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Vinyoles, M. Camafort, M. Domenech, A. Coca, J. Sobrino" "autores" => array:6 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Vinyoles" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Camafort" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Domenech" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Coca" ] 4 => array:2 [ "nombre" => "J." 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Usefulness of the CODEX index" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "431" "paginaFinal" => "438" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Navarro, R. Costa, M. Rodriguez-Carballeira, S. Yun, A. Lapuente, A. Barrera, E. Acosta, C. Viñas, J.L. Heredia, P. Almagro" "autores" => array:10 [ 0 => array:3 [ "nombre" => "A." "apellidos" => "Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "R." "apellidos" => "Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Rodriguez-Carballeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "S." "apellidos" => "Yun" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Lapuente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "A." "apellidos" => "Barrera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 6 => array:3 [ "nombre" => "E." "apellidos" => "Acosta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "C." "apellidos" => "Viñas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "J.L." "apellidos" => "Heredia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:4 [ "nombre" => "P." "apellidos" => "Almagro" "email" => array:1 [ 0 => "19908pam@comb.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Mutua de Terrassa, Tarrasa, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario Mutua de Terrassa, Tarrasa, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Valoración pronóstica de mortalidad y hospitalizaciones en pacientes ambulatorios con EPOC avanzada. Utilidad del índice CODEX" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1371 "Ancho" => 1553 "Tamanyo" => 141882 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparison of areas under the curve for mortality between CODEX and BODEX.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases and has one of highest levels of morbidity and mortality worldwide.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">1</span></a> The assessment of its severity has classically been based on post bronchodilator FEV<span class="elsevierStyleInf">1</span>, stratified into several cutoff points modified by various scientific societies.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">2</span></a> More recently, the prognostic importance of other variables such as dyspnea and a history of exacerbations, especially severe ones, has been recognized.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3,4</span></a> The latest standard of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) therefore combines these 3 variables for classifying COPD into 4 groups of lesser to greater severity: A, B, C and D.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">5</span></a> This new GOLD classification can be considered a multicomponent scale whose validation has generated significant debate.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Other multidimensional indices developed in the last decade have shown better predictions of mortality and risk of exacerbations than FEV<span class="elsevierStyleInf">1</span> alone. The most validated of these and the one that has shown greatest precision is the BODE index, which is composed of 4 variables stratified into various cutoff points: body mass index — BMI — (B), FEV<span class="elsevierStyleInf">1</span> post broncodilation (O), dyspnea (D) and distance traveled in the 6-min walk test (E).<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">7</span></a> The index's limitations are that it requires a walking test, which makes it impractical for patients with limited mobility, and the difficulty of implementing it in primary care. The BODE was also developed using outpatients with COPD and low comorbidity. More recently, other multicomponent indices have been developed that do not require the walking test and that have demonstrated their usefulness in various populations with COPD. These indices include the BODEX (which replaces the walking test with the history of severe exacerbations in the previous year), ADO (age: A, dyspnea: D, obstruction: O) and DOSE (dyspnea: D, obstruction: O, smoking: S, exacerbations: E), although none of these analyze the presence of comorbidities, which are common and have significant prognostic connotations in COPD.<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">8–12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2014, the development and validation of the CODEX index was published.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> The CODEX uses the same cutoff points as the BODEX for pulmonary obstruction (O), dyspnea (D) and exacerbations in the previous year (EX) and replaces BMI (B) with the age-adjusted Charlson index.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a> In its initial publication, the CODEX demonstrated better prognostic capacity than the other indices in terms of mortality and hospital readmissions in patients hospitalized for COPD at 3 months and at 1 year.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> The CODEX was developed using a cohort of patients hospitalized for COPD exacerbation in 70 Spanish departments of internal medicine <span class="elsevierStyleMonospace">(</span>ESMI study, which was conducted by the COPD workgroup of SEMI).<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">15</span></a> Its validation and development was performed in 3 other cohorts.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">15–20</span></a> However, this index has not been tested in other populations, and, in the original study, the follow-up was limited to 1 year.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our objective was to assess the usefulness of the CODEX index in a population of outpatients with advanced COPD over a longer term <span class="elsevierStyleMonospace">(</span>up to 800 days<span class="elsevierStyleMonospace">)</span> and compare the index with other indices such as the BODEX and the GOLD classification.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We included all patients with COPD monitored by the Functional Unit for Chronic Pulmonary Disease Patients of University Hospital Mutua de Terrassa (Barcelona) between June 2012 and June 2014. This unit periodically evaluates patients with severe respiratory diseases and a high risk of decompensations. Data were prospectively collected from postbronchodilation spirometry, the modified Medical Research Council dyspnea scale (mMRC),<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a> the COPD assessment test (CAT) quality of life questionnaire,<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">22</span></a> the treatment prescribed for the COPD, the history of exacerbations and hospitalizations for COPD in the last year and comorbidity using the Charlson index.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a> The patients were classified following the GOLD (A–D) standard and according to the BODEX, with the established cutoff points. To calculate the CODEX index, we substituted the BMI of the BODEX by the age-adjusted Charlson index, adding a point for each decade of age past 50 years.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a> Finally, the Charlson score was stratified according to the original study (0–4 <span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0; 5–7 <span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1; ≥8 <span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2). The possible scores from the CODEX index could therefore vary between 0 and 10 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The follow-up data were obtained from the electronic medical history and through telephone calls. All patients were monitored by the same physician and the same nurse specialist according to the treatment standards of the Spanish COPD Guidelines (GesEPOC).<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">We assessed the time to death, to the first exacerbation and to the first hospitalization, as well as a combined variable defined as death or hospitalization for COPD exacerbation. We also conducted an analysis for individual events using the combined variable. The time was calculated from the first unit visit to the first event (death, readmission or both). For the analysis by events, the time was calculated from the first unit visit to each one of the events.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The quantitative variables are expressed as means and standard deviation (SD) and were analyzed using Student's <span class="elsevierStyleItalic">t</span>-test or Mann–Whitney's <span class="elsevierStyleItalic">U</span> test according to their distribution. The qualitative variables are listed as numbers and percentages and were analyzed with the chi-squared test.</p><p id="par0045" class="elsevierStylePara elsevierViewall">For the time-dependent variables, we used the Kaplan–Meier curves and the Cox proportional hazards analysis. When both indices (CODEX and BODEX) showed statistically significant association in the bivariate study, we constructed multivariate Cox proportional hazard models, inserting both indices along with their interaction. We calculated the receiver operating characteristic (ROC) curves, comparing the area under the curve (AUC) of the C statistic for the various indices and analyzed its significance with the DeLong method.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">24</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The study was performed within standard clinical practice and was approved by the Clinical Trials Committee of Hospital Mutua de Terrassa.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study included 80 patients (90% men), with a mean age of 73.4 (SD, 8.9) years and an FEV<span class="elsevierStyleInf">1</span> after the bronchodilator test of 39% (SD, 16%). The mean Charlson index was 2.96 (SD, 1.5) without adjusting for age and 4.92 (SD, 1.9) after adjusting for this parameter. The median follow-up was 650 days, with an interquartile range (25–75%) of 384–752 days. During this time, 17 deaths (21%) occurred. The population characteristics according to mortality are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The CODEX index was significantly associated with mortality (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.008; HR, 1.56; 95% CI: 1.12–2.15); however, the GOLD classification and the BODEX index were not significantly associated with mortality (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.07). The AUC was 0.77 (95% CI: 0.6–0.83) for the CODEX and 0.63 (95% CI: 0.52–0.74) for the BODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.0001) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Seventy-one percent of the patients presented at least 1 outpatient exacerbation, with a mean of 1.9 (SD, 1.2) episodes. None of the indices were significantly associated with the presence of outpatient exacerbations during the follow-up. A total of 58 patients (72.5%) required at least 1 hospitalization for COPD exacerbation during the follow-up, with a mean number of hospitalizations of 2 (SD, 2.21). In the bivariate study, the CODEX index was significantly associated with the risk of hospitalization (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001; HR: 1.41; 95% CI: 1.16–1.72), as was the BODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.03; HR: 1.19; 95% CI: 1.02–1.34), while the GOLD classification showed no statistical significance. The AUC was similar for the CODEX (0.70) and the BODEX (0.69).</p><p id="par0065" class="elsevierStylePara elsevierViewall">When the relationship with the combined variable was analyzed, the CODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.003; HR: 1.27; 95% CI: 1.1–1.5) and BODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03; HR: 1.19; 95% CI: 1.02–1.34) indices once again showed a statistically significant relationship, with no differences in the AUC (0.65 and 0.62, respectively), while the GOLD classification had a <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.049. After adjusting both indices and their interaction in a multivariate Cox proportional hazards model, only the CODEX maintained an independent relationship with the combined variable (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.03) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The relationship between the combined variable and the CODEX stratified in terciles is represented graphically in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">There were 187 events during the follow-up. Both the CODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001; HR: 1.17; 95% CI: 1.1–1.27) and BODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.02; HR: 1.12; 95% CI: 1.02–1.23) indices were associated with the total number of events, while the new GOLD classification showed no significance. The CODEX curves for events grouped by terciles are shown in the <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>. The relationship between the various components of the CODEX and BODEX indices, in terms of mortality, the combined variable and the analysis by events, is shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. The comparison between the number of events and the stratified CODEX is shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>. After adjusting the number of events in the Cox regression for the CODEX and BODEX indices, adding the interaction between them, only the CODEX maintained its statistical significance (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The CAT scale of health-related quality of life showed no relationship with mortality, the number of hospitalizations or the combined variable. The walking test was not performed on 50 patients (62%). The relationship between the BODE and mortality, readmissions and the combined variable was therefore not studied.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Our study confirmed the validity of the CODEX index for the prognostic assessment of patients with COPD, using a population different from that included in the original study conducted with patients hospitalized for exacerbations. Our study also had a longer follow-up period. As far as we know, this is the first study to confirm the validity of this index after its publication.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">13,25</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The prognostic assessment of COPD has been the subject of study in various publications.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">26</span></a> The BODE was the first clinically useful index for assessing these patients’ prognosis, using 4 stratified variables: BMI (B), FEV<span class="elsevierStyleInf">1</span> postbronchodilation (O), dyspnea (D) and distance traveled in the 6-min walk test (E). The BODE has been validated in numerous subsequent studies, including hospitalized populations.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">7,20</span></a> More recently, other multicomponent indices have been developed using various populations. The first of these was the so-called BODEX index, which substituted the walking test with the history of severe exacerbations in the previous year.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">8</span></a> The DOSE (dyspnea, obstruction, smoking and exacerbations) index was designed to predict exacerbations, although it has also been related to mortality and has been implemented mostly in primary care.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">10,27</span></a> The ADO (age, dyspnea and FEV<span class="elsevierStyleInf">1</span>) index has also shown good prognostic reliability, although a number of authors have questioned the weight of age in this index, given that, despite being an excellent predictor of mortality, age is not modifiable.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">9,11,28,29</span></a> All of these indices have been developed in populations with outpatient COPD, except for a new scale called DECAF (dyspnea, eosinopenia, condensation, acidemia and atrial fibrillation) designed to assess hospital mortality in patients with COPD. However, this scale excluded patients with severe comorbidity.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">30</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Despite the recognized impact of comorbidity in COPD, none of these prognostic scales incorporates its assessment. Instead, they exclude patients with severe associated diseases. These scales might therefore not represent the population commonly hospitalized for COPD exacerbation, in which multiple diseases is the rule, a condition that is closely related to the prognosis.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">15</span></a> With this objective, the CODEX index was designed and validated for patients hospitalized for COPD and incorporated comorbidity. In its first publication, this index showed better calibration for predicting readmissions and mortality at 1 year in this population.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> The present study confirms these findings in a different population and with a longer follow-up.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In the cohort analyzed in our study, the CODEX index was superior to the BODEX index in assessing the risk of mortality, in the combined variable (after adjusting for confounding variables) and in the analysis by events. Nevertheless, the BODEX index also showed a statistically significant relationship with the combined variable and the analysis by events. Therefore, its usefulness is inarguable, and it remains an alternative to BODE for cases in which the walking test is unavailable.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a> The only difference between CODEX and BODEX is the substitution of BMI by the age-adjusted Charlson index. Although both low weight and comorbidity are associated with a poorer prognosis in COPD, comorbidity appears to be more important in the risk of mortality and hospitalization.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">15,31</span></a> In fact, as shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, the stratified BMI for the BODEX did not achieve statistical significance in any of the analyses performed, in contrast to that observed with the Charlson index.</p><p id="par0100" class="elsevierStylePara elsevierViewall">We believe that the usefulness of the various indices depends largely on the study population and the study objectives. For example, the BODE is more sensitive to changes following an exacerbation or with respiratory rehabilitation and is the index of choice for assessing the results of a pulmonary rehabilitation program.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a> For outpatient populations with less comorbidity, the BODEX is simpler to calculate than the BODE. In contrast, for hospitalized populations with added comorbidity, the CODEX is probably a better prognostic scale. Recently, a consensus document between the European and American respiratory societies identified the implementation of comparative studies between the various COPD prognostic indices as a priority research objective.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">33</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Finally, we should note that for our population neither the GOLD scale nor the CAT index proved to be useful in assessing the risk of mortality or hospitalizations. Various studies have reported the limitations of the GOLD scale as a predictor of mortality.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">6</span></a> In fact, survival is lower for patients in group B (less severe) than for those in group C (more severe), which indicates that group B includes patients with less spirometric involvement but with more comorbidities and therefore poorer prognosis. The GOLD standard, meanwhile, considers that the assessment of symptoms can be performed interchangeably with the mMRC dyspnea scale or with CAT. However, the use of one or the other scale changes the severity category in which the patients are classified, and, in contrast to the mMRC dyspnea scale, the CAT has shown no relationship with mortality.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3,34,35</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Our study has a number of limitations, the first of which is the sample size. The number of included patients and the follow-up were sufficient to demonstrate the validity of the CODEX; however, given the high number of deaths and hospitalizations, some variables might have achieved statistical significance with a larger sample size. The low number of women included is common to most studies performed in Spain and limits the extrapolation of results to other populations.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In conclusion, our study reinforces the usefulness of the CODEX index in the prognostic assessment of patients with advanced COPD, although new validations from other studies are needed.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres797708" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec795732" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres797707" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec795731" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-04-22" "fechaAceptado" => "2015-06-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec795732" "palabras" => array:6 [ 0 => "Chronic obstructive pulmonary disease" 1 => "Prognosis" 2 => "Mortality" 3 => "Hospitalization" 4 => "Comorbidity" 5 => "Multimorbidity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec795731" "palabras" => array:6 [ 0 => "Enfermedad pulmonar obstructiva crónica" 1 => "Pronóstico" 2 => "Mortalidad" 3 => "Hospitalización" 4 => "Comorbilidad" 5 => "Multimorbilidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To validate the CODEX index in outpatients with advanced chronic obstructive pulmonary disease (COPD).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We studied all patients with COPD treated in a chronic respiratory disease unit. We calculated the BODEX and CODEX indices and their relationship with mortality, hospitalisations or both and performed an analysis by number of events (mortality and/or readmissions), using the Cox proportional hazards analysis.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 80 patients (90% men) with a mean age of 73.4 years. The mean follow-up was 656 days, with an interquartile range (25–75%) of 417–642 days. Seventeen patients died (21%) and 57 (71.3%) required hospitalization for COPD. The CODEX index was significantly related to mortality (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.008; HR: 1.56; 95% CI: 1.1–2.15), hospitalisations (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.01; HR: 1.35; 95% CI: 1.13–1.62) and the combined variable (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.03; HR: 1.27; 95% CI: 1.1–1.5). The BODEX index was not associated with mortality (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.17) but was associated with hospitalization (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001; HR: 1.4; 95% CI: 1.15–1.73) and the combined variable (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.03; HR: 1.2; 95% CI: 1.02–1.34). There were 187 events during follow-up. Both the CODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001; HR: 1.17; 95% CI: 1.1–1.27) and BODEX (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.02; HR: 1.12; 95% CI: 1.02–1.23) indices were related to the number of events. However, after adjusting for the interaction between the 2 indices, only the CODEX index maintained statistical significance for the combined variable for patients (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.03) and in the analysis by number of events (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Both the CODEX and BODEX indices are useful for predicting hospitalisations, although the prognostic ability of the CODEX index is greater than that of the BODEX index, both for mortality and hospitalisations.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Validar el índice CODEX en pacientes ambulatorios con EPOC avanzada.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se estudió a todos los pacientes con EPOC controlados en una unidad de pacientes crónicos respiratorios. Se calcularon los índices BODEX y CODEX y su relación con mortalidad, hospitalizaciones o ambas, y se realizó un análisis por número de eventos (mortalidad o reingresos), mediante el análisis de riesgos proporcionales de Cox.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyó a 80 pacientes (90% varones) con una edad media de 73,4 años. El seguimiento medio fue de 656 días con un rango intercuartílico (25-75%) de 417-642 días. Un total de 17 pacientes fallecieron (21%) y 57 (71,3%) requirieron hospitalización por EPOC. El índice CODEX se relacionó significativamente con la mortalidad (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,008; HR: 1,56; IC 95%: 1,1-2,15), el ingreso hospitalario (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,01; HR: 1,35; IC 95%: 1,13-1,62) y la variable combinada (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,03; HR: 1,27; IC 95%: 1,1-1,5). El BODEX no se asoció con la mortalidad (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,17), pero sí con los ingresos (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001; HR: 1,4; IC 95%: 1,15-1,73) y la variable combinada (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,03; HR: 1,2; IC 95%: 1,02-1,34). Durante el seguimiento se produjeron 187 eventos. Tanto el índice CODEX (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001; HR:1,17; IC 95%:1,1-1,27) como el BODEX (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,02; HR: 1,12; IC 95%: 1,02-1,23) se relacionaron con el número de eventos, aunque tras ajustar por la interacción entre ambos índices solo el CODEX conservó la significación estadística para la variable combinada por pacientes (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,03) y en el análisis por número de eventos (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Tanto el CODEX como el BODEX son útiles en la predicción de ingresos hospitalarios, aunque la capacidad pronóstica del CODEX es superior al BODEX tanto en mortalidad como en ingresos hospitalarios.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as: Navarro A, Costa R, Rodriguez-Carballeira M, Yun S, Lapuente A, Barrera A, et al. Valoración pronóstica de mortalidad y hospitalizaciones en pacientes ambulatorios con EPOC avanzada. Utilidad del índice CODEX. Rev Clin Esp. 2015;215:431–438.</p>" ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1371 "Ancho" => 1553 "Tamanyo" => 141882 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparison of areas under the curve for mortality between CODEX and BODEX.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1047 "Ancho" => 1560 "Tamanyo" => 96757 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Kaplan–Meier curves between the combined variable and the CODEX stratified in terciles.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1178 "Ancho" => 1576 "Tamanyo" => 100360 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Kaplan–Meier curves between the number of events and the CODEX stratified in terciles.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1522 "Ancho" => 2168 "Tamanyo" => 115309 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Relationship between the number of events and the stratified CODEX.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CODEX, comorbidity, obstruction, dyspnea, exacerbations; mMRC, modified dyspnea scale of the Medical Research Council; PBD, postbronchodilation.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CODEX \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Domain \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Comorbidity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Charlson<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5–7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">O \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Obstruction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span>% PBD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50–64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36–49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≤35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dyspnea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">mMRC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">EX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exacerbations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exacerbations<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337978.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Charlson Index adding a point for each decade starting at 50 years of age.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Severe exacerbations in the last year (hospitalization or emergency department visit for COPD exacerbation).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Variables, scores and cutoff points of the CODEX index.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">The analysis was performed using the comparison of means or the chi-squared test.</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">LABA, long-acting betamimetics; LAMA, long-acting anticholinergics.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Died (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Living (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>63) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>80) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Sex, males (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 (70%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 (90%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Age, y (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.1 (7.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.1 (8.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73.4 (8.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">% (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.6 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.6 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.51 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">FVC % (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.36 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">/FVC (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.2 (11.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.6 (12.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Dyspnea (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.9 (0.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.6 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.7 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Smoking</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Current \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exsmoker \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 (71%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 (91%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Packs/year<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57.8 (44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.7 (33.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56.2 (35.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.64 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">CAT (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19.2 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.1 (5.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">BMI (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.8 (4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.7 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.1 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.026 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Hospitalizations (SD)</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 (2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.7 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Charlson score without age (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.7 (1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Charlson score with age (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.3 (2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.6 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.9 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">BODEX (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.6 (1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.9 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.1 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">CODEX (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.7 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.8 (1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">GOLD</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (18%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (22.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (21.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (82%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 (71%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 (73.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Drugs</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Inhaled corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 (98.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79 (98%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LABA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 (98%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79 (98%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LAMA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (94%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 (98%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79 (98%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Roflumilast \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (12.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (16%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (15.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Theophylline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (12%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (9.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Azithromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (31.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (31.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (31.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.3 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.2 (3.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.4 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.58 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337980.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Smokers and exsmokers.</p>" ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Hospitalizations or emergency department visits for COPD exacerbation.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Population characteristics according to the survival.</p>" ] ] 6 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Combined variable</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1–4.52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.47–1.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX*BODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.85–1.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Analysis by events</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.29–2.75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.68–1.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX*BODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9–1.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337979.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Interaction analysis. Analysis model of Cox proportional hazards.</p>" ] ] 7 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Analysis performed with the Cox proportional hazards model.</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">B, body mass index; D, dyspnea measured with the stratified mMRC scale; EX, stratified severe exacerbations in the previous year; O, stratified FEV1 postbronchodilator.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mortality</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AUC \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">B</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4–7.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">C</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.49–7.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">O</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78–2.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">D</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69–3.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">EX</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78–3.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">BODEX</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.97–1.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">CODEX</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.12–2.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Combined</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17–1.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.94–2.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>O \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.89–1.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86–2.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>EX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1–2.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.02–1.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.08–1.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Events</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5–1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.13–1.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>O \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.93–1.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.96–1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>EX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.16–1.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.018 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.02–1.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CODEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.07–1.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337977.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Comparison of the various components of BODEX and CODEX.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0185" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. 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