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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The indications &#40;and contraindications&#41; of treatment with inhaled corticosteroids &#40;ICS&#41; in patients with chronic obstructive pulmonary disease &#40;COPD&#41; are well established in the latest iteration of the Global Strategy for the Diagnosis&#44; Management and Prevention of COPD &#40;GOLD&#41; document&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> According to this document&#44; ICS are <span class="elsevierStyleItalic">indicated</span> in COPD patients with severe or very severe airflow limitation &#40;FEV1<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&#37; of predicted&#41; and&#47;or frequent exacerbations &#40;ECOPD&#41; that are not adequately controlled by long-acting bronchodilators &#40;Evidence A&#41; because they reduce the risk of future episodes of ECOPD&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> More recently&#44; ICS have also been recommended for the treatment of the so-called Asthma-COPD overlap syndrome &#40;ACOS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> On the contrary&#44; ICS <span class="elsevierStyleItalic">should never be used</span> in mono-therapy &#40;i&#46;e&#46;&#44; alone&#41; in COPD patients<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> &#40;an important difference vs&#46; asthma<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a>&#41;&#46; Despite this&#44; apparently straightforward situation&#44; there is a lively debate on where ICS should be positioned in the treatment of COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> This Editorial briefly discusses what&#44; in my opinion&#44; are some of the main arguments that fuel this debate&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">First&#44; drug therapy in COPD was actually &#8220;inherited&#8221; from asthma and basically consisted in the use of long-acting &#946;2 agonists &#40;LABA&#41; and ICS&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> It is only recently that new long-acting bronchodilators have been developed specifically for the treatment of COPD &#40;not asthma&#41;&#44; as best exemplified by tiotropium &#40;a long acting anti-muscarininc agent&#59; LAMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> Even more recently&#44; new fixed combination of LABA-LAMA&#39;s have been also developed for COPD and can now be prescribed in many markets&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#44;8</span></a> To my mind&#44; the availability of these new therapeutic alternatives will inevitably force the academic community to carefully re-consider the position ICS within the therapeutic armamentarium of COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> For instance&#44; the recent ILLUMINATE study<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> showed&#44; not surprisingly&#44; that lung function improvement was significantly better in patients who received a fixed combination of indacaterol &#40;LABA&#41; and glycopirronium &#40;LAMA&#41; than in those who received a fixed combination of salmeterol &#40;LABA&#41; and fluticasone propionate &#40;ICS&#41;&#58; two bronchodilators bronchodilate more than one&#33;&#46; Interestingly&#44; authors did not find significant differences in the incidence of &#8220;adverse events&#8221; &#40;including ECOPD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> This observation may indicate that a LABA-LAMA combination has a similar effect on ECOPD than a LABA-ICS combination and&#44; remember&#44; according to GOLD&#44; ICS are indicated in COPD to reduce the risk of future exacerbations&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Yet&#44; as it is often the case&#44; the devil is in the details since&#58; &#40;1&#41; this study lasted for 26 weeks only&#44; probably a period of time that is too short to assess with certainty the effect of any treatment on the incidence of ECOPD&#59; &#40;2&#41; the study included patients <span class="elsevierStyleItalic">without</span> a history of previous ECOPD&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> when it is well established that the best predictor of future ECOPD is a previous history of ECOPD<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a>&#59; and&#44; &#40;3&#41; patients who had a moderate-to-severe ECOPD were withdrawn from the study&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Second&#44; likely as a consequence of ICS being &#8220;inherited&#8221; from asthma&#44; as discussed above&#44; there is ICS over prescription in COPD&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> particularly in patients classified in GOLD groups A or B&#44; where ICS should not be theoretically prescribed&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Not surprisingly&#44; therefore&#44; there has been interest in studying the effect of ICS withdrawal in COPD&#46; In this context&#44; the WISDOM study published recently<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> concludes that in patients with severe COPD receiving tiotropium &#40;LAMA&#41; plus salmeterol &#40;LABA&#41; plus fluticasone propionate &#40;ICS&#41;&#44; the gradual discontinuation of the latter until complete suppression does not increase significantly the risk of moderate or severe ECOPD&#44; albeit there was a significantly greater decline in lung function in those patients in whom ICS was withdrawn&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> However&#44; the devil is in the details again since&#58; &#40;1&#41; an inclusion criterion in the WISDOM study was that patients must have had one or more ECOPD in the preceding year&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Given that 70&#37; of the patients finally included in the study were already on ICS treatment during this period &#40;plus LABA&#44; LAMA or both&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> this criteria implies <span class="elsevierStyleItalic">de facto</span> that patients who&#44; while on ICS&#44; had not had previous ECOPD were <span class="elsevierStyleItalic">excluded</span> from the study&#46; In other words&#44; the study excluded those patients who&#44; theoretically&#44; could benefit most from ICS and included those who&#44; apparently&#44; were not well controlled while on ICS&#46; There should be no surprise then that ICS discontinuation in the latter did not have any major effect&#59; and&#44; &#40;2&#41; as acknowledged by the authors&#44; there was a significant difference &#40;43<span class="elsevierStyleHsp" style=""></span>ml in 10 months&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; in the rate of FEV1 decline in favor of those patients who continued on ICS&#46; Authors considered that this difference was not clinically relevant&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Personally I have to disagree with this interpretation&#44; since the FEV1 of these patients at entry in the study was 900<span class="elsevierStyleHsp" style=""></span>ml only&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> On the contrary&#44; I believe that this indeed indicates that ICS treatment can contribute to reducing the excessive decline of lung function in COPD&#44; as suggested by some previous reports&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;12</span></a> In fact&#44; other previous studies had also shown already that ICS withdrawal leads indeed to enhanced FEV1 decline&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">13&#44;14&#44;22</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Third&#44; and finally&#44; treatment with ICS has been linked to an increased risk of pneumonia in COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> This also questions the positioning of ICS in the treatment of COPD&#46; However&#44; these are peculiar &#8220;pneumonias&#8221;&#44; since they do not increase the risk of mortality and&#44; in some studies&#44; they may even reduce it&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> Further&#44; a forgotten element in this debate is the optimal ICS dose to be used in COPD&#46; Given that the dose-response curve of ICS is relatively flat &#40;at least in terms of lung function changes&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> it is possible that lower doses of ICS may have a more favorable efficacy&#47;risk ratio in COPD&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In summary&#44; despite the apparently straightforward recommendations of GOLD in relation to the positioning of ICS in the treatment of COPD discussed at the beginning of this Editorial&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> certainly there are reasons for the debate&#46; It is only through rigorous research that we will be able to answer these questions and to select those COPD patients who may benefit most from the use of ICS&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#44;18</span></a> Having said that&#44; however&#44; it is also important to note that the framework of this debate can change radically if future research shows that ICS may have effects that go beyond ECOPD and&#47;or lung function decline&#44; including the chemoprevention of lung cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> one of the most frequent causes of death in COPD&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a> and&#47;or the reduction of cardiovascular risk&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> another very common cause of morbidity and mortality in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a> Stay tuned&#58; the debate continues&#33;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">I have received grant support and&#47;or fees for speaking at conferences and&#47;or participating in advisory boards related to COPD management from Almirall&#44; AstraZeneca&#44; Boheringer-Ingelheim&#44; Chiesi&#44; GSK&#44; Kyorin&#44; Menarini&#44; MSD&#44; Novartis&#44; Takeda and TEVA&#46;</p></span></span>"
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                            3 => "G&#46;T&#46; Ferguson"
                            4 => "C&#46; Jenkins"
                            5 => "P&#46;W&#46; Jones"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2007"
                        "volumen" => "356"
                        "paginaInicial" => "775"
                        "paginaFinal" => "789"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17314337"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A 4-year trial of tiotropium in chronic obstructive pulmonary disease"
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                            0 => "D&#46;P&#46; Tashkin"
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                            2 => "S&#46; Senn"
                            3 => "D&#46; Burkhart"
                            4 => "S&#46; Kesten"
                            5 => "S&#46; Menjoge"
                          ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2008"
                        "volumen" => "359"
                        "paginaInicial" => "1543"
                        "paginaFinal" => "1554"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18836213"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease &#40;ILLUMINATE&#41;&#58; a randomised&#44; double-blind&#44; parallel group study"
                      "autores" => array:1 [
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                            1 => "E&#46;D&#46; Bateman"
                            2 => "J&#46; pallante"
                            3 => "V&#46;K&#46; Alagappan"
                            4 => "P&#46; D&#8217;Andrea"
                            5 => "H&#46; Chen"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(12)70052-8"
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                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2013"
                        "volumen" => "1"
                        "paginaInicial" => "51"
                        "paginaFinal" => "60"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24321804"
                            "web" => "Medline"
                          ]
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                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Efficacy and safety of umeclidinium plus vilanterol versus tiotropium&#44; vilanterol&#44; or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease&#58; results from two multicentre&#44; blinded&#44; randomised controlled trials"
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                            1 => "A&#46; Anzueto"
                            2 => "E&#46; Kerwin"
                            3 => "T&#46; Kaelin"
                            4 => "N&#46; Richard"
                            5 => "G&#46; Crater"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(14)70065-7"
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                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2014"
                        "volumen" => "2"
                        "paginaInicial" => "472"
                        "paginaFinal" => "486"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24835833"
                            "web" => "Medline"
                          ]
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                  ]
                ]
              ]
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              "identificador" => "bib0150"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Susceptibility to exacerbation in chronic obstructive pulmonary disease"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Hurst"
                            1 => "J&#46; Vestbo"
                            2 => "A&#46; Anzueto"
                            3 => "N&#46; Locantore"
                            4 => "H&#46; Mullerova"
                            5 => "R&#46; Tal-Singer"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0909883"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "1128"
                        "paginaFinal" => "1138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20843247"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
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              "identificador" => "bib0155"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation&#58; WISDOM study design and rationale"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "H&#46; Watz"
                            2 => "A&#46; Kirsten"
                            3 => "M&#46; Decramer"
                            4 => "R&#46; Dahl"
                            5 => "P&#46;M&#46; Calverley"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2014.01.002"
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                        "tituloSerie" => "Respir Med"
                        "fecha" => "2014"
                        "volumen" => "108"
                        "paginaInicial" => "593"
                        "paginaFinal" => "599"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24477080"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease&#58; results from the TORCH study"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            5 => "P&#46;W&#46; Jones"
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                    0 => array:2 [
                      "doi" => "10.1164/rccm.200712-1869OC"
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2008"
                        "volumen" => "178"
                        "paginaInicial" => "332"
                        "paginaFinal" => "338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18511702"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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              "identificador" => "bib0165"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease&#58; a randomized trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "J&#46;B&#46; Snoeck-Stroband"
                            2 => "M&#46;M&#46; Gosman"
                            3 => "D&#46;F&#46; Jansen"
                            4 => "S&#46;A&#46; Van"
                            5 => "H&#46;A&#46; Thiadens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2009"
                        "volumen" => "151"
                        "paginaInicial" => "517"
                        "paginaFinal" => "527"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19841453"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
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              "identificador" => "bib0170"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease&#58; the COPE study"
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                          "etal" => false
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                            0 => "P&#46; van der Valk"
                            1 => "E&#46; Monninkhof"
                            2 => "J&#46; Van der Palen"
                            3 => "G&#46; Zielhuis"
                            4 => "H&#46;C&#46; van"
                          ]
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200206-512OC"
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "166"
                        "paginaInicial" => "1358"
                        "paginaFinal" => "1363"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12406823"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0175"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Withdrawal of fluticasone propionate from combined salmeterol&#47;fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration&#58; a randomised controlled trial"
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                    0 => array:2 [
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                        "tituloSerie" => "Thorax"
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                        "volumen" => "60"
                        "paginaInicial" => "480"
                        "paginaFinal" => "487"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15923248"
                            "web" => "Medline"
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                        ]
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                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0180"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination&#58; TORCH study results"
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                          "etal" => true
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                            3 => "B&#46; Celli"
                            4 => "G&#46;T&#46; Ferguson"
                            5 => "C&#46; Jenkins"
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                    0 => array:2 [
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                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2009"
                        "volumen" => "34"
                        "paginaInicial" => "641"
                        "paginaFinal" => "647"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19443528"
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                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Incident pneumonia and mortality in patients with chronic obstructive pulmonary disease&#46; A double effect of inhaled corticosteroids&#63;"
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2014"
                        "volumen" => "191"
                        "paginaInicial" => "141"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25409118"
                            "web" => "Medline"
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                    ]
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              ]
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              "identificador" => "bib0190"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD&#58; two replicate double-blind&#44; parallel-group&#44; randomised controlled trials"
                      "autores" => array:1 [
                        0 => array:2 [
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                            5 => "J&#46; Vestbo"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet Respir Med"
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                        "volumen" => "1"
                        "paginaInicial" => "201"
                        "paginaFinal" => "223"
                      ]
                    ]
                  ]
                ]
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              "identificador" => "bib0195"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blood eosinophil guided prednisolone therapy for exacerbations of COPD&#58; a further analysis"
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                        0 => array:2 [
                          "etal" => false
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                            4 => "C&#46;E&#46; Brightling"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00062614"
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                        "tituloSerie" => "Eur Respir J"
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                        "volumen" => "44"
                        "paginaInicial" => "789"
                        "paginaFinal" => "791"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24925917"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
                  ]
                ]
              ]
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            18 => array:3 [
              "identificador" => "bib0200"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled corticosteroids and lung cancer chemoprevention in chronic obstructive pulmonary disease patients&#58; what should we make of what we observe&#63;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Ann Respir Med"
                        "fecha" => "2010"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality in COPD&#58; role of comorbidities"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;D&#46; Sin"
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                            2 => "J&#46;B&#46; Soriano"
                            3 => "A&#46;G&#46; Agusti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00133805"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2006"
                        "volumen" => "28"
                        "paginaInicial" => "1245"
                        "paginaFinal" => "1257"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17138679"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Study to Understand Mortality and Morbidity in COPD &#40;SUMMIT&#41; study protocol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "J&#46; Anderson"
                            2 => "R&#46;D&#46; Brook"
                            3 => "P&#46;M&#46;A&#46; Calverley"
                            4 => "B&#46;R&#46; Celli"
                            5 => "C&#46; Crim"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00087312"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2013"
                        "volumen" => "41"
                        "paginaInicial" => "1017"
                        "paginaFinal" => "1022"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23018908"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relapse in FEV1-decline after steroid withdrawal in chronic obstructive pulmonary disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46;I&#46; Kunz"
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                            2 => "K&#46; Klooster"
                            3 => "T&#46;S&#46; Lapperre"
                            4 => "J&#46;M&#46; Vonk"
                            5 => "J&#46;K&#46; Sont"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.14-3091"
                      "Revista" => array:3 [
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Editorial
Inhaled steroids in COPD: Reasons for a debate
Alvar Agustía,b
a Pulmonary Service, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
b Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The indications &#40;and contraindications&#41; of treatment with inhaled corticosteroids &#40;ICS&#41; in patients with chronic obstructive pulmonary disease &#40;COPD&#41; are well established in the latest iteration of the Global Strategy for the Diagnosis&#44; Management and Prevention of COPD &#40;GOLD&#41; document&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> According to this document&#44; ICS are <span class="elsevierStyleItalic">indicated</span> in COPD patients with severe or very severe airflow limitation &#40;FEV1<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&#37; of predicted&#41; and&#47;or frequent exacerbations &#40;ECOPD&#41; that are not adequately controlled by long-acting bronchodilators &#40;Evidence A&#41; because they reduce the risk of future episodes of ECOPD&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> More recently&#44; ICS have also been recommended for the treatment of the so-called Asthma-COPD overlap syndrome &#40;ACOS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> On the contrary&#44; ICS <span class="elsevierStyleItalic">should never be used</span> in mono-therapy &#40;i&#46;e&#46;&#44; alone&#41; in COPD patients<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> &#40;an important difference vs&#46; asthma<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a>&#41;&#46; Despite this&#44; apparently straightforward situation&#44; there is a lively debate on where ICS should be positioned in the treatment of COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> This Editorial briefly discusses what&#44; in my opinion&#44; are some of the main arguments that fuel this debate&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">First&#44; drug therapy in COPD was actually &#8220;inherited&#8221; from asthma and basically consisted in the use of long-acting &#946;2 agonists &#40;LABA&#41; and ICS&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> It is only recently that new long-acting bronchodilators have been developed specifically for the treatment of COPD &#40;not asthma&#41;&#44; as best exemplified by tiotropium &#40;a long acting anti-muscarininc agent&#59; LAMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> Even more recently&#44; new fixed combination of LABA-LAMA&#39;s have been also developed for COPD and can now be prescribed in many markets&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#44;8</span></a> To my mind&#44; the availability of these new therapeutic alternatives will inevitably force the academic community to carefully re-consider the position ICS within the therapeutic armamentarium of COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> For instance&#44; the recent ILLUMINATE study<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> showed&#44; not surprisingly&#44; that lung function improvement was significantly better in patients who received a fixed combination of indacaterol &#40;LABA&#41; and glycopirronium &#40;LAMA&#41; than in those who received a fixed combination of salmeterol &#40;LABA&#41; and fluticasone propionate &#40;ICS&#41;&#58; two bronchodilators bronchodilate more than one&#33;&#46; Interestingly&#44; authors did not find significant differences in the incidence of &#8220;adverse events&#8221; &#40;including ECOPD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> This observation may indicate that a LABA-LAMA combination has a similar effect on ECOPD than a LABA-ICS combination and&#44; remember&#44; according to GOLD&#44; ICS are indicated in COPD to reduce the risk of future exacerbations&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Yet&#44; as it is often the case&#44; the devil is in the details since&#58; &#40;1&#41; this study lasted for 26 weeks only&#44; probably a period of time that is too short to assess with certainty the effect of any treatment on the incidence of ECOPD&#59; &#40;2&#41; the study included patients <span class="elsevierStyleItalic">without</span> a history of previous ECOPD&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> when it is well established that the best predictor of future ECOPD is a previous history of ECOPD<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a>&#59; and&#44; &#40;3&#41; patients who had a moderate-to-severe ECOPD were withdrawn from the study&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Second&#44; likely as a consequence of ICS being &#8220;inherited&#8221; from asthma&#44; as discussed above&#44; there is ICS over prescription in COPD&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> particularly in patients classified in GOLD groups A or B&#44; where ICS should not be theoretically prescribed&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Not surprisingly&#44; therefore&#44; there has been interest in studying the effect of ICS withdrawal in COPD&#46; In this context&#44; the WISDOM study published recently<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> concludes that in patients with severe COPD receiving tiotropium &#40;LAMA&#41; plus salmeterol &#40;LABA&#41; plus fluticasone propionate &#40;ICS&#41;&#44; the gradual discontinuation of the latter until complete suppression does not increase significantly the risk of moderate or severe ECOPD&#44; albeit there was a significantly greater decline in lung function in those patients in whom ICS was withdrawn&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> However&#44; the devil is in the details again since&#58; &#40;1&#41; an inclusion criterion in the WISDOM study was that patients must have had one or more ECOPD in the preceding year&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Given that 70&#37; of the patients finally included in the study were already on ICS treatment during this period &#40;plus LABA&#44; LAMA or both&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> this criteria implies <span class="elsevierStyleItalic">de facto</span> that patients who&#44; while on ICS&#44; had not had previous ECOPD were <span class="elsevierStyleItalic">excluded</span> from the study&#46; In other words&#44; the study excluded those patients who&#44; theoretically&#44; could benefit most from ICS and included those who&#44; apparently&#44; were not well controlled while on ICS&#46; There should be no surprise then that ICS discontinuation in the latter did not have any major effect&#59; and&#44; &#40;2&#41; as acknowledged by the authors&#44; there was a significant difference &#40;43<span class="elsevierStyleHsp" style=""></span>ml in 10 months&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; in the rate of FEV1 decline in favor of those patients who continued on ICS&#46; Authors considered that this difference was not clinically relevant&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Personally I have to disagree with this interpretation&#44; since the FEV1 of these patients at entry in the study was 900<span class="elsevierStyleHsp" style=""></span>ml only&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> On the contrary&#44; I believe that this indeed indicates that ICS treatment can contribute to reducing the excessive decline of lung function in COPD&#44; as suggested by some previous reports&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;12</span></a> In fact&#44; other previous studies had also shown already that ICS withdrawal leads indeed to enhanced FEV1 decline&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">13&#44;14&#44;22</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Third&#44; and finally&#44; treatment with ICS has been linked to an increased risk of pneumonia in COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> This also questions the positioning of ICS in the treatment of COPD&#46; However&#44; these are peculiar &#8220;pneumonias&#8221;&#44; since they do not increase the risk of mortality and&#44; in some studies&#44; they may even reduce it&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> Further&#44; a forgotten element in this debate is the optimal ICS dose to be used in COPD&#46; Given that the dose-response curve of ICS is relatively flat &#40;at least in terms of lung function changes&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> it is possible that lower doses of ICS may have a more favorable efficacy&#47;risk ratio in COPD&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In summary&#44; despite the apparently straightforward recommendations of GOLD in relation to the positioning of ICS in the treatment of COPD discussed at the beginning of this Editorial&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> certainly there are reasons for the debate&#46; It is only through rigorous research that we will be able to answer these questions and to select those COPD patients who may benefit most from the use of ICS&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#44;18</span></a> Having said that&#44; however&#44; it is also important to note that the framework of this debate can change radically if future research shows that ICS may have effects that go beyond ECOPD and&#47;or lung function decline&#44; including the chemoprevention of lung cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> one of the most frequent causes of death in COPD&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a> and&#47;or the reduction of cardiovascular risk&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> another very common cause of morbidity and mortality in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a> Stay tuned&#58; the debate continues&#33;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">I have received grant support and&#47;or fees for speaking at conferences and&#47;or participating in advisory boards related to COPD management from Almirall&#44; AstraZeneca&#44; Boheringer-Ingelheim&#44; Chiesi&#44; GSK&#44; Kyorin&#44; Menarini&#44; MSD&#44; Novartis&#44; Takeda and TEVA&#46;</p></span></span>"
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                            5 => "M&#46; FitzGerald"
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                        "paginaFinal" => "178"
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            3 => array:3 [
              "identificador" => "bib0125"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled steroids in COPD&#58; when should they be used&#63;"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Agusti"
                            1 => "L&#46;M&#46; Fabbri"
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                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(14)70227-9"
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                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2014"
                        "volumen" => "2"
                        "paginaInicial" => "869"
                        "paginaFinal" => "871"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25439566"
                            "web" => "Medline"
                          ]
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                ]
              ]
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              "identificador" => "bib0130"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;M&#46;A&#46; Calverley"
                            1 => "J&#46;A&#46; Anderson"
                            2 => "B&#46; Celli"
                            3 => "G&#46;T&#46; Ferguson"
                            4 => "C&#46; Jenkins"
                            5 => "P&#46;W&#46; Jones"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa063070"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2007"
                        "volumen" => "356"
                        "paginaInicial" => "775"
                        "paginaFinal" => "789"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17314337"
                            "web" => "Medline"
                          ]
                        ]
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                ]
              ]
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              "identificador" => "bib0135"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A 4-year trial of tiotropium in chronic obstructive pulmonary disease"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;P&#46; Tashkin"
                            1 => "B&#46; Celli"
                            2 => "S&#46; Senn"
                            3 => "D&#46; Burkhart"
                            4 => "S&#46; Kesten"
                            5 => "S&#46; Menjoge"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0805800"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2008"
                        "volumen" => "359"
                        "paginaInicial" => "1543"
                        "paginaFinal" => "1554"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18836213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0140"
              "etiqueta" => "7"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease &#40;ILLUMINATE&#41;&#58; a randomised&#44; double-blind&#44; parallel group study"
                      "autores" => array:1 [
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                          "autores" => array:6 [
                            0 => "C&#46;F&#46; Vogelmeier"
                            1 => "E&#46;D&#46; Bateman"
                            2 => "J&#46; pallante"
                            3 => "V&#46;K&#46; Alagappan"
                            4 => "P&#46; D&#8217;Andrea"
                            5 => "H&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(12)70052-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2013"
                        "volumen" => "1"
                        "paginaInicial" => "51"
                        "paginaFinal" => "60"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24321804"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0145"
              "etiqueta" => "8"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of umeclidinium plus vilanterol versus tiotropium&#44; vilanterol&#44; or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease&#58; results from two multicentre&#44; blinded&#44; randomised controlled trials"
                      "autores" => array:1 [
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                          "autores" => array:6 [
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                            1 => "A&#46; Anzueto"
                            2 => "E&#46; Kerwin"
                            3 => "T&#46; Kaelin"
                            4 => "N&#46; Richard"
                            5 => "G&#46; Crater"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(14)70065-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2014"
                        "volumen" => "2"
                        "paginaInicial" => "472"
                        "paginaFinal" => "486"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24835833"
                            "web" => "Medline"
                          ]
                        ]
                      ]
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                  ]
                ]
              ]
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              "identificador" => "bib0150"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Susceptibility to exacerbation in chronic obstructive pulmonary disease"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Hurst"
                            1 => "J&#46; Vestbo"
                            2 => "A&#46; Anzueto"
                            3 => "N&#46; Locantore"
                            4 => "H&#46; Mullerova"
                            5 => "R&#46; Tal-Singer"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0909883"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "1128"
                        "paginaFinal" => "1138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20843247"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0155"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation&#58; WISDOM study design and rationale"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Magnussen"
                            1 => "H&#46; Watz"
                            2 => "A&#46; Kirsten"
                            3 => "M&#46; Decramer"
                            4 => "R&#46; Dahl"
                            5 => "P&#46;M&#46; Calverley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2014.01.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2014"
                        "volumen" => "108"
                        "paginaInicial" => "593"
                        "paginaFinal" => "599"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24477080"
                            "web" => "Medline"
                          ]
                        ]
                      ]
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                  ]
                ]
              ]
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              "identificador" => "bib0160"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease&#58; results from the TORCH study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "N&#46;E&#46; Thomas"
                            2 => "J&#46;A&#46; Anderson"
                            3 => "G&#46;T&#46; Ferguson"
                            4 => "C&#46;R&#46; Jenkins"
                            5 => "P&#46;W&#46; Jones"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200712-1869OC"
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2008"
                        "volumen" => "178"
                        "paginaInicial" => "332"
                        "paginaFinal" => "338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18511702"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease&#58; a randomized trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;S&#46; Lapperre"
                            1 => "J&#46;B&#46; Snoeck-Stroband"
                            2 => "M&#46;M&#46; Gosman"
                            3 => "D&#46;F&#46; Jansen"
                            4 => "S&#46;A&#46; Van"
                            5 => "H&#46;A&#46; Thiadens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2009"
                        "volumen" => "151"
                        "paginaInicial" => "517"
                        "paginaFinal" => "527"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19841453"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease&#58; the COPE study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; van der Valk"
                            1 => "E&#46; Monninkhof"
                            2 => "J&#46; Van der Palen"
                            3 => "G&#46; Zielhuis"
                            4 => "H&#46;C&#46; van"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200206-512OC"
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "166"
                        "paginaInicial" => "1358"
                        "paginaFinal" => "1363"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12406823"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0175"
              "etiqueta" => "14"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Withdrawal of fluticasone propionate from combined salmeterol&#47;fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration&#58; a randomised controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            3 => "W&#46;C&#46; Hop"
                            4 => "J&#46; Prins"
                            5 => "A&#46;F&#46; Kuipers"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Thorax"
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                        "volumen" => "60"
                        "paginaInicial" => "480"
                        "paginaFinal" => "487"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15923248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            14 => array:3 [
              "identificador" => "bib0180"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination&#58; TORCH study results"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "J&#46;A&#46; Anderson"
                            3 => "B&#46; Celli"
                            4 => "G&#46;T&#46; Ferguson"
                            5 => "C&#46; Jenkins"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00193908"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2009"
                        "volumen" => "34"
                        "paginaInicial" => "641"
                        "paginaFinal" => "647"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19443528"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0185"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incident pneumonia and mortality in patients with chronic obstructive pulmonary disease&#46; A double effect of inhaled corticosteroids&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201409-1654PP"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2014"
                        "volumen" => "191"
                        "paginaInicial" => "141"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25409118"
                            "web" => "Medline"
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                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0190"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD&#58; two replicate double-blind&#44; parallel-group&#44; randomised controlled trials"
                      "autores" => array:1 [
                        0 => array:2 [
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                            3 => "N&#46;A&#46; Hanania"
                            4 => "D&#46;A&#46; Mahler"
                            5 => "J&#46; Vestbo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet Respir Med"
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                        "volumen" => "1"
                        "paginaInicial" => "201"
                        "paginaFinal" => "223"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blood eosinophil guided prednisolone therapy for exacerbations of COPD&#58; a further analysis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "L&#46; Davies"
                            2 => "P&#46;M&#46;A&#46; Calverley"
                            3 => "S&#46;D&#46; Aaron"
                            4 => "C&#46;E&#46; Brightling"
                            5 => "I&#46;D&#46; Pavord"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00062614"
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                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2014"
                        "volumen" => "44"
                        "paginaInicial" => "789"
                        "paginaFinal" => "791"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24925917"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled corticosteroids and lung cancer chemoprevention in chronic obstructive pulmonary disease patients&#58; what should we make of what we observe&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "V&#46; Kiri"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Ann Respir Med"
                        "fecha" => "2010"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality in COPD&#58; role of comorbidities"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;D&#46; Sin"
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                            2 => "J&#46;B&#46; Soriano"
                            3 => "A&#46;G&#46; Agusti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00133805"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2006"
                        "volumen" => "28"
                        "paginaInicial" => "1245"
                        "paginaFinal" => "1257"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17138679"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Study to Understand Mortality and Morbidity in COPD &#40;SUMMIT&#41; study protocol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Vestbo"
                            1 => "J&#46; Anderson"
                            2 => "R&#46;D&#46; Brook"
                            3 => "P&#46;M&#46;A&#46; Calverley"
                            4 => "B&#46;R&#46; Celli"
                            5 => "C&#46; Crim"
                          ]
                        ]
                      ]
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Article information
ISSN: 21735115
Original language: English
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Pulmonology

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