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array:24 [ "pii" => "S1579212919304252" "issn" => "15792129" "doi" => "10.1016/j.arbr.2019.09.002" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "2299" "copyright" => "SEPAR" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2020;56:106-13" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0300289619303941" "issn" => "03002896" "doi" => "10.1016/j.arbres.2019.09.023" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "2299" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Arch Bronconeumol. 2020;56:106-13" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 239 "formatos" => array:2 [ "HTML" => 129 "PDF" => 110 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo Especial</span>" "titulo" => "Incorporando nuevas evidencias sobre medicamentos inhalados en la EPOC. Asociación Latinoamericana de Tórax (ALAT) 2019" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "106" "paginaFinal" => "113" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Incorporating New Evidence on Inhaled Medications in COPD. The Latin American Chest Association (ALAT) 2019" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1728 "Ancho" => 2543 "Tamanyo" => 282728 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Esquema del tratamiento inhalado según la gravedad de la EPOC. ALAT-2019.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Montes de Oca, Maria Victorina López Varela, Agustín Acuña, Eduardo Schiavi, Alejandro Casas, Antonio Tokumoto, Carlos A. Torres Duque, Alejandra Ramírez-Venegas, Gabriel García, Aquiles Camelier, Miguel Bergna, Mark Cohen, Efraín Sanchez-Angarita, Santiago Guzmán, Karen Czischke, Manuel Barros, Alejandra Rey" "autores" => array:17 [ 0 => array:2 [ "nombre" => "María" "apellidos" => "Montes de Oca" ] 1 => array:2 [ "nombre" => "Maria Victorina" "apellidos" => "López Varela" ] 2 => array:2 [ "nombre" => "Agustín" "apellidos" => "Acuña" ] 3 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Schiavi" ] 4 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Casas" ] 5 => array:2 [ "nombre" => "Antonio" "apellidos" => "Tokumoto" ] 6 => array:2 [ "nombre" => "Carlos A." "apellidos" => "Torres Duque" ] 7 => array:2 [ "nombre" => "Alejandra" "apellidos" => "Ramírez-Venegas" ] 8 => array:2 [ "nombre" => "Gabriel" "apellidos" => "García" ] 9 => array:2 [ "nombre" => "Aquiles" "apellidos" => "Camelier" ] 10 => array:2 [ "nombre" => "Miguel" "apellidos" => "Bergna" ] 11 => array:2 [ "nombre" => "Mark" "apellidos" => "Cohen" ] 12 => array:2 [ "nombre" => "Efraín" "apellidos" => "Sanchez-Angarita" ] 13 => array:2 [ "nombre" => "Santiago" "apellidos" => "Guzmán" ] 14 => array:2 [ "nombre" => "Karen" "apellidos" => "Czischke" ] 15 => array:2 [ "nombre" => "Manuel" "apellidos" => "Barros" ] 16 => array:2 [ "nombre" => "Alejandra" "apellidos" => "Rey" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1579212919304252" "doi" => "10.1016/j.arbr.2019.09.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212919304252?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289619303941?idApp=UINPBA00003Z" "url" => "/03002896/0000005600000002/v4_202007190708/S0300289619303941/v4_202007190708/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1579212919304136" "issn" => "15792129" "doi" => "10.1016/j.arbr.2019.12.001" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "2117" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2020;56:114" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Clinical Image</span>" "titulo" => "Azygos Lobe and Inferior Vena Cava Agenesis: A Rare Association of Two Uncommon Malformations" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "114" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lóbulo de la ácigos y agenesia de la vena cava inferior: una rara asociación de dos infrecuentes malformaciones" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 892 "Ancho" => 1255 "Tamanyo" => 161127 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Images A and B show the existence of an accessory fissure formed by a hypertrophic azygos. 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HRCT: high-resolution computed tomography; IPF: idiopathic pulmonary fibrosis; UIP: usual interstitial pneumonia.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Diego Castillo, Albert Sánchez-Font, Virginia Pajares, Tomás Franquet, Roger Llatjós, Irene Sansano, Jacobo Sellarés, Carmen Centeno, Juan J. 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"apellidos" => "Fibla" ] 9 => array:2 [ "nombre" => "Marcelo" "apellidos" => "Sánchez" ] 10 => array:2 [ "nombre" => "José" "apellidos" => "Ramírez" ] 11 => array:2 [ "nombre" => "Amalia" "apellidos" => "Moreno" ] 12 => array:2 [ "nombre" => "Juan Carlos" "apellidos" => "Trujillo-Reyes" ] 13 => array:2 [ "nombre" => "Enric" "apellidos" => "Barbeta" ] 14 => array:2 [ "nombre" => "María" "apellidos" => "Molina-Molina" ] 15 => array:2 [ "nombre" => "Alfons" "apellidos" => "Torrego" ] 16 => array:1 [ "colaborador" => "por el grupo de trabajo CRIOMPID" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289619303011" "doi" => "10.1016/j.arbres.2019.07.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289619303011?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212919304215?idApp=UINPBA00003Z" "url" => "/15792129/0000005600000002/v2_202002112050/S1579212919304215/v2_202002112050/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>" "titulo" => "Incorporating new evidence on inhaled medications in COPD. The latin American chest association (ALAT) 2019" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "106" "paginaFinal" => "113" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Maria Montes de Oca, Maria Victorina López Varela, Agustín Acuña, Eduardo Schiavi, Alejandro Casas, Antonio Tokumoto, Carlos A. Torres Duque, Alejandra Ramírez-Venegas, Gabriel García, Aquiles Camelier, Miguel Bergna, Mark Cohen, Efraín Sanchez-Angarita, Santiago Guzmán, Karen Czischke, Manuel Barros, Alejandra Rey" "autores" => array:17 [ 0 => array:4 [ "nombre" => "Maria" "apellidos" => "Montes de Oca" "email" => array:1 [ 0 => "montesdeoca.maria@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Maria Victorina López" "apellidos" => "Varela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Agustín" "apellidos" => "Acuña" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Schiavi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Alejandro" "apellidos" => "Casas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Antonio" "apellidos" => "Tokumoto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 6 => array:3 [ "nombre" => "Carlos A. Torres" "apellidos" => "Duque" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 7 => array:3 [ "nombre" => "Alejandra" "apellidos" => "Ramírez-Venegas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 8 => array:3 [ "nombre" => "Gabriel" "apellidos" => "García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 9 => array:3 [ "nombre" => "Aquiles" "apellidos" => "Camelier" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 10 => array:3 [ "nombre" => "Miguel" "apellidos" => "Bergna" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 11 => array:3 [ "nombre" => "Mark" "apellidos" => "Cohen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] 12 => array:3 [ "nombre" => "Efraín" "apellidos" => "Sanchez-Angarita" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 13 => array:3 [ "nombre" => "Santiago" "apellidos" => "Guzmán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 14 => array:3 [ "nombre" => "Karen" "apellidos" => "Czischke" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] ] ] 15 => array:3 [ "nombre" => "Manuel" "apellidos" => "Barros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] ] ] 16 => array:3 [ "nombre" => "Alejandra" "apellidos" => "Rey" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:14 [ 0 => array:3 [ "entidad" => "Hospital Universitario de Caracas, Universidad Central de Venezuela, Caracas, Venezuela" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidad de la República, Hospital Maciel, Montevideo, Uruguay" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Investigación y Estadística, ITSalud/Medsolid. Caracas, Venezuela" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "SubSecretaría de Planificación Sanitaria. Ministerio de Salud. Gobierno de la Ciudad Autónoma de Buenos Aires, Argentina" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Fundación Neumológica Colombiana, Bogotá, Colombia" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Hospital Central Fuerza Aérea del Perú, Lima, Peru" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, Mexico" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital Rodolfo Rossi, La Plata, Argentina" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Universidade do Estado da Bahia e Escola Bahiana de Medicina, Salvador, Brazil" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Hospital Dr. Antonio Cetrángolo, Vicente López, Buenos Aires, Argentina" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Hospital Centro Médico, Guatemala, Guatemala" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Hospital José Gregorio Hernández, Caracas, Venezuela" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Clínica Alemana de Santiago. Hospital Padre Hurtado. Universidad del Desarrollo, Chile" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Escuela de Medicina, Universidad de Valparaíso. Hospital C. Van Buren, Chile" "etiqueta" => "n" "identificador" => "aff0070" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Incorporando nuevas evidencias sobre medicamentos inhalados en la EPOC. Asociación Latinoamericana de Tórax (ALAT) 2019" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1724 "Ancho" => 2559 "Tamanyo" => 276783 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0105" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Inhaled treatment depending on the severity of COPD. ALAT-2019.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The different forms of obstructive pulmonary disease (COPD) require individualized treatment plans (precision medicine). Recent studies provide evidence of the benefits of different combinations of drugs that can impact on therapeutic regimens.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2014, the Latin American Chest Association (ALAT) published a document on COPD using clinical questions in PICO format.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In this document, we aim to update the information on inhaled medicines by analyzing the new evidence using the same methodology. We have focused on inhaled medications because these drugs form the basis of the pharmacological treatment of COPD. Major changes and controversies are emerging in this area, regardless of the availability of controlled clinical studies. This document is intended for clinicians, particularly respiratory specialists and other professionals involved in the care and management of patients with COPD.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Methodology</span><p id="par0015" class="elsevierStylePara elsevierViewall">Medical specialists were invited by the COPD section of ALAT to participate in the development of this document. The working group discussed controversies in inhaled medications in COPD in 3 in-person meetings and by teleconference. New clinical questions were formulated on areas of controversy in inhaled medication, and this evidence was incorporated in a proposal for the use of this therapy. The 5 clinical questions discussed in this document were selected by consensus.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A more extensive description of the methodology, covering the formulation of clinical questions in PICO format, search strategy, eligibility criteria, critical analysis, and formulation of recommendations, can be found in <a class="elsevierStyleCrossRef" href="#sec0170">Appendix B</a> supplementary material of this document and in a prior publication.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> describe the search strategies (Trip Database and MeSH terms), and number and type of selected studies.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Using a cutoff date of September 2018, we rated publications in Spanish, Portuguese, and English according to the ACCP grading system, and classified the recommendation as strong or weak, according to risk, benefit, and burden ratios, and occasionally, cost. The quality of evidence was classed as high, moderate, or low, depending on the design of the study, consistency of results, and clarity of the evidence to answer the clinical question.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Bronchodilator monotherapy</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Question: are long-acting bronchodilators (LABA or LAMA) more effective than short-acting bronchodilators (SABA or SAMA) in patients with mild chronic obstructive pulmonary disease?</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Rationale</span><p id="par0030" class="elsevierStylePara elsevierViewall">Around 70 % of patients with COPD have mild-moderate airflow obstruction (FEV<span class="elsevierStyleInf">1</span> ≥ 50 %), with few respiratory symptoms.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–10</span></a> Information on inhaled medication in the initial stages or in mild disease is limited. Only 2 randomized controlled trials (RCT) in patients with mild-moderate obstruction have assessed the benefits of treatment with long-acting bronchodilators (BD) vs. placebo: one with tiotropium<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and another with the combination of long-acting ®<span class="elsevierStyleInf">2</span>-agonists<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>inhaled corticosteroids (LABA/ICS).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Tiotropium showed improvement in forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV<span class="elsevierStyleInf">1</span>), quality of life, frequency of exacerbations, and lung function decline.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In mild COPD, the use of any BD is usually recommended, so it would be interesting to analyze whether a long-acting BD instead of a short-acting BD is justified in these patients.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Search outcome</span><p id="par0035" class="elsevierStylePara elsevierViewall">A total of 485 references (MeSH: 465; Trip Database: 20) were retrieved, and 2 systematic reviews were selected to answer the question.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Quality of evidence</span><p id="par0040" class="elsevierStylePara elsevierViewall">In terms of efficacy, a systematic review comparing tiotropium vs. ipratropium (SAMA) in patients with moderate-severe obstruction shows greater benefit for tiotropium in lung function (increased FEV<span class="elsevierStyleInf">1</span>: 109<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 80−137<span class="elsevierStyleHsp" style=""></span>ml), quality of life (St. George's Respiratory Questionnaire [SGRQ] difference: −3.3; 95 % CI: 0.97–5.63), fewer hospitalizations (OR: 0.34; 95 % CI: 0.15-0.76) and exacerbations (OR: 0.71; 95 % CI: 0.52–0.95).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Another systematic review comparing ipratropium and LABAs<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> in patients with moderate-severe obstruction showed greater benefits for salmeterol in FEV<span class="elsevierStyleInf">1</span> (60<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 110−0<span class="elsevierStyleHsp" style=""></span>ml) and morning peak flow (−10.96 lit/min; 95 % CI: −16.09 to −5.83), with no difference in quality of life, exacerbations, rescue medication, exercise capacity, or symptoms. The use of formoterol compared with ipratropium seems to show improvement in morning peak flow with no difference in FEV<span class="elsevierStyleInf">1</span>, quality of life, dyspnea, or exercise capacity.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In terms of safety, the study that compared ipratropium vs. tiotropium reported fewer serious adverse events (OR: 0.50; 95 % CI: 0.34–0.73) and disease events with tiotropium (OR: 0.59; 95 % CI: 0.41–0.85), and no differences in mortality.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> No comparative studies of long-acting BD monotherapy vs. short-acting ®<span class="elsevierStyleInf">2</span>-agonists (SABA), or comparative studies between short-acting vs. long-acting BD in patients with mild obstruction were retrieved.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions and recommendations</span><p id="par0050" class="elsevierStylePara elsevierViewall">There is no available evidence that compares the use of short and long-acting BDs in COPD patients with mild obstruction. The comparative studies retrieved in the search and the evidence selected involves patients with moderate-severe obstruction. These show that, in terms of efficacy, tiotropium bromide<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LABA compared with ipratropium has greater benefits in lung function. Tiotropium also showed greater benefits in dyspnea, exacerbations, and quality of life, and a better safety profile.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The only recommendation that can be drawn from these findings is that LABA or tiotropium should be used in preference to ipratropium in COPD patients with moderate-severe obstruction in terms of dyspnea, quality of life, and lung function, and tiotropium bromide in preference to ipratropium in terms of improved exacerbation and hospitalization rates.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Combined therapies (LABA/ICS, LABA/LAMA and LABA/LAMA/ICS)</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Question: does the combination of LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICS provide greater benefits than monotherapy with LAMA or dual bronchodilator therapy with LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA?</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Rationale</span><p id="par0060" class="elsevierStylePara elsevierViewall">LAMA monotherapy offers benefits in dyspnea, quality of life, and frequency of exacerbations and hospitalizations.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–18</span></a> A reduction in exacerbations and improved quality of life and lung function have also been reported for LABA/ICS<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and LABA/LAMA.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,20–29</span></a> The question arises as to whether there are differences between these treatments.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Search outcome</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 238 references (MeSH: 230; Trip Database: 8) were retrieved, and 4 systematic reviews were selected to answer the question.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,32–34</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Quality of evidence</span><p id="par0070" class="elsevierStylePara elsevierViewall">In terms of efficacy, a systematic review comparing fluticasone/salmeterol vs. tiotropium in patients with moderate-severe obstruction shows similar results in exacerbation and hospitalization rates and quality of life.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> However, the number of drop-outs in one of the studies was high, the groups were poorly matched, and patients were not followed up after drop-out, which limits the applicability of its results.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Another systematic review in patients with moderate-severe obstruction showed modest improvement (without clinical relevance) with LABA/ICS (fluticasone/salmeterol) compared with tiotropium in pre-BD FEV<span class="elsevierStyleInf">1</span> (60<span class="elsevierStyleHsp" style=""></span>ml), rescue medication, and quality of life (SGRQ, −2.07 units).<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">A systematic review compared the effectiveness of LABA/LAMA with LABA/ICS (fluticasone/salmeterol) in patients with mostly moderate-severe COPD.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> LABA/LAMA showed greater benefits in lung function (trough FEV<span class="elsevierStyleInf">1</span> [MD 80<span class="elsevierStyleHsp" style=""></span>ml]) and risk of exacerbations (OR: 0.82). There was no difference in quality of life (SGRQ total score); however, the minimum clinical difference of 4 points was achieved more frequently with LABA/LAMA than with fluticasone/salmeterol (OR: 1.25).<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Another systematic review and meta-analysis in patients with moderate-very severe COPD showed greater benefits from LABA/LAMA in lung function (trough FEV<span class="elsevierStyleInf">1</span> [MD 80<span class="elsevierStyleHsp" style=""></span>ml]), risk of moderate-severe exacerbations (RR: 0.82), and use of rescue medication (-0.18 puffs/day) compared with LABA/ICS (fluticasone/salmeterol).<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> There was no difference between the therapies in quality of life or severity of dyspnea.</p><p id="par0090" class="elsevierStylePara elsevierViewall">With regard to safety, systematic reviews show an increased risk of pneumonia and serious adverse effects with fluticasone/salmeterol vs. tiotropium or LABA/LAMA.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions and recommendations</span><p id="par0095" class="elsevierStylePara elsevierViewall">The efficacy of tiotropium and fluticasone/salmeterol in patients with moderate-severe COPD is similar. LABA/LAMA has greater benefits in lung function and risk of exacerbations compared with fluticasone/salmeterol. With regard to safety, there is evidence of an increased risk of pneumonia with fluticasone/salmeterol vs. tiotropium bromide<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LABA/LAMA.</p><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">HIGH evidence</span> for the use of tiotropium or LABA/ICS (fluticasone/salmeterol) in terms of dyspnea, pulmonary function, quality of life, and frequency of exacerbations and hospitalizations in patients with moderate-severe COPD.</p><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">STRONG recommendation</span> to prefer tiotropium over fluticasone/salmeterol, due to an increased risk of pneumonia with the latter.</p><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">HIGH evidence and STRONG recommendation</span> for the use of LABA/LAMA in preference to LABA/ICS (fluticasone/salmeterol) to improve lung function and frequency of exacerbations, with less risk of pneumonia in patients with moderate-very severe COPD.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Question: does the combination of LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICS (triple therapy) provide greater benefits compared with LAMA monotherapy, combination therapy (LABA/ICS) or dual bronchodilator therapy (LABA/LAMA) in patients with COPD?</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Rationale</span><p id="par0115" class="elsevierStylePara elsevierViewall">The combination of LABA/LAMA/ICS may decrease the risk of exacerbations, hospitalizations, and healthcare costs in COPD patients with moderate-very severe obstruction.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35,36</span></a> Controversy persists on the efficacy and safety of fixed-dose combination triple therapy or combining different devices (LABA/ICS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>tiotropium or LABA/ICS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>glycopyrronium), compared with LAMA, LAMA/ICS or LABA/LAMA.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Search outcome</span><p id="par0120" class="elsevierStylePara elsevierViewall">A total of 193 references (MeSH: 181; Trip Database: 12), and 2 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37,38</span></a> and 5 RCTs<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4,39–41</span></a> were selected to answer the question.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Quality of evidence</span><p id="par0125" class="elsevierStylePara elsevierViewall">One systematic review showed greater benefits with triple therapy (LABA/ICS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>tiotropium) in hospitalizations for all causes (reduction of risk: 39 %; OR: 0.61; 95 % CI: 0.40–0.92), quality of life (SGRQ difference: −3.46; 95 % CI: −5.05 to −1.87), and lung function (pre-BD FEV<span class="elsevierStyleInf">1</span>: 60<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 40−80<span class="elsevierStyleHsp" style=""></span>ml at 3–6 months) compared with tiotropium in patients with moderate-severe COPD, with no differences in mortality or frequency of exacerbations.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Similar results were reported by another systematic review and meta-analysis.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Three RCTs in patients with FEV<span class="elsevierStyleInf">1</span> < 50 % and a history of exacerbations evaluated the efficacy and safety of a fixed-dose combination (beclomethasone dipropionate<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>formoterol fumarate<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>glycopyrronium [BDP/FF/GLY]) compared with tiotropium<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>; with BDP/FF<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>; and with indacaterol<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>glycopyrronium.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> BDP/FF/GLY compared with tiotropium showed greater benefits in the frequency of moderate-severe exacerbations (RR: 0.80; 95 % CI: 0.69 to −0.92), lung function (pre-BD FEV<span class="elsevierStyleInf">1</span> difference: 61<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 37−86<span class="elsevierStyleHsp" style=""></span>ml), quality of life (SGRQ responders: 1.33; 95 % CI: 1.10–1.59), and reduced use of rescue medication.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> The combination showed greater benefits compared with BDP/FF in lung function at 26 weeks (FEV<span class="elsevierStyleInf">1</span> pre-dose difference: 81<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 52−109<span class="elsevierStyleHsp" style=""></span>ml), a 23 % reduction in moderate-severe exacerbations (RR: 0.77; 95 % CI: 0.65-0.92), quality of life (responders) at 52 weeks (SGRQ, OR: 1.33; 95 % CI: 1.06–1.66), with no differences in dyspnea severity.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> BDP/FF/GLY compared to indacaterol/glycopyrronium showed greater benefits in the frequency of moderate-severe exacerbations (RR: 0.85; 95 % C: 0.72-0.99); there were no differences in lung function or quality of life.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Two RCTS compared a fixed-dose combination of fluticasone furoate/umeclidinium/vilanterol (FFL/UMEC/VI) with budesonide/formoterol (BUD/FF),<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> FFL/VI and UMEC/VI<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in symptomatic patients with moderate-severe obstruction and history of exacerbations. Compared to BUD/FF, the triple therapy showed greater benefits in lung function (trough FEV<span class="elsevierStyleInf">1</span>: difference 171<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 148–194, in favor of FFL/UMEC/VI), quality of life (SGRQ difference: −2.2; 95 % CI: −3.5 to −1, in favor of FFL/UMEC/VI), and the frequency of moderate-severe exacerbations (35 % reduction; 95 % CI: 14 %–51 %). A subanalysis<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> shows similar benefits with FFL/UMEC/VI over BUD/FF in symptomatic patients, regardless of the severity of COPD or prior treatment. One of the studies<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> showed greater benefits with FFL/UMEC/VI in the frequency of moderate-severe exacerbations, compared with FFL/VI (RR: 0.85; 95 % CI: 0.80 %–0.90 %, 15 % difference) and UMEC/VI (RR: 0.75; 95 % CI: 0.70–0.81, 25 % difference), regardless of the eosinophil count in blood, although there was a greater reduction of risk in patients with eosinophils > 150 cells/μl. This combination also showed greater benefits in lung function (FFL/UMEC/VI vs. FFL/VI<span class="elsevierStyleSmallCaps">,</span> trough FEV<span class="elsevierStyleInf">1</span> difference: 97<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 85−109<span class="elsevierStyleHsp" style=""></span>ml, and FFL/UMEC/VI vs. UMEC/VI<span class="elsevierStyleSmallCaps">,</span> trough FEV<span class="elsevierStyleInf">1</span> difference: 54<span class="elsevierStyleHsp" style=""></span>ml; 95 % CI: 39−69<span class="elsevierStyleHsp" style=""></span>ml) and quality of life (SGRQ, FFL/UMEC/VI vs. FFL/VI difference −1.8; 95 % CI: −2.4 to −1.1, and FFL/UMEC/VI vs. UMEC/VI −1.8; 95 % CI: −2.6 to −1.0). With regard to safety, triple therapy in different devices compared to tiotropium showed no differences in the appearance of adverse effects.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37,38</span></a> BDP/FF/GLY showed an incidence of pneumonia in a small group of patients (BDP/FF/GLY 2 % vs. tiotropium 1 %).<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> There were no differences in the incidence of pneumonia between BDP/FF/GLY and BDP/FF<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> or indacaterol/glycopyrronium<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>; however, the risk of a medical diagnosis of pneumonia with FFL/UMEC/VI was higher than with UMEC/VI (HR: 1.52; 95 % CI: 1.22–1.92).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions and recommendations</span><p id="par0135" class="elsevierStylePara elsevierViewall">In symptomatic COPD patients with severe-very severe obstruction and a history of exacerbations, triple therapy offers greater benefits in terms of efficacy, lung function, quality of life, and risk of exacerbations than tiotropium or LABA/ICS. Triple therapy compared with LABA/LAMA shows greater benefits in the risk of moderate-severe exacerbations. In comparison with FFL/VI or UMEC/VI, the FFL/UMEC/VI combination shows greater benefits in the frequency of moderate-severe exacerbations, regardless of eosinophil blood counts; although the benefit is greater in patients with > 150 cells/μl. The risk of pneumonia is greater in treatments containing ICS.</p><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">HIGH evidence and STRONG recommendation</span> for the use of triple therapy in symptomatic COPD patients with severe-very severe obstruction and risk of exacerbations to improve lung function and quality of life and decrease the risk of exacerbations.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Question: which COPD patients benefit from the use of ICS in the reduction of exacerbations?</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Rationale</span><p id="par0145" class="elsevierStylePara elsevierViewall">The use of ICS alone or in combination with LABA has shown benefits in COPD patients, including lower exacerbation rates and health status decline.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42,43</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">These outcomes should be analyzed in terms of the risk/benefit ratio, in particular the risk of pneumonia associated with ICS.</p><p id="par0155" class="elsevierStylePara elsevierViewall">A need is emerging to define the subgroup of patients with COPD who benefit most from ICS, focused on reducing the risk of exacerbation.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Search outcome</span><p id="par0160" class="elsevierStylePara elsevierViewall">A total of 338 references (MeSH: 246; Trip Database: 92), and 3 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33,44,45</span></a> and 2 RCTs<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,46</span></a> were selected to answer the question.</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Quality of evidence</span><p id="par0165" class="elsevierStylePara elsevierViewall">A systematic review comparing the efficacy of any dose or type of ICS with placebo in patients with moderate-severe COPD showed that ICS reduced the rate of exacerbations (-0.26 exacerbations per patient/year, 95 % CI: −0.37 to −0.14).<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Another systematic review comparing the effectiveness of LABA/ICS (mainly fluticasone/salmeterol) with ICS monotherapy in patients with mild-severe COPD showed a reduction in the frequency of exacerbation with LABA/ICS (RR: 0.91; 95 % CI: 0.85–0.97).<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Two RCTs with fluticasone/salmeterol included in this review showed that exacerbations requiring oral steroids were reduced with fluticasone/salmeterol, and another found no difference in the rate of hospitalization.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> A systematic review comparing the effectiveness of LABA/LAMA with LABA/ICS (fluticasone/salmeterol) in patients with mostly moderate-severe COPD showed greater benefits with LABA/LAMA in the risk of exacerbations (OR: 0.82; 95 % CI: 0.70–0.96). The studies included in the analysis were heterogeneous, and included an observation period of less than 1<span class="elsevierStyleHsp" style=""></span>year. Most included patients with moderate-severe COPD, with no recent exacerbations.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">An RCT that compared FFL/UMEC/VI with FFL/VI and UMEC/VI<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in patients with moderate-very severe obstruction and a history of exacerbations showed greater benefits with FFL/UMEC/VI in frequency of moderate-severe exacerbations, compared with FFL/VI (RR: 0.85; 95 % CI: 0.80 %–0.90 %, 15 % difference) and UMEC/VI (RR: 0.75; 95 % CI: 0.70–0.81, 25 % difference), regardless of the eosinophil count in blood, although there was a greater reduction of risk in patients with a eosinophil count > 150 cells/μl.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Another RCT evaluated the effect of intensifying LABA/ICS therapy (budesonide/formoterol) on the exacerbation rate in moderate-severe patients at the onset of upper respiratory tract infection.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> The incidence of exacerbations in the budesonide/formoterol and placebo groups was similar (14.6 vs. 16.2 %; HR: 0.77; 95 % CI: 0,46–1,33), although the risk of severe exacerbations was reduced by 72 % (HR: 0.28; 95 % CI: 0,11–0,74) with intensified therapy. A significantly reduced risk of exacerbation was observed in the subgroup of patients with more severe disease.</p><p id="par0180" class="elsevierStylePara elsevierViewall">In terms of safety, evidence suggests that treatments that include ICS are associated with more frequent serious adverse effects, in particular, an increased risk of pneumonia.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,33,44</span></a></p></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusions and recommendations</span><p id="par0185" class="elsevierStylePara elsevierViewall">In terms of efficacy, the use of long-term ICS shows a benefit in the risk of exacerbations in patients with moderate-severe COPD, which is greater in individuals with elevated eosinophils in blood. This benefit must be weighed up against the increased risk of pneumonia.</p><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Moderate evidence and strong recommendation</span> for the use of ICS in patients with moderate-severe COPD with a history of exacerbation and elevated eosinophils in blood, in terms of a reduced risk of exacerbations.</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Question: in which patients can ICS be safely withdrawn?</span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Rationale</span><p id="par0195" class="elsevierStylePara elsevierViewall">Overuse of ICS in COPD is a common practice,<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47–49</span></a> even though these medications are usually reserved for patients at high risk of exacerbations (one third of the total population).<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50,51</span></a> The long-term use of ICS is associated with an increased risk of adverse events, particularly pneumonia.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42,52</span></a> Patients who are unlikely to benefit and in whom discontinuation is safe must be identified.</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Search outcome</span><p id="par0200" class="elsevierStylePara elsevierViewall">A total of 588 references (MeSH: 247; Trip Database: 341) were retrieved, and 1 meta-analysis<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> and 2 RCTs<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">54,55</span></a> were selected to answer the question.</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Quality of evidence</span><p id="par0205" class="elsevierStylePara elsevierViewall">A meta-analysis that includes RCTs and real-world observational studies in patients with moderate-severe obstruction showed no increase in the overall risk of exacerbations after ICS withdrawal (OR: 1.03; 95 % CI: 0.95–1.12; p<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). However, the risk of moderate-severe exacerbation increased (2.4 % and 33.6 %, respectively), and the time to first exacerbation was shorter (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) in patients who discontinued ICS. ICS withdrawal was also associated with lung function decline (FEV<span class="elsevierStyleInf">1</span>: −30<span class="elsevierStyleHsp" style=""></span>ml) and reduced quality of life (+1,24 SGRQ units), without reaching a minimally significant clinical difference.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">An RCT evaluated the efficacy and safety of abrupt withdrawal of ICS from long-term triple therapy in COPD patients who were frequent exacerbators with FEV<span class="elsevierStyleInf">1</span> between 40 %–80 %.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> Patients were randomized to continue fluticasone/salmeterol<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>tiotropium or to switch to indacaterol/glycopyrronium. No differences were observed between groups in the frequency of moderate-severe exacerbations (0.52 vs. 0.48) (RR: 1.08; 95 % CI: 0.83–1.40) or the time to the first moderate-severe exacerbation (HR: 1.11; 95 % CI: 0.85–1.46).<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> The withdrawal of ICS was associated with a slight reduction in trough FEV<span class="elsevierStyleInf">1</span>: −26<span class="elsevierStyleHsp" style=""></span>ml (95 % CI: −53 to 1<span class="elsevierStyleHsp" style=""></span>ml).<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> Patients with a blood eosinophil count ≥ 300 cells/μl presented greater deterioration in lung function and an increased risk of exacerbation (RR: 1.86; 95 % CI: 1.06–3.29) Adverse events were similar between the groups.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> Another RCT assessed changes in airway inflammation after fluticasone was withdrawn in patients with moderate-severe COPD who received this medication long term.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> The interruption of fluticasone induced an increase in bronchial T cells, mast cells, and several types of cells in sputum (relapse in the production of inflammatory cells), which was accompanied by further lung function decline.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> The results suggest that airway inflammation is suppressed during treatment with fluticasone, but the nonsteroidal anti-inflammatory effects are not maintained after withdrawal.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conclusions and recommendations</span><p id="par0215" class="elsevierStylePara elsevierViewall">ICS can be withdrawn abruptly in COPD patients with a low risk of exacerbation, moderate-severe obstruction, and blood eosinophil count < 300 cells/μl without increasing the risk of exacerbation or affecting lung function. ICS should not be withdrawn in patients at high risk of exacerbation and moderate-severe obstruction, due to an increased risk of exacerbation and lung function decline.</p><p id="par0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Moderate evidence and strong recommendation</span> for withdrawal of ICS in COPD patients with a low risk of exacerbations, moderate-severe obstruction, and eosinophil blood count < 300 cells/μl.</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Incorporation of new evidence</span><p id="par0225" class="elsevierStylePara elsevierViewall">The treatment of COPD should be individualized according to disease severity and drug availability. General measures and prevention (education, smoking cessation, vaccination, and physical activity, among others), and pharmacological and non-pharmacological treatments should be taken into account.</p><p id="par0230" class="elsevierStylePara elsevierViewall">In view of all the evidence analyzed, we propose a scheme with progressive inhaled medication according to COPD severity (dyspnea, obstruction, or exacerbations) that can be modified according to clinical response (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">BD monotherapy is recommended in patients with mild disease (all criteria: dyspnea mMRC grade 1, FEV<span class="elsevierStyleInf">1</span> ≥ 80 % post-BD).</p><p id="par0240" class="elsevierStylePara elsevierViewall">The efficacy and safety of LAMA vs. LABA monotherapy were analyzed in an earlier study.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The evidence shows that in terms of efficacy, tiotropium and LABAs have similar benefits in dyspnea, lung function, and quality of life, but tiotropium is more effective in reducing the frequency of exacerbations. On the basis of the evidence analyzed, patients with moderate disease (with at least 1 parameter of severity: dyspnea mMRC grade 2, FEV<span class="elsevierStyleInf">1</span> 79 %−50 %, an exacerbation without hospitalization in the preceding year) should start bronchodilator monotherapy with LAMA or LABA, instead of LABA/ICS in view of the increased risk of pneumonia associated with ICS. LAMA/LABA can be escalated, according to response. The LABA/ICS combination is recommended in patients with asthma or a medical diagnosis of asthma before the age of 40 years (asthma−COPD overlap).<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Patients with severe disease (at least 1 severity parameter: mMRC dyspnea grade 3–4, FEV<span class="elsevierStyleInf">1</span> <50 %, ≥ 2 exacerbations in the last year, or ≥ 1 hospitalization for exacerbation) should start treatment with LAMA/LABA, except individuals with an eosinophil blood count ≥ 300 cells/μl, who should receive LABA/LAMA/ICS, given the benefits of triple therapy in the risk of exacerbations and lung function decline.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> Escalation to LABA/LAMA/ICS is indicated in patients who started LAMA/LABA, but who persist with exacerbations regardless of their eosinophil count.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> ICS withdrawal must be considered in certain circumstances: when the initial indication was incorrect or no response is elicited; in patients with side effects such as pneumonia; and in patients with a low risk of exacerbation and a serum eosinophil count of <300 cells/μl.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> The prophylactic use of azithromycin or roflumilast can be useful as additional therapy in reducing the number of exacerbations in severe patients.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">57,58</span></a></p></span></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conclusions</span><p id="par0250" class="elsevierStylePara elsevierViewall">This ALAT 2019 statement provides an overview of treatment with inhaled medication in chronic obstructive pulmonary disease (COPD), incorporating the evidence analyzed using PICO methodology, according to severity of the obstruction, symptoms, and risk of exacerbations.</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflict of interests</span><p id="par0255" class="elsevierStylePara elsevierViewall">Augustín Acuña and Ephraim Sanchez declare that they have received professional honoraria for the development and implementation of methodological aspects of this paper from ITSalud/Medsolid. All other authors declare no real or perceived conflict of interest.</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Funding</span><p id="par0260" class="elsevierStylePara elsevierViewall">This study was funded by <span class="elsevierStyleGrantSponsor" id="gs0005">AstraZeneca</span>, <span class="elsevierStyleGrantSponsor" id="gs0010">Boehringer Ingelheim</span>, and <span class="elsevierStyleGrantSponsor" id="gs0015">GlaxoSmithKline</span>. The sponsors did not play any part in the study and did not participate at any stage of the development of these guidelines. None of the authors was paid for their participation in the preparation of this update.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1304948" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1205118" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1304947" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1205119" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Methodology" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Bronchodilator monotherapy" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0015" "titulo" => "Question: are long-acting bronchodilators (LABA or LAMA) more effective than short-acting bronchodilators (SABA or SAMA) in patients with mild chronic obstructive pulmonary disease?" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Rationale" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Search outcome" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Quality of evidence" ] ] ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions and recommendations" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Combined therapies (LABA/ICS, LABA/LAMA and LABA/LAMA/ICS)" "secciones" => array:9 [ 0 => array:3 [ "identificador" => "sec0045" "titulo" => "Question: does the combination of LABA + ICS provide greater benefits than monotherapy with LAMA or dual bronchodilator therapy with LABA + LAMA?" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Rationale" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Search outcome" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Quality of evidence" ] ] ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions and recommendations" ] 2 => array:3 [ "identificador" => "sec0070" "titulo" => "Question: does the combination of LABA + LAMA + ICS (triple therapy) provide greater benefits compared with LAMA monotherapy, combination therapy (LABA/ICS) or dual bronchodilator therapy (LABA/LAMA) in patients with COPD?" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Rationale" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Search outcome" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Quality of evidence" ] ] ] 3 => array:2 [ "identificador" => "sec0090" "titulo" => "Conclusions and recommendations" ] 4 => array:3 [ "identificador" => "sec0095" "titulo" => "Question: which COPD patients benefit from the use of ICS in the reduction of exacerbations?" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Rationale" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Search outcome" ] 2 => array:2 [ "identificador" => "sec0110" "titulo" => "Quality of evidence" ] ] ] 5 => array:2 [ "identificador" => "sec0115" "titulo" => "Conclusions and recommendations" ] 6 => array:3 [ "identificador" => "sec0120" "titulo" => "Question: in which patients can ICS be safely withdrawn?" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0125" "titulo" => "Rationale" ] 1 => array:2 [ "identificador" => "sec0130" "titulo" => "Search outcome" ] 2 => array:2 [ "identificador" => "sec0135" "titulo" => "Quality of evidence" ] ] ] 7 => array:2 [ "identificador" => "sec0140" "titulo" => "Conclusions and recommendations" ] 8 => array:2 [ "identificador" => "sec0145" "titulo" => "Incorporation of new evidence" ] ] ] 7 => array:2 [ "identificador" => "sec0150" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0155" "titulo" => "Conflict of interests" ] 9 => array:2 [ "identificador" => "sec0160" "titulo" => "Funding" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-05-06" "fechaAceptado" => "2019-09-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1205118" "palabras" => array:3 [ 0 => "Chronic obstructive pulmonary disease" 1 => "COPD" 2 => "Inhaled medication." ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1205119" "palabras" => array:3 [ 0 => "Enfermedad pulmonar obstructiva crónica" 1 => "EPOC" 2 => "Medicación inhalada." ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">This document on COPD from the Latin American Chest Association (ALAT-2019) uses PICO methodology to analyze new evidence on inhaled medication and answer clinical questions. The following key points emerged from this analysis: 1) evidence is lacking on the comparison of short-acting vs. long-acting bronchodilators in patients with mild COPD; patients with moderate-to-severe COPD obtain greater benefit from long-acting bronchodilators; 2) the benefits of monotherapy with long-acting antimuscarinic agents (LAMA) and combined therapy with long-acting β<span class="elsevierStyleInf">2</span>-agonists and inhaled corticosteroids (LABA/ICS) are similar, although the latter is associated with a greater risk of pneumonia; 3) LABA/LAMA offer greater benefits in terms of lung function and risk of exacerbation than LABA/ICS (the latter involve an increased risk of pneumonia), 4) LAMA/LABA/ICS have greater therapeutic benefits than LABA/LAMA on the risk of moderate-severe exacerbations. With regard to the role of eosinophils in guiding the use of ICS, ICS withdrawal must be considered when the initial indication was wrong or no response is elicited, in patients with side effects such as pneumonia, and in patients with a low risk of exacerbation and an eosinophil blood count of < 300 cells/μl. All this evidence, categorized according to the severity of the obstruction, symptoms, and risk of exacerbations, has been used to generate an algorithm for the use of inhaled medication in COPD.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Este documento sobre EPOC de la Asociación Latinoamericana de Tórax (ALAT)-2019 analiza las nuevas evidencias de medicación inhalada utilizando la metodología de preguntas clínicas en formato PICO. Surgen de este análisis los siguientes puntos claves: 1) No hay evidencia que compare el uso de broncodilatadores de acción corta vs. larga en pacientes con EPOC leve; en aquellos con EPOC moderada-grave existe mayor beneficio de los broncodilatadores de acción larga, 2) beneficios similares de la monoterapia con antimuscarínicos de acción prolongada (LAMA) y la terapia combinada β<span class="elsevierStyleInf">2</span>-agonistas de acción larga/corticosteroides inhalados (LABA/CIS), asociada esta última a mayor riesgo de neumonía 3) mayores beneficios del LABA/LAMA en función pulmonar y riesgo de exacerbación vs. LABA/CIS (esta última con mayor riesgo de neumonía), 4) mayores beneficios de la terapia LAMA/LABA/CIS comparada con LABA/LAMA sobre el riesgo de exacerbaciones moderadas-severas. En relación al rol de los eosinófilos para guiar el uso de CIS: debe considerarse su retiro cuando la indicación inicial fue errada o sin respuesta, en pacientes con efectos secundarios, como neumonía y en aquellos con bajo riesgo de exacerbación con recuento de eosinófilos en sangre <300cels/μl. Incorporando estas evidencias según la gravedad de la obstrucción, síntomas y riesgo de exacerbaciones, se genera un algoritmo para el uso de medicación inhalada en la EPOC.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Montes de Oca M et al. Incorporando nuevas evidencias sobre medicamentos inhalados en la EPOC. Asociación Latinoamericana de Tórax (ALAT) 2019. Arch Bronconeumol. 2020;56:106–113.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0270" class="elsevierStylePara elsevierViewall">The following are Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0170" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1724 "Ancho" => 2559 "Tamanyo" => 276783 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0105" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Inhaled treatment depending on the severity of COPD. ALAT-2019.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0110" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroid; LABA: long-acting β2-agonists; LAMA: long-acting antimuscarinic agents; RCT: randomized controlled trials; SABA: short-acting β-agonist; SAMA: short-acting muscarinic antagonist.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical question \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PICO question \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Search strategy with MeSH terms \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Are long-acting bronchodilators (LABA or LAMA) more effective than short-acting bronchodilators (SABA or SAMA) in patients with mild COPD? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>COPD or Chronic Obstructive Pulmonary DiseaseI = LABA or LAMAC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>SABA or SAMAO = Ø \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">a) (((((``pulmonary disease, chronic obstructive”[MeSH Terms] OR copd OR chronic obstructive pulmonary disease OR coad OR chronic obstructive airway disease OR chronic obstructive lung disease OR airflow obstruction, chronic OR airflow obstructions, chronic OR chronic airflow obstructions OR chronic airflow obstruction))))) AND (``Albuterol”[MeSH] OR salbutamol OR 2-t-Butylamino-1- AND (4-hydroxy-3-hydroxy-3-hydroxymethyl) AND phenylethanol OR ventolin OR sultanov OR albuterol sulfate OR prove it)b) (((((``pulmonary disease, chronic obstructive”[MeSH Terms] OR COPD OR Chronic Obstructive Pulmonary Disease OR COAD OR Chronic Obstructive Airway Disease OR Chronic Obstructive Lung Disease OR Airflow Obstruction, Chronic OR Airflow Obstructions, Chronic OR Chronic Airflow Obstructions OR Chronic Airflow Obstruction))))) AND (``Ipratropium”[MeSH] OR atrovent OR ALovent) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Does the combination of LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICS provide greater benefits than monotherapy with LAMA or dual bronchodilator therapy with LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>COPD or Chronic Obstructive Pulmonary DiseaseI = LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICSC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>LAMA or LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LABAO = Ø \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">((((((``pulmonary disease, chronic obstructive”[MeSH Terms] OR COPD OR Chronic Obstructive Pulmonary Disease OR COAD OR Chronic Obstructive Airway Disease OR Chronic Obstructive Lung Disease OR Airflow Obstruction, Chronic OR Airflow Obstructions, Chronic OR Chronic Airflow Obstructions OR Chronic Airflow Obstruction))))) AND ``Bronchodilator Agents”[MeSH]) AND Inhale* corticosteroids* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Does the combination of LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICS (triple therapy) provide greater benefits compared with LAMA monotherapy, combination therapy (LABA/ICS) or dual bronchodilator therapy (LABA/LAMA) in patients with COPD? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>COPD or Chronic Obstructive Pulmonary DiseaseI = LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICSC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>LAMA or LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICs or LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LABAO = Ø \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(((((``pulmonary disease, chronic obstructive”[MeSH Terms] OR COPD OR Chronic Obstructive Pulmonary Disease OR COAD OR Chronic Obstructive Airway Disease OR Chronic Obstructive Lung Disease OR Airflow Obstruction, Chronic OR Airflow Obstructions, Chronic OR Chronic Airflow Obstructions OR Chronic Airflow Obstruction))))) AND Triple Therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Which COPD patients benefit from the use of ICS in the reduction of exacerbations? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>COPD or Chronic Obstructive Pulmonary DiseaseI = inhaled corticosteroidsC = ØO<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>exacerbation* OR mortality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">((((((``pulmonary disease, chronic obstructive”[MeSH Terms] OR COPD OR Chronic Obstructive Pulmonary Disease OR COAD OR Chronic Obstructive Airway Disease OR Chronic Obstructive Lung Disease OR Airflow Obstruction, Chronic OR Airflow Obstructions, Chronic OR Chronic Airflow Obstructions OR Chronic Airflow Obstruction)))) AND Inhale* corticosteroid*) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In which patients can ICS be safely withdrawn? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>COPD or Chronic Obstructive Pulmonary DiseaseI = ((withdrawal of ICS) OR (withdrawal of corticoid*))C = ØO = Ø \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">((((``pulmonary disease, chronic obstructive”[MeSH Terms] OR COPD OR Chronic Obstructive Pulmonary Disease OR COAD OR Chronic Obstructive Airway Disease OR Chronic Obstructive Lung Disease OR Airflow Obstruction, Chronic OR Airflow Obstructions, Chronic OR Chronic Airflow Obstructions OR Chronic Airflow Obstruction)))) AND Withdra* AND Inhale* AND corticosteroid* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2235529.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Search strategy (Trip Database and MeSH terms key words).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0115" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroid; LABA: long-acting β2-agonists; LAMA: long-acting antimuscarinic agents; RCT: randomized controlled trials; SABA: short-acting β-agonist; SAMA: short-acting muscarinic antagonist.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical question \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total references selected \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total references retrieved from the Trip Database \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total references retrieved from MeSH \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total references selected to answer the question \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of studies selected \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Are long-acting bronchodilators (LABA or LAMA) more effective than short-acting bronchodilators (SABA or SAMA) in patients with mild COPD? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">485 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">465 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Does the combination of LABA plus ICS provide greater benefits than monotherapy with LAMA or dual bronchodilator therapy with LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">238 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">230 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23–27</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Does the combination of LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>CIS (triple therapy) provide greater benefits compared with LAMA monotherapy, combination therapy (LABA/ICS) or dual bronchodilator therapy (LABA/LAMA) in patients with COPD? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">193 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">181 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a>5 RCTs<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4,32–34</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Which COPD patients benefit from the use of ICS in the reduction of exacerbations? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">338 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">246 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,36,37</span></a>2 RCTs<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,38</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In which patients can ICS be safely withdrawn? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">588 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">341 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">247 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 meta-analysis<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>2 RCTs<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46,47</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2235528.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Number and type of studies selected to answer clinical questions.</p>" ] ] 3 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.zip" "ficheroTamanyo" => 54919 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:58 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "[1]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.D. Pavord" 1 => "S. Lettis" 2 => "N. Locantore" 3 => "S. Pascoe" 4 => "P.W. Jones" 5 => "J.A. Wedzicha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2015-207021" "Revista" => array:7 [ "tituloSerie" => "Thorax." "fecha" => "2016" "volumen" => "71" "numero" => "2" "paginaInicial" => "118" "paginaFinal" => "125" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26585525" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "[2]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Bafadhel" 1 => "S. Peterson" 2 => "M.A. De Blas" 3 => "P.M. Calverley" 4 => "S.I. Rennard" 5 => "K. Richter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(18)30006-7" "Revista" => array:7 [ "tituloSerie" => "Lancet Respir Med." "fecha" => "2018" "volumen" => "6" "numero" => "2" "paginaInicial" => "117" "paginaFinal" => "126" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29331313" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "[3]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Lipson" 1 => "F. Barnhart" 2 => "N. Brealey" 3 => "J. Brooks" 4 => "G.J. Criner" 5 => "N.C. Day" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1602003" "Revista" => array:4 [ "tituloSerie" => "N Engl J Med." "fecha" => "2018" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27040451" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022510X16307535" "estado" => "S300" "issn" => "0022510X" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "[4]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Papi" 1 => "J. Vestbo" 2 => "L. Fabbri" 3 => "M. Corradi" 4 => "H. Prunier" 5 => "G. Cohuet" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet (London, England)." "fecha" => "2018" "volumen" => "391" "numero" => "10125" "paginaInicial" => "1076" "paginaFinal" => "1084" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "[5]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M.A. Calverley" 1 => "A.R. Anzueto" 2 => "K. Carter" 3 => "L. Grönke" 4 => "C. Hallmann" 5 => "C. Jenkins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(18)30102-4" "Revista" => array:7 [ "tituloSerie" => "Lancet Respir Med." "fecha" => "2018" "volumen" => "6" "numero" => "5" "paginaInicial" => "337" "paginaFinal" => "344" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29605624" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "[6]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía de práctica clínica de la enfermedad pulmonar obstructiva crónica (EPOC) ALAT-2014: Preguntas y respuestas" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Montes de Oca" 1 => "M.V. López Varela" 2 => "A. Acuña" 3 => "E. Schiavi" 4 => "M.A. Rey" 5 => "J. Jardim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.arbres.2014.11.017" "Revista" => array:8 [ "tituloSerie" => "Arch Bronconeumol." "fecha" => "2015" "volumen" => "51" "numero" => "8" "paginaInicial" => "403" "paginaFinal" => "416" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25596991" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0920121114002265" "estado" => "S300" "issn" => "09201211" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "[7]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of COPD in five Colombian cities situated at low, medium, and high altitude (PREPOCOL study)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Caballero" 1 => "C.A. Torres-Duque" 2 => "C. Jaramillo" 3 => "F. Bolívar" 4 => "F. Sanabria" 5 => "P. Osorio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.07-1361" "Revista" => array:7 [ "tituloSerie" => "Chest." "fecha" => "2008" "volumen" => "133" "numero" => "2" "paginaInicial" => "343" "paginaFinal" => "349" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17951621" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "[8]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of COPD in 6 Urban Clusters in Argentina: The EPOC.AR Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.L. Echazarreta" 1 => "S.J. Arias" 2 => "R. Del Olmo" 3 => "E.R. Giugno" 4 => "F.D. Colodenco" 5 => "S.C. Arce" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.arbres.2017.09.018" "Revista" => array:7 [ "tituloSerie" => "Arch Bronconeumol." "fecha" => "2018" "volumen" => "54" "numero" => "5" "paginaInicial" => "260" "paginaFinal" => "269" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29221827" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "[9]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.S. Buist" 1 => "M.A. McBurnie" 2 => "W.M. Vollmer" 3 => "S. Gillespie" 4 => "P. Burney" 5 => "D.M. Mannino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(07)61377-4" "Revista" => array:8 [ "tituloSerie" => "Lancet." "fecha" => "2007" "volumen" => "370" "numero" => "9589" "paginaInicial" => "741" "paginaFinal" => "750" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17765523" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022510X1000362X" "estado" => "S300" "issn" => "0022510X" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "[10]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of chronic obstructive pulmonary disease and variation in risk factors across four geographically diverse resource-limited settings in Peru" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Jaganath" 1 => "J.J. Miranda" 2 => "R.H. Gilman" 3 => "R.A. Wise" 4 => "G.B. Diette" 5 => "C.H. Miele" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12931-015-0198-2" "Revista" => array:6 [ "tituloSerie" => "Respir Res." "fecha" => "2015" "volumen" => "16" "numero" => "1" "paginaInicial" => "40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25889777" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "[11]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Zhou" 1 => "N. Zhong" 2 => "X. Li" 3 => "S. Chen" 4 => "J. Zheng" 5 => "D. Zhao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1700228" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med." "fecha" => "2017" "volumen" => "377" "numero" => "10" "paginaInicial" => "923" "paginaFinal" => "935" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28877027" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "[12]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluticasone Furoate, Vilanterol, and Lung Function Decline in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M.A. Calverley" 1 => "J.A. Anderson" 2 => "R.D. Brook" 3 => "C. Crim" 4 => "N. Gallot" 5 => "S. Kilbride" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201610-2086OC" "Revista" => array:7 [ "tituloSerie" => "Am J Respir Crit Care Med." "fecha" => "2018" "volumen" => "197" "numero" => "1" "paginaInicial" => "47" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28737971" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "[13]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Cheyne" 1 => "M.J. Irvin-Sellers" 2 => "J. White" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Cochrane Database Syst Rev." "fecha" => "2015" "volumen" => "2015" "numero" => "9" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "[14]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Appleton" 1 => "T. Jones" 2 => "P. Poole" 3 => "L. Pilotto" 4 => "R. Adams" 5 => "T.J. Lasserson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane database Syst Rev." "fecha" => "2006" "numero" => "3" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "[15]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A 4-year trial of tiotropium in chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.P. Tashkin" 1 => "B. Celli" 2 => "S. Senn" 3 => "D. Burkhart" 4 => "S. Kesten" 5 => "S. Menjoge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0805800" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med." "fecha" => "2008" "volumen" => "359" "numero" => "15" "paginaInicial" => "1543" "paginaFinal" => "1554" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18836213" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "[16]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.S. Ismaila" 1 => "E.L. Huisman" 2 => "Y.S. Punekar" 3 => "A. Karabis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S92412" "Revista" => array:7 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2015" "volumen" => "10" "paginaInicial" => "2495" "paginaFinal" => "2517" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26604738" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673616007376" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "[17]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled glycopyrrolate for the treatment of chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.P. Tashkin" 1 => "N.J. Gross" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S162646" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2018" "volumen" => "13" "paginaInicial" => "1873" "paginaFinal" => "1888" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29928118" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "[18]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population-based study of LAMA monotherapy effectiveness compared with LABA/LAMA as initial treatment for COPD in primary care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Barrecheguren" 1 => "M. Monteagudo" 2 => "M. Miravitlles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41533-018-0102-x" "Revista" => array:6 [ "tituloSerie" => "NPJ Prim care Respir Med." "fecha" => "2018" "volumen" => "28" "numero" => "1" "paginaInicial" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30266978" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "[19]" "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.M.A. Calverley" 1 => "J.A. Anderson" 2 => "B. Celli" 3 => "G.T. Ferguson" 4 => "C. Jenkins" 5 => "P.W. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa063070" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med." "fecha" => "2007" "volumen" => "356" "numero" => "8" "paginaInicial" => "775" "paginaFinal" => "789" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17314337" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "[20]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of dual bronchodilators in COPD: A review of the current evidence for indacaterol/glycopyrronium" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.H. Ficker" 1 => "K.F. Rabe" 2 => "T. Welte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pupt.2017.04.002" "Revista" => array:6 [ "tituloSerie" => "Pulm Pharmacol Ther." "fecha" => "2017" "volumen" => "45" "paginaInicial" => "19" "paginaFinal" => "33" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28389258" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "[21]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Role of Fixed-Dose Dual Bronchodilator Therapy in Treating COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Anzueto" 1 => "M. Miravitlles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjmed.2017.12.018" "Revista" => array:8 [ "tituloSerie" => "Am J Med." "fecha" => "2018" "volumen" => "131" "numero" => "6" "paginaInicial" => "608" "paginaFinal" => "622" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29305841" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022510X18302004" "estado" => "S300" "issn" => "0022510X" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "[22]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dual therapy strategies for COPD: the scientific rationale for LAMA + LABA" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.S. Cohen" 1 => "M.C. Miles" 2 => "J.F. Donohue" 3 => "J.A. Ohar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S54513" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2016" "volumen" => "11" "paginaInicial" => "785" "paginaFinal" => "797" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27143870" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "[23]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Miravitlles" 1 => "G. Urrutia" 2 => "A.G. Mathioudakis" 3 => "J. Ancochea" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12931-017-0683-x" "Revista" => array:6 [ "tituloSerie" => "Respir Res." "fecha" => "2017" "volumen" => "18" "numero" => "1" "paginaInicial" => "196" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29178871" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "[24]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dual bronchodilation in COPD: lung function and patient-reported outcomes – a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.B. Price" 1 => "A. Østrem" 2 => "M. Thomas" 3 => "T. Welte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S116719" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2016" "volumen" => "12" "paginaInicial" => "141" "paginaFinal" => "168" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28115839" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "[25]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Systematic Review of the Efficacy and Safety of a Fixed-Dose Combination of Umeclidinium and Vilanterol for the Treatment of COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.J. Rodrigo" 1 => "H. Neffen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.15-0084" "Revista" => array:7 [ "tituloSerie" => "Chest." "fecha" => "2015" "volumen" => "148" "numero" => "2" "paginaInicial" => "397" "paginaFinal" => "407" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25798635" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "[26]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Y. Oba" 1 => "S.T. Sarva" 2 => "S. Dias" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2014-206732" "Revista" => array:7 [ "tituloSerie" => "Thorax." "fecha" => "2016" "volumen" => "71" "numero" => "1" "paginaInicial" => "15" "paginaFinal" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26490732" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "[27]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of tiotropium–olodaterol fixed-dose combination in COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Derom" 1 => "G. Brusselle" 2 => "G. Joos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S92840" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2016" "volumen" => "11" "paginaInicial" => "3163" "paginaFinal" => "3177" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28008243" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "[28]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Double bronchodilation in chronic obstructive pulmonary disease: a crude analysis from a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. Lopez-Campos" 1 => "C. Calero-Acuña" 2 => "E. Márquez-Martín" 3 => "E. Quintana Gallego" 4 => "L. Carrasco-Hernández" 5 => "M. Abad Arranz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S132962" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2017" "volumen" => "12" "paginaInicial" => "1867" "paginaFinal" => "1876" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28694697" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "[29]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of LABA/LAMA fixed-dose combinations approved in the US for the management of COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Banerji" 1 => "D.A. Mahler" 2 => "N.A. Hanania" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/17476348.2016.1190276" "Revista" => array:7 [ "tituloSerie" => "Expert Rev Respir Med." "fecha" => "2016" "volumen" => "10" "numero" => "7" "paginaInicial" => "767" "paginaFinal" => "780" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27223863" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "[30]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination inhaled steroid and long-acting beta2-agonist versus tiotropium for chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.J. Welsh" 1 => "C.J. Cates" 2 => "P. Poole" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane database Syst Rev." "fecha" => "2013" "volumen" => "5" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "[31]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.A. Wedzicha" 1 => "P.M.A. Calverley" 2 => "T.A. Seemungal" 3 => "G. Hagan" 4 => "Z. Ansari" 5 => "R.A. Stockley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200707-973OC" "Revista" => array:7 [ "tituloSerie" => "Am J Respir Crit Care Med." "fecha" => "2008" "volumen" => "177" "numero" => "1" "paginaInicial" => "19" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17916806" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "[32]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of three combined pharmacological approaches with tiotropium monotherapy in stable moderate to severe COPD: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.J. Rodrigo" 1 => "V. Plaza" 2 => "J.A. Castro-Rodríguez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pupt.2011.10.006" "Revista" => array:7 [ "tituloSerie" => "Pulm Pharmacol Ther." "fecha" => "2012" "volumen" => "25" "numero" => "1" "paginaInicial" => "40" "paginaFinal" => "47" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22085775" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "[33]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Horita" 1 => "A. Goto" 2 => "Y. Shibata" 3 => "E. Ota" 4 => "K. Nakashima" 5 => "K. Nagai" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane Database Syst Rev." "fecha" => "2017" "numero" => "2" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "[34]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.J. Rodrigo" 1 => "D. Price" 2 => "A. Anzueto" 3 => "D. Singh" 4 => "P. Altman" 5 => "G. Bader" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S130482" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2017" "volumen" => "12" "paginaInicial" => "907" "paginaFinal" => "922" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28360514" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "[35]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single-inhaler triple therapy utilizing the once-daily combination of fluticasone furoate, umeclidinium and vilanterol in the management of COPD: the current evidence base and future prospects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Malerba" 1 => "M. Nardin" 2 => "G. Santini" 3 => "N. Mores" 4 => "A. Radaeli" 5 => "P. Montuschi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Ther Adv Respir Dis." "fecha" => "2018" "numero" => "12" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "[36]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Triple Therapy in COPD: What We Know and What We Don’t" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P.M.A. Calverley" 1 => "H. Magnussen" 2 => "M. Miravitlles" 3 => "J.A. Wedzicha" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "COPD J Chronic Obstr Pulm Dis." "fecha" => "2017" "volumen" => "14" "numero" => "6" "paginaInicial" => "648" "paginaFinal" => "662" ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "[37]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination inhaled steroid and long-acting beta₂-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Rojas-Reyes M.X. imen" 1 => "O.M. García Morales" 2 => "R.J. Dennis" 3 => "C. Karner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane database Syst Rev." "fecha" => "2016" "numero" => "6" ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "[38]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The efficacy and safety of triple inhaled treatment in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis using Bayesian methods" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.-S. Kwak" 1 => "E. Kim" 2 => "Jin Jang eun" 3 => "H. Jung Kim" 4 => "C.-H. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J COPD." "fecha" => "2015" "volumen" => "10" "paginaInicial" => "2365" "paginaFinal" => "2376" ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "[39]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Vestbo" 1 => "A. Papi" 2 => "M. Corradi" 3 => "V. Blazhko" 4 => "I. Montagna" 5 => "C. Francisco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(17)30188-5" "Revista" => array:7 [ "tituloSerie" => "Lancet." "fecha" => "2017" "volumen" => "389" "numero" => "10082" "paginaInicial" => "1919" "paginaFinal" => "1929" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28385353" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "[40]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "FULFIL Trial: Once-Daily Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Lipson" 1 => "H. Barnacle" 2 => "R. Birk" 3 => "N. Brealey" 4 => "N. Locantore" 5 => "D.A. Lomas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:4 [ "fecha" => "2017" "paginaInicial" => "03" "paginaFinal" => "449" "editorial" => "AJRCCM Artic Press" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "[41]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Singh" 1 => "A. Papi" 2 => "M. Corradi" 3 => "I. Pavlišová" 4 => "I. Montagna" 5 => "C. Francisco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(16)31354-X" "Revista" => array:7 [ "tituloSerie" => "Lancet." "fecha" => "2016" "volumen" => "388" "numero" => "10048" "paginaInicial" => "963" "paginaFinal" => "973" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27598678" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "[42]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled Corticosteroids for Chronic Obstructive Pulmonary Disease--The Shifting Treatment Paradigm" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Wilkie" 1 => "S. Finch" 2 => "S. Schembri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/15412555.2014.995288" "Revista" => array:7 [ "tituloSerie" => "COPD." "fecha" => "2015" "volumen" => "12" "numero" => "5" "paginaInicial" => "582" "paginaFinal" => "590" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25774769" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "[43]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled corticosteroids for chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Cazzola" 1 => "P. Rogliani" 2 => "L. Novelli" 3 => "M.G. Matera" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1517/14656566.2013.848856" "Revista" => array:7 [ "tituloSerie" => "Expert Opin Pharmacother." "fecha" => "2013" "volumen" => "14" "numero" => "18" "paginaInicial" => "2489" "paginaFinal" => "2499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24138334" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "[44]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled corticosteroids for stable chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "I.A. Yang" 1 => "M.S. Clarke" 2 => "E.H.A. Sim" 3 => "K.M. Fong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/14651858.CD003881.pub4" "Revista" => array:4 [ "tituloSerie" => "Cochrane database Syst Rev." "fecha" => "2012" "volumen" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28738443" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "[45]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined corticosteroid and long-acting beta2-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease (Review)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L.J. Nannini" 1 => "P. Poole" 2 => "S.J. Milan" 3 => "A. Kesterton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Cochrane Database Syst Rev." "fecha" => "2013" "numero" => "8" "itemHostRev" => array:3 [ "pii" => "S1552526018300724" "estado" => "S300" "issn" => "15525260" ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "[46]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intensified Therapy with Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Stolz" 1 => "H.H. Hirsch" 2 => "D. Schilter" 3 => "R. Louis" 4 => "J. Rakic" 5 => "L. Boeck" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201709-1807OC" "Revista" => array:7 [ "tituloSerie" => "Am J Respir Crit Care Med." "fecha" => "2018" "volumen" => "197" "numero" => "9" "paginaInicial" => "1136" "paginaFinal" => "1146" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29266965" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "[47]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory medication used in COPD patients from seven Latin American countries: the LASSYC study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Casas Herrera" 1 => "M. Montes de Oca" 2 => "A. Menezes" 3 => "F.C. Wehrmeister" 4 => "M.V. Lopez Varela" 5 => "L. Mendoza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S154097" "Revista" => array:7 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2018" "volumen" => "13" "paginaInicial" => "1545" "paginaFinal" => "1556" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29785104" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1552526016328941" "estado" => "S300" "issn" => "15525260" ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "[48]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of COPD in the UK primary-care setting: an analysis of real-life prescribing patterns" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Price" 1 => "D. West" 2 => "G. Brusselle" 3 => "K. Gruffydd-Jones" 4 => "R. Jones" 5 => "M. Miravitlles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S62750" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis." "fecha" => "2014" "volumen" => "9" "paginaInicial" => "889" "paginaFinal" => "904" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25210450" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "[49]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Overtreatment of COPD with inhaled corticosteroids--implications for safety and costs: cross-sectional observational study. de Torres JP, editor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. White" 1 => "H. Thornton" 2 => "H. Pinnock" 3 => "S. Georgopoulou" 4 => "H.P. Booth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0084567" "Revista" => array:5 [ "tituloSerie" => "PLoS One." "fecha" => "2013" "volumen" => "8" "numero" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24386394" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "[50]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.K. Han" 1 => "P.M. Quibrera" 2 => "E.E. Carretta" 3 => "R.G. Barr" 4 => "E.R. Bleecker" 5 => "R.P. Bowler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(17)30207-2" "Revista" => array:7 [ "tituloSerie" => "Lancet Respir Med." "fecha" => "2017" "volumen" => "5" "numero" => "8" "paginaInicial" => "619" "paginaFinal" => "626" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28668356" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "[51]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Susceptibility to exacerbation in chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Hurst" 1 => "J. Vestbo" 2 => "A. Anzueto" 3 => "N. Locantore" 4 => "H. Müllerova" 5 => "R. Tal-Singer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0909883" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med." "fecha" => "2010" "volumen" => "363" "numero" => "12" "paginaInicial" => "1128" "paginaFinal" => "1138" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20843247" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "[52]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled corticosteroids in COPD and the risk of serious pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Suissa" 1 => "V. Patenaude" 2 => "F. Lapi" 3 => "P. Ernst" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2012-202872" "Revista" => array:7 [ "tituloSerie" => "Thorax." "fecha" => "2013" "volumen" => "68" "numero" => "11" "paginaInicial" => "1029" "paginaFinal" => "1036" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24130228" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "[53]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Withdrawal of inhaled corticosteroids in COPD: A meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Calzetta" 1 => "M.G. Matera" 2 => "F. Braido" 3 => "M. Contoli" 4 => "A. Corsico" 5 => "F. Di Marco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pupt.2017.06.002" "Revista" => array:6 [ "tituloSerie" => "Pulm Pharmacol Ther." "fecha" => "2017" "volumen" => "45" "paginaInicial" => "148" "paginaFinal" => "158" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28606478" …1 ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "[54]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial" "autores" => array:1 [ 0 => array:2 [<