided in a very portable, low resistance device, already preferred by many patients.</p><p id="par0155" class="elsevierStylePara elsevierViewall">These characteristics may make the difference in achieving better rates of therapy adherence in these chronic patients. So, in my opinion this therapy tool should be considered when prescribing bronchodilators to COPD patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Drummond, M. A propósito do papel do Indacaterol na patologia obstrutiva das vias aéreas: PRÓ. Rev Port Pneumol. 2012. <span class="elsevierStyleInterRef" href="doi:10.1016/j.rppneu.2011.10.002">doi 10.1016/j.rppneu.2011.10.002</span>.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "GOLD, strategy for diagnosis, management, and prevention of COPD. 2010." ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "World Health Report. Geneva. World Health Organization 2000. Chronic obstructive pulmonary disease: current burden and future projections" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.D. Lopez" 1 => "K. Shibuya" 2 => "C. Rao" 3 => "C.D. Mathers" 4 => "A.L. Hansell" 5 => "L.S. Held" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.06.00025805" "Revista" => array:7 [ "tituloSerie" => "Eur Respir J" "fecha" => "2006" "volumen" => "27" "paginaInicial" => "397" "paginaFinal" => "412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16452599" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109711033390" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking, Eur resp Soc Study on Chronic Obstructive Pulmonary Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.A. Pauwels" 1 => "C.G. Lofdahl" 2 => "L.A. Laitinen" 3 => "J.P. Schouten" 4 => "D.S. Postma" 5 => "N.B. Pride" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199906243402503" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1999" "volumen" => "340" "paginaInicial" => "1948" "paginaFinal" => "1953" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10379018" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomised, double blind placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.S. Burge" 1 => "P.M. Calverley" 2 => "P.W. Jones" 3 => "S. Spencer" 4 => "J.A. Anderson" 5 => "T.K. Maslen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "BMJ" "fecha" => "2000" "volumen" => "320" "paginaInicial" => "1297" "paginaFinal" => "1303" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10807619" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109708018330" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of Indacaterol on exercise endu-rance and lung hyperinflation in COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "O’Donnell" 1 => "R. Casaburi" 2 => "W. Vincken" 3 => "L. Puente-Maestu" 4 => "D. Swales" 5 => "B. Kramer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rmed.2011.03.014" "Revista" => array:6 [ "tituloSerie" => "Respiratory Medicine" "fecha" => "2011" "volumen" => "105" "paginaInicial" => "1030" "paginaFinal" => "1036" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21498063" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variations in patients‘adherence to medical recommendations: A quantitative review of 50 years of rese-arch" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.R. DiMatteo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Med Care" "fecha" => "2004" "volumen" => "42" "paginaInicial" => "200" "paginaFinal" => "209" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15076819" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0300893211008864" "estado" => "S300" "issn" => "03008932" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization. Adherence to long-term therapies: policy for action. Meeting report 2001 Jun 4-5." ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Indacaterol in Chronic Obstructive Pulmonary Dise-ase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.D. Moen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2165/11203960-000000000-00000" "Revista" => array:7 [ "tituloSerie" => "Drugs" "fecha" => "2010" "volumen" => "70" "paginaInicial" => "2269" "paginaFinal" => "2280" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21080743" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1053077010000406" "estado" => "S300" "issn" => "10530770" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta 2-adrenoceptor agonist bronchodilator" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.P. Anderson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Life Sci" "fecha" => "1993" "volumen" => "52" "paginaInicial" => "2145" "paginaFinal" => "2160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8099696" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109712000022" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Once-daily bronchodilators for Chronic Obstructive Pulmonary Disease- Indacaterol versus Tiotropium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.F. Donohue" 1 => "C. Fogarty" 2 => "J. Lotvall" 3 => "D.A. Mahler" 4 => "H. Worth" 5 => "A. Yorgancioglu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200910-1500OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2010" "volumen" => "182" "paginaInicial" => "155" "paginaFinal" => "162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20463178" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "24-hour bronchodilator efficacy of single doses of inda-caterol in subjects with COPD: comparison with placebo and formoterol" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. Bauwens" 1 => "V. Ninane" 2 => "B. Van de Maele" 3 => "R. Firth" 4 => "F. Dong" 5 => "R. Owen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1185/03007990802675096" "Revista" => array:6 [ "tituloSerie" => "Curr Med Res Opin" "fecha" => "2009" "volumen" => "25" "paginaInicial" => "463" "paginaFinal" => "470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19192991" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of indacaterol, a novel long-acting _2-agonist, on isola-ted human bronchi" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Naline" 1 => "A. Trifilieff" 2 => "R.A. Fairhurst" 3 => "C. Advenier" 4 => "M. Molimard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00032806" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2007" "volumen" => "29" "paginaInicial" => "575" "paginaFinal" => "581" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17135231" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacologi- cal characterisation of indacaterol a novel once daily inhaled _2 adrenoceptor agonist, on small airways in human and rat precision cut lung slices" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.G. Sturton" 1 => "A. Trifilieff" 2 => "A.G. Nicholson" 3 => "P.J. Barnes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JPET" "fecha" => "2008" "volumen" => "324" "paginaInicial" => "270" "paginaFinal" => "275" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Onset of action of indacaterol in patients with COPD: comparison with salbutamol and salmeterol- fluticasone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. Balint" 1 => "H. Watz" 2 => "C. Amos" 3 => "R. Owen" 4 => "M. Higgins" 5 => "B. Kramer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Chronic Obst Pulm Dis" "fecha" => "2010" "volumen" => "5" "paginaInicial" => "311" "paginaFinal" => "318" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of a new once-daily long-acting inhaled _2-agonist indacaterol versus twice-daily formoterol in COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Dahl" 1 => "K.F. Chung" 2 => "R. Buhl" 3 => "H. Magnussen" 4 => "V. Nonikov" 5 => "D. Jack" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2009.125435" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2010 Jun" "volumen" => "65" "paginaInicial" => "473" "paginaFinal" => "479" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20522841" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of indacaterol 150 _g once-daily in COPD: a double-blind, randomized, 12-week study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Feldman" 1 => "T. Siler" 2 => "N. Prasad" 3 => "D. Jack" 4 => "S. Piggott" 5 => "R. Owen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2466-10-11" "Revista" => array:5 [ "tituloSerie" => "BMC Pulm Med" "fecha" => "2010" "volumen" => "10" "paginaInicial" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20211002" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Once-daily indacaterol vs twice-daily salmeterol for COPD: a placebo-controlled comparison" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. Kornmann" 1 => "R. Dahl" 2 => "S. Centanni" 3 => "A. Dogra" 4 => "R. Owen" 5 => "C. Lassen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Eur Respir J Epub" "fecha" => "2010 Aug 6" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and tolerability of indacaterol once-daily in COPD patients versus placebo and tiotropium: a 26-week study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Worth" 1 => "E. Kleerup" 2 => "A. Iqbal" 3 => "R. Owen" 4 => "B. Kramer" 5 => "M. Higgins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "ERS" "fecha" => "2009" "paginaInicial" => "P2030" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics of a capsule based dry pow-der inhaler for the delivery of indacaterol" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Pavkov" 1 => "S. Mueller" 2 => "K. Fiebich" 3 => "D. Singh" 4 => "F. Stowasser" 5 => "G. Pignatelli" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Curr Med Res Op" "fecha" => "2010" "volumen" => "26" "paginaInicial" => "2527" "paginaFinal" => "2533" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dose delivery characterization of indacaterol fol-lowing inhalation by COPD patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Singh" 1 => "K. Fiebich" 2 => "J. Dederichs" 3 => "R. Pavkov" 4 => "M. Schulte" 5 => "K. Sommerer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Poster presented at ATS, Novartis Pharma database" "fecha" => "2011" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pati- ent handling and preference for the single-dose dry-powder inhalers used witn indacaterol and tiotropium" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.R. Chapman" 1 => "C.M. Fogarty" 2 => "C. Peckitt" 3 => "C. Lassen" 4 => "B. Kramer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Poster presen-ted at ATS, Novartis Pharma database" "fecha" => "2011" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735115/0000001800000001/v1_201305151555/S2173511511000868/v1_201305151555/en/main.assets" "Apartado" => array:4 [ "identificador" => "9716" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorials" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735115/0000001800000001/v1_201305151555/S2173511511000868/v1_201305151555/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511511000868?idApp=UINPBA00004E" ]
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