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Murphy, Nicholas Hart" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Patrick B." "apellidos" => "Murphy" ] 1 => array:2 [ "nombre" => "Nicholas" "apellidos" => "Hart" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S030028961730443X" "doi" => "10.1016/j.arbres.2017.12.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030028961730443X?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212918300260?idApp=UINPBA00003Z" "url" => "/15792129/0000005400000003/v3_201803080856/S1579212918300260/v3_201803080856/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1579212918300144" "issn" => "15792129" "doi" => "10.1016/j.arbr.2018.01.014" "estado" => "S300" "fechaPublicacion" => "2018-03-01" "aid" => "1742" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2018;54:134-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1736 "formatos" => array:3 [ "EPUB" => 135 "HTML" => 1113 "PDF" => 488 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Prevalence and Features of Asthma in Young Adults in Urban Areas of Argentina" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "134" "paginaFinal" => "139" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prevalencia y características clínicas del asma en adultos jóvenes en zonas urbanas de Argentina" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "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" => 885 "Ancho" => 1667 "Tamanyo" => 81150 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study flow chart. National survey of the prevalence of asthma in adults. Argentina, 2015.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sergio J. Arias, Hugo Neffen, Juan Carlos Bossio, Carina A. Calabrese, Alejandro J. Videla, Gustavo A. Armando, Joseph M. Antó" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Sergio J." "apellidos" => "Arias" ] 1 => array:2 [ "nombre" => "Hugo" "apellidos" => "Neffen" ] 2 => array:2 [ "nombre" => "Juan Carlos" "apellidos" => "Bossio" ] 3 => array:2 [ "nombre" => "Carina A." "apellidos" => "Calabrese" ] 4 => array:2 [ "nombre" => "Alejandro J." "apellidos" => "Videla" ] 5 => array:2 [ "nombre" => "Gustavo A." "apellidos" => "Armando" ] 6 => array:2 [ "nombre" => "Joseph M." "apellidos" => "Antó" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289617303538" "doi" => "10.1016/j.arbres.2017.08.021" "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/S0300289617303538?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212918300144?idApp=UINPBA00003Z" "url" => "/15792129/0000005400000003/v3_201803080856/S1579212918300144/v3_201803080856/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Demographic Characteristics and Clinical Outcomes in Patients from Latin America Versus the Rest of the World: A TIOSPIR<span class="elsevierStyleSup">®</span> Post-Hoc Analysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "140" "paginaFinal" => "148" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Antonio Anzueto, Peter M.A. Calverley, Achim Mueller, Norbert Metzdorf, Michaela Haensel, José R. Jardim, Emilio Pizzichini, Horacio Giraldo, Alejandra Ramirez-Venegas, Eduardo R. Giugno" "autores" => array:10 [ 0 => array:4 [ "nombre" => "Antonio" "apellidos" => "Anzueto" "email" => array:1 [ 0 => "anzueto@uthscsa.edu" ] "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" => "Peter M.A." "apellidos" => "Calverley" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Achim" "apellidos" => "Mueller" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Norbert" "apellidos" => "Metzdorf" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Michaela" "apellidos" => "Haensel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "José R." "apellidos" => "Jardim" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 6 => array:3 [ "nombre" => "Emilio" "apellidos" => "Pizzichini" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 7 => array:3 [ "nombre" => "Horacio" "apellidos" => "Giraldo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 8 => array:3 [ "nombre" => "Alejandra" "apellidos" => "Ramirez-Venegas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 9 => array:3 [ "nombre" => "Eduardo R." "apellidos" => "Giugno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Pulmonary/Critical Care, University of Texas and South Texas Veterans Health Care System, San Antonio, TX, USA" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Biostatistics and Data Sciences Europe, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Respiratory Medicine, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Respiratory Division, Federal University of São Paulo, São Paulo, Brazil" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "The Federal University of Santa Catarina, Florianópolis, Brazil" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Almirante Colón Medical Center, Clínica del Country, Bogotá, Colombia" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Tobacco Smoking and COPD Research Department, National Institute of Respiratory Diseases, Mexico City, Mexico" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Hospital Zonal Especializado de Agudos y Crónicos “Dr. Antonio Cetrángolo”, Buenos Aires, Argentina" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Características demográficas y resultados clínicos en pacientes de Latinoamérica respecto al resto del mundo: un análisis <span class="elsevierStyleItalic">post-hoc</span> de TIOSPIR<span class="elsevierStyleSup">®</span>" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2369 "Ancho" => 2893 "Tamanyo" => 564120 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Time to first moderate-to-severe COPD exacerbation by region and according to baseline characteristics (on-treatment analysis).</p> <p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Events were counted from randomization to drug stop date<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1 day.</p> <p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">BL, baseline; BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HR, hazard ratio; ICS, inhaled corticosteroid; LABA, long-acting β<span class="elsevierStyleInf">2</span>-agonist; RoW, rest of the world.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic obstructive pulmonary disease (COPD) represents an enormous health burden worldwide. Its prevalence is relatively high in Latin America, affecting an estimated 14.3%<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> of the population versus 9.2%<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a> in the rest of the world (RoW). A substantial proportion of Latin American patients had experienced an exacerbation (18.2%),<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a> and respiratory causes, including COPD, are amongst the leading cause of mortality in this region.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> Smoking is a behaviour that is seemingly ingrained in Latin American culture,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">5</span></a> with smokers from Latin America constituting 8%–10% of tobacco smokers globally.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> Solid fuels are used by 30%–75% of households<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">7</span></a> (traditionally in rural areas<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a>) and contribute to mortality rates similar to those observed in tobacco smokers.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">9</span></a> Management guidelines for COPD recognize that curbing the smoking epidemic<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">10,11</span></a> and reducing exposure to pollutants<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> are necessary to lower COPD risk in developing countries, but do not detail regional differences in risk, outcomes, or treatment options.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The TIOtropium Safety and Performance In Respimat<span class="elsevierStyleSup">®</span> (TIOSPIR<span class="elsevierStyleSup">®</span>) study demonstrated similar efficacy and safety profiles between tiotropium Respimat<span class="elsevierStyleSup">®</span> (2.5 or 5<span class="elsevierStyleHsp" style=""></span>μg) and tiotropium HandiHaler<span class="elsevierStyleSup">®</span> 18<span class="elsevierStyleHsp" style=""></span>μg, with respect to risk of mortality and risk of exacerbation.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a> A recent TIOSPIR<span class="elsevierStyleSup">®</span> subanalysis demonstrated similar mortality rates in Asian patients versus RoW. Although exacerbation rates were lower in Asia, a higher proportion of patients had severe exacerbations than in RoW.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The purpose of this post-hoc analysis was to determine whether there are differences in the baseline characteristics, mortality, exacerbations, cardiac adverse event, and serious adverse event (SAE) outcomes of patients from Latin American geographical region versus RoW in the TIOSPIR<span class="elsevierStyleSup">®</span> trial.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">TIOSPIR<span class="elsevierStyleSup">®</span> (<a id="intr0005" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT01126437">NCT01126437</a>) was a large (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17<span class="elsevierStyleHsp" style=""></span>135), long-term (2–3-year), randomized, double-blind, parallel-group, double-dummy, event-driven trial in patients with COPD comparing the safety and efficacy of once-daily tiotropium (SPIRIVA<span class="elsevierStyleSup">®</span> [Boehringer Ingelheim, Ingelheim am Rhein, Germany]) via Respimat<span class="elsevierStyleSup">®</span> 5<span class="elsevierStyleHsp" style=""></span>μg (2 inhalations of 2.5<span class="elsevierStyleHsp" style=""></span>μg), and 2.5<span class="elsevierStyleHsp" style=""></span>μg (2 inhalations of 1.25<span class="elsevierStyleHsp" style=""></span>μg), or via HandiHaler<span class="elsevierStyleSup">®</span> 18<span class="elsevierStyleHsp" style=""></span>μg; 17<span class="elsevierStyleHsp" style=""></span>116 patients constituted the as-treated population and were included in this analysis. The study design, detailed methods, and primary results were published previously.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12,14</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">All participants had a confirmed diagnosis of COPD (forced expiratory volume in 1 second [FEV<span class="elsevierStyleInf">1</span>] ≤70% predicted and FEV<span class="elsevierStyleInf">1</span>/forced vital capacity ≤0.70), were aged ≥40 years, and had ≥10 pack-years of smoking history.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> Patients with concomitant cardiac diseases were included in the study, except those with recent (≤6 months) myocardial infarction (MI), severe arrhythmia, or a change in drug therapy within the previous year; or hospitalization for cardiac failure within the previous year.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> All usual background treatments for COPD, except other inhaled anticholinergics, were allowed.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The geographical region of Latin America enrolled patients in Argentina, Brazil, Colombia, Guatemala, Mexico, Panama, and Peru.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Outcome measures</span><p id="par0035" class="elsevierStylePara elsevierViewall">Outcomes of interest in this analysis were time to all-cause death, time to first moderate-to-severe or severe exacerbation, time to major adverse cardiovascular events (MACE) and fatal MACE, and SAEs for patients in Latin America versus RoW.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Assessments</span><p id="par0040" class="elsevierStylePara elsevierViewall">An independent mortality adjudication committee, blinded to treatment assignments attributed the cause of each death.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> Non-fatal stroke and MI (included in MACE) were reported by study investigators and verified for classification accuracy by central reviewers who were blinded to treatment assignment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Exacerbations were defined as the worsening of ≥2 major respiratory symptoms (dyspnoea, cough, sputum, chest tightness, or wheezing) for ≥3 days and requiring specified treatment changes. Moderate-to-severe exacerbations required a prescription for antibiotics, systemic corticosteroids, or both (with no hospitalization); severe exacerbations required hospitalization. The onset of exacerbation was defined as the onset of the first recorded symptom; the end of exacerbation was decided by the investigator, based on clinical judgment.</p><p id="par0050" class="elsevierStylePara elsevierViewall">A composite endpoint of MACE was included in the analyses, comprising stroke, transient ischaemic attack (TIA), MI, sudden death, cardiac death, sudden cardiac death, or fatal event in the system organ classes (SOCs) for cardiac and vascular disorders. SOCs were defined according to the Medical Dictionary for Regulatory Activities standardizing attributions of AEs globally.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Based on similar efficacy and safety results among the tiotropium treatment arms in the primary analysis,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a> data were pooled for this post-hoc exploratory analysis.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Baseline characteristics discriminating between patients in Latin America and RoW were identified and compared descriptively.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to events by region were calculated using a Cox proportional hazards regression model without covariate adjustment, and displayed via Kaplan–Meier plots. A negative binomial regression model was used to estimate the number of exacerbations. HRs for time to death and time to moderate-to-severe exacerbation analyses, by region and baseline characteristics, are shown as forest plots. Additional analyses of time to death and moderate-to-severe exacerbation, severe exacerbations, and MACE were adjusted for covariates including age, post-bronchodilator FEV<span class="elsevierStyleInf">1</span>% predicted, gender, exacerbation history, smoking history (pack-years), body mass index (BMI), and history of cardiac disorders, MI, coronary artery disease/ischaemic heart disease (CAD/IHD), cardiac arrhythmia, heart failure (class I–IV), and stroke/TIA.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Incidence rates, incidence rate ratios (IRRs), and 95% CIs for causes of death were calculated. SAEs are provided in the Supplementary Material.</p><p id="par0075" class="elsevierStylePara elsevierViewall">For the mortality analysis (vital status), data were included if death occurred up until the study end date, irrespective of treatment discontinuation. For the exacerbation analysis (on-treatment), events were counted from randomization to drug stop date<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1 day, and for MACE to drug stop date<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>30 days.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Study population</span><p id="par0080" class="elsevierStylePara elsevierViewall">Of the TIOSPIR<span class="elsevierStyleSup">®</span> population, 1000 patients from Latin America and 16<span class="elsevierStyleHsp" style=""></span>116 patients from RoW were included (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Total exposure to tiotropium was 1855 and 32<span class="elsevierStyleHsp" style=""></span>229 patient-years for Latin America and RoW, respectively. A total of 228 (22.8%) patients from Latin America and 3689 (22.9%) patients from RoW discontinued prematurely from trial medication. Reasons for premature discontinuation were similar, and mainly due to AEs, with respiratory disorders (including COPD) being the most common AEs, followed by neoplasms, and infections and infestations.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a> Vital status follow-up was complete for 99.1% and 99.8% of patients from Latin America and RoW, respectively.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Baseline characteristics</span><p id="par0085" class="elsevierStylePara elsevierViewall">At baseline, patients enrolled in Latin America were comparatively older (higher proportion of patients aged ≥70 years), and had higher mean pack-years of smoking history than those in RoW, although a lower percentage were current smokers (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). A higher proportion of patients in Latin America had COPD exacerbation in the year prior to the trial than those in RoW. Latin American patients were more likely to have very severe COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stage IV) versus RoW (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Fewer Latin American patients had a history of cardiac disorders, or were receiving cardiovascular medication at baseline versus RoW (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The proportions of patients receiving long-acting muscarinic antagonist (LAMA) or long-acting β<span class="elsevierStyleInf">2</span>-agonist (LABA) at baseline were lower in Latin America than in RoW; however, they were more likely to receive inhaled corticosteroids (ICS) (with or without LABA) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Mortality</span><p id="par0090" class="elsevierStylePara elsevierViewall">During the study, a greater proportion of patients died in the Latin American population (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>100 [10.0%]) versus RoW (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1200 [7.4%]) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A). Analysis of time to death confirmed that patients in Latin America had a higher risk of death than those in RoW (HR [95% CI]: 1.52 [1.24–1.86]) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This was also true when the analysis of time to death was adjusted for age, gender, FEV<span class="elsevierStyleInf">1</span>% predicted, exacerbation history, smoking history (pack-years), BMI, history of cardiac disorders, MI, CAD/IHD, cardiac arrhythmia, heart failure (class I–IV), and stroke/TIA (HR [95% CI]: 1.37 [1.11–1.69]) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">While the overall risk of death was increased in patients from Latin America versus RoW, regression analysis according to baseline characteristics showed that the risk of death was similar for Latin America and RoW in patients with BMI ≥30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (HR [95% CI]: 1.07 [0.58–1.96]), and patients with cardiac arrhythmia (HR [95% CI]: 1.06 [0.62–1.82]) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The largest HRs were observed in patients with GOLD Stage IV (HR [95% CI]: 1.87 [1.26–2.77]) and in those who received LABA (but no ICS) (HR [95% CI]: 1.94 [1.05–3.60]) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), however the LABA (no ICS) result is based on small patient number. Causes of death were mainly similar between the regions, except for respiratory, thoracic, and mediastinal disorders, including COPD, gastrointestinal disorders, general disorders including death due to unknown reason (sudden cardiac death and death), and infections and infestations, where the incidence rate was higher in the Latin American region versus RoW. General disorders, neoplasms, and respiratory disorders, including COPD, contributed the majority of deaths (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">COPD exacerbations</span><p id="par0100" class="elsevierStylePara elsevierVi