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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cumulative probability of being cancer free for patients with chronic obstructive pulmonary disease&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#42;Age of the patient with chronic obstructive pulmonary disease at the time of cancer diagnosis&#46; Dashed line&#58; GOLD III&#8211;IV&#46; Continuous line&#58; GOLD I&#8211;II<span class="elsevierStyleSmallCaps">&#46;</span> Log rank test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;072&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; COPD&#44; chronic obstructive pulmonary disease&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Tobacco use has been defined as the main preventable cause of premature mortality and constitutes one of the main health problems in developed countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">1&#8211;4</span></a> The ingredients of tobacco include ammonia&#44; pyridine&#44; tar&#44; polycyclic aromatic hydrocarbons and nitrosamines&#44; whose combustion releases more than 4000 hazardous substances&#44; at least 60 out of which have been demonstrated to be carcinogenic&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In addition to being responsible for 90&#37; of lung cancers&#44; tobacco smoke has been shown to have a solid relationship with the development of cancer at other sites&#44; including the oral cavity&#44; larynx&#44; esophagus&#44; bladder&#44; kidneys&#44; pancreas&#44; stomach&#44; colon&#44; rectum and cervix&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">6&#8211;11</span></a> Apart from its carcinogenic effects&#44; tobacco smoke has a role as a risk factor for the development of the main chronic cardiovascular and respiratory diseases&#44; the latter of which include disorders such as bronchial asthma&#44; respiratory infections and chronic obstructive pulmonary disease &#40;COPD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Lung cancer and COPD seem to share common environmental exposure factors beyond smoking&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">14&#8211;17</span></a> COPD is known to increase three to fivefold fold the risk of developing lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">15&#44;18&#8211;22</span></a> Chronic bronchitis&#44; emphysema and the degree of bronchial obstruction are independent risk factors for the onset of lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">18&#8211;29</span></a> Moreover&#44; various studies have demonstrated an increase in the development of extrapulmonary tumors in patients with COPD compared with smokers without obstruction&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">30&#8211;35</span></a> Although direct toxicity of tobacco-derived metabolic products may be responsible for this increase&#44; the underlying inflammatory process in a chronic disease such as COPD could play a crucial role in the carcinogenic response of various organs&#44; amplifying mutagenesis and facilitating tumor growth and subsequent metastatic spread&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">7&#44;36&#8211;39</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The incidence rate of lung cancer in patients with COPD ranges from 1&#46;4 to 16&#46;7 per 1000 person-years&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">19&#44;22&#44;40</span></a> However&#44; the exact overall incidence rate for cancer&#44; especially extrapulmonary cancer&#44; is not known&#46; The aim of this study was to determine incidence rate of both pulmonary and extrapulmonary cancer in a followed-up&#44; pulmonology outpatient population with COPD and to assess its relationship to the degree of airflow obstruction&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">An observational&#44; prospective study was conducted with a cohort of patients with COPD followed up at outpatient pulmonology clinics of the University Hospital Nuestra Se&#241;ora de Candelaria &#40;HUNSC&#41; between January 1&#44; 2012 and December 31&#44; 2015&#46; The included population represented the southern and capital area of the island of Tenerife&#44; which has a reference population of 452&#44;000 inhabitants and 22 health areas&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Inclusion criteria comprised an age over 40 years&#44; active smokers or ex-smokers with a pack-year index &#40;PYI&#41; &#8805;10 and a post-bronchodilator forced expiratory volume in 1 second &#40;FEV1&#41;&#47;forced vital capacity &#40;FVC&#41; &#60; 70&#37;&#46; Exclusion criteria were the presence of chronic respiratory disease other than COPD&#44; a previous cancer diagnosis and the presence of chronic airflow obstruction without exposure to tobacco smoke or a PYI &#60;10&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Through the computerized medical history&#44; we collected the following parameters from each patient&#58; age&#44; sex&#44; body mass index &#40;BMI&#44; i&#46;e&#46; weight in kg&#47;height in m<span class="elsevierStyleSup">2</span>&#41;&#44; smoking &#40;active smoker if the patient has smoked at least 1 cigarette in the past 6 months&#59; ex-smoker if the patient had been a smoker but had ceased for at least a continuous 6-month period&#59; non-smoker if the patient had never smoked&#41; and the intensity of the smoking by means of the PYI calculation &#40;&#91;number of daily cigarettes<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>years of smoking&#93;&#47;20&#41;&#46; Likewise&#44; the forced spirometry results FEV<span class="elsevierStyleInf">1</span>&#44; FVC and FEV<span class="elsevierStyleInf">1</span>&#47;FVC were recorded and patients stratified according to the degree of severity recorded in the 2009 GOLD guidelines<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">41</span></a> and the 2017 GOLD categories&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">42</span></a> According to the 2009 GOLD guidelines&#44; COPD severity is classified into the following stages&#58; mild &#40;stage <span class="elsevierStyleSmallCaps">I</span>&#41; FEV<span class="elsevierStyleInf">1</span> &#8805;80&#37;&#59; moderate &#40;stage <span class="elsevierStyleSmallCaps">II</span>&#41; FEV<span class="elsevierStyleInf">1</span> &#8805;50&#37; and &#60;80&#37;&#59; severe &#40;stage <span class="elsevierStyleSmallCaps">III</span>&#41; FEV<span class="elsevierStyleInf">1</span> &#8805;30&#37; and &#60;50&#37;&#59; and very severe &#40;stage <span class="elsevierStyleSmallCaps">IV</span>&#41; FEV<span class="elsevierStyleInf">1</span> &#60;30&#37;&#46; The 2017 GOLD guidelines added a letter &#40;A&#44; B&#44; C&#44; or D&#41; to stages <span class="elsevierStyleSmallCaps">I&#8211;IV</span>&#44; which provides information on the patient&#39;s symptoms and risk of exacerbation&#46; Group A and B patients suffer &#60;2 exacerbations&#47;year without hospitalization&#44; while the groups C and D represent patients with 2 or more exacerbations&#47;year&#44; at least 1 hospitalization or both&#46; Additionally&#44; groups A and C correspond to patients with a dyspnea score of 0&#8211;1 &#40;evaluated with the modified dyspnea scale of the Medical Research Council &#91;mMRC&#93;&#41; and&#47;or scored &#60;10 in the COPD Assessment Test &#40;CAT&#41;&#46; Groups B and D include patients with an mMRC &#8805;2&#44; a CAT score &#8805;10 or both&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Incident cases of cancer and their date of diagnosis during the study period were categorized for subsequent analysis into pulmonary and extrapulmonary cancer&#46; Skin cancer other than melanoma was excluded&#46; Cancer diagnosis was performed by the specialists from the hospital&#46; Deaths in the cohort during the study period &#40;January 2012 to December 2015&#41; were counted&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">An initial descriptive analysis was conducted using mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; for the numerical variables and percentages &#40;&#37;&#41; for the qualitative ones&#46; For point estimates and the 95&#37; confidence intervals &#40;95&#37; CI&#41; of the cancer incidence rate&#44; we used the follow-up period of each patient in months as the denominator&#44; divided by the person-time index until the cancer diagnosis event or the completion of the follow-up period&#46; We calculated overall as well as group-specific rates &#40;pulmonary and extrapulmonary cancer&#41;&#46; Bivariate analysis of the cancer incidence according to patients characteristics as to the computerized medical history employed Chi-squared&#44; Student&#39;s t&#44; or ANOVA test&#44; based on the nature of the variable &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Multivariate analysis was performed using multiple logistic regression &#40;conditional mode&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">For the prospective assessment of the disease-free time &#40;in years&#41; to cancer diagnosis or the end of follow-up in December 2015&#44; we employed a survival analysis&#44; expressing the &#8220;cumulative disease-free percentage&#8221; as survival&#46; The event to measure was the diagnosis of cancer &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; We used Cox regression for multivariate adjustment and the log rank test for comparing the GOLD categories regrouped in dichotomous format &#40;<span class="elsevierStyleSmallCaps">I<span class="elsevierStyleMonospace">-</span>II</span>vs&#46; <span class="elsevierStyleSmallCaps">III&#8211;IV</span>&#41;&#44; as these groups better discriminated differences between &#8220;cumulative disease-free percentages&#8221;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">All hypothesis tests were bilateral&#44; for a significance level of 5&#37;&#46; The analyses were performed using the statistical SPSS&#47;PC program &#40;version 21&#46;0 for Windows&#59; SPSS Inc&#46;&#44; Chicago&#44; IL&#41;&#46; The study was approved by the Ethics Committee of the HUNSC&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">We included 308 patients with COPD&#59; 33 patients died&#44; and 48 were diagnosed with cancer during the study period&#46; The incidence rate was therefore 10&#46;3 cases per 1000 COPD cases per year &#40;95&#37; CI 7&#46;6&#8211;13&#46;6 cases&#41;&#46; The most frequent tumors were lung tumors &#40;31&#37;&#41;&#44; genitourinary tract tumors &#40;29&#37;&#41;&#44; gastrointestinal tumors &#40;21&#37;&#41;&#44; head&#47;neck tumors &#40;6&#37;&#41; and miscellaneous &#40;12&#46;5&#37;&#41;&#46; In terms of location&#44; the annual incidence rate for lung cancer was 3&#46;4 cases per 1000 COPD cases per year &#40;95&#37; CI 1&#46;9&#8211;5&#46;6 cases&#41;&#46; For extrapulmonary tumors&#44; the rate was 7&#46;3 cases per 1000 COPD cases per year &#40;95&#37; CI 5&#8211;10 cases&#41;&#46; These values reflect an incidence rate of 2&#46;14 &#40;95&#37; CI 1&#46;16&#8211;3&#46;94&#41; in favor of malignancies of extrapulmonary origin &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;017&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical and demographic characteristics of the series and the contrasts of the cross-sectional bivariate analysis are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Cancer diagnoses were more frequent in patients with a higher PYI&#44; but we did not detect significant differences in the other variables&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In the multivariate logistic regression analysis&#44; we observed a significant increase in the mean risk of cancer in patients with mild to moderate obstruction&#44; grouped according to the 2009 GOLD classification &#40;grades <span class="elsevierStyleSmallCaps">I</span> and <span class="elsevierStyleSmallCaps">II</span>&#41;&#44; compared to patients with more severe obstructions &#40;grades III and IV&#41;&#44; as well as in those with a higher accumulated tobacco consumption&#44; when the rest of the variables were excluded from the equation&#46; The adjusted odds ratio &#40;OR&#41; is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A&#46; The prospective assessment of cancer incidence &#40;longitudinal analysis&#44; Cox regression&#41; reinforced these associations by also showing a significant difference in the cumulative cancer-free probability&#58; the patient group with mild to moderate obstruction and the one with a higher PYI had a higher cancer incidence rate &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>B&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">In this patient cohort diagnosed with COPD&#44; the incidence rate of cancer at any site was 10&#46;3 cases per 1000 patients with COPD per year&#46; The incidence rate for extrapulmonary malignancies doubled that for primary pulmonary malignancies&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The association between lung cancer and COPD has been clearly established&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">15&#8211;29</span></a> The high prevalence of lung cancer in COPD suggests that there are common mechanisms in both diseases&#46; These mechanisms include genetic&#44; epigenetic and inflammatory factors and the structural lung impairment in COPD&#44; which promotes the development of malignancies&#44; beyond the adverse effect of tobacco smoke itself&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">17&#44;38&#44;40</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The incidence rate of lung cancer in patients with COPD ranges from 1&#46;4 to 16&#46;7 per 1000<span class="elsevierStyleHsp" style=""></span>person-years&#44;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">19&#44;22&#44;40</span></a> with our results agreeing with those published in the Lung Health Study&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">19</span></a> Comparing our series with similar studies in the Spanish population&#44; our incidence rate was lower than that described by Torres et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">22</span></a> which could reflect the increased tobacco consumption &#40;mean PYI of 74&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;9&#41; reported in the former study&#46; The Cancer Prevention Study II<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">43</span></a> showed that smoking a pack of cigarettes per day for 30 years increased the specific mortality due to lung cancer by 20&#8211;40&#37; in men and 14&#8211;20&#37; in women&#44; compared with individuals who had never smoked&#46; The risk virtually doubled if the consumption was maintained for more than 40 years&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">44</span></a> Doll and Peto<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">45</span></a> developed a quantitative model for lung cancer risk&#44; in which the duration of smoking was more significant than the number of cigarettes smoked&#44; in individuals with a comparable packs-per-year consumption&#46; In this model&#44; the association between the number of cigarettes smoked per day and the risk of lung cancer was relatively linear&#46; However&#44; the duration of tobacco consumption was related to an exponential increase in the risk of lung cancer&#46; In line with these data&#44; an association between the PYI and the development of mutations in various target organs has been found&#44; which seems to promote not only the development of lung cancer but also extrapulmonary tumors in the bladder&#44; colon and larynx&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">7</span></a> These results are in accordance with our findings&#44; insofar as the overall incidence of cancer was higher in those patients with COPD who had a higher PYI&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In our study&#44; there was a notably high incidence of extrapulmonary tumors&#44; especially in patients with COPD and mild to moderate airflow obstruction&#46; Nakayama et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">30</span></a> investigated the development of cancer in 127 patients with COPD compared to patients with no obstruction who smoked&#46; The patients with COPD had a relative cancer risk of 2&#46;2 &#40;95&#37; CI 1&#46;24&#8211;4&#46;27&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0069&#41; compared with control subjects&#46; The most frequent tumors were lung&#44; head and neck and urinary tract tumors&#46; Purdue et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a> assessed the risk of cancer in construction workers diagnosed with COPD and found an increase of 2&#46;2 &#40;95&#37; CI 1&#46;8&#8211;2&#46;7&#41; in the risk of lung cancer and 1&#46;6 &#40;95&#37; CI 1&#46;4&#8211;2&#46;0&#41; in the risk of extrapulmonary cancer&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Chiang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">32</span></a> demonstrated that patients with COPD have a higher risk of developing certain tumors&#44; such as head and neck&#44; esophageal&#44; lung&#44; breast&#44; prostate&#44; central nervous system&#44; lymphoma and multiple myeloma tumors&#46; In our cohort&#44; the most frequent extrapulmonary malignancies were colorectal and prostate cancer&#46; Although their incidence rates in the general population increase from the age of 50 years of age&#44; which could bias the results given the mean age of our series&#44; various studies have shown that these tumors occur more frequently in patients with COPD than in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">32&#8211;34</span></a> Patients with COPD have a higher risk of prostate cancer &#40;hazard ratio&#44; 4&#46;9&#59; 95&#37; CI 1&#46;8&#8211;13&#46;5&#41; than patients without bronchial obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a> Although testosterone levels are reduced in COPD patients&#44; a relation with the development of prostate cancer has not been established&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">34&#44;46</span></a> A number of factors such as obesity&#44; physical inactivity&#8212;circumstances commonly present in patients with COPD&#8212;and the type of diet appear to be common elements the development of colorectal and lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">17&#44;47&#44;48</span></a> Chun et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">35</span></a>found that patients with COPD had a greater risk of colorectal polyps than patients without obstruction &#40;OR&#44; 2&#46;1&#59; 95&#37; CI 1&#46;1&#8211;3&#46;8&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;019&#41;&#46; The authors therefore recommended periodic colonoscopies for these patients to detect premalignant lesions&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In our analysis&#44; the incidence of extrapulmonary cancer doubled that of lung cancer&#44; with a notable percentage of patients who developed colorectal&#44; prostate and bladder cancer&#46; A reasonable explanation&#44; beyond the damage generated by the carcinogenic substances in tobacco&#44; could be the presence of low-grade COPD-associated systemic inflammation&#46; A number of key compounds in the pathogenic process are known to link inflammation with carcinogenesis&#44; such as integrins&#44; transforming growth factor beta&#44; NF-kappa beta transcription factor&#44; the signal transducer and activator of transcription 3&#44; tumor necrosis factor alpha and cyclooxygenase-2&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">36&#8211;39</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">It is notable that patients who are more susceptible to developing cancer were those with milder stages of the disease&#46; This fact could be due to a survival bias&#44; where patients with more severe COPD&#44; who could lack the predisposing factors for developing cancer&#44; thereby reach more advanced phases of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">49</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">This study had some limitations&#46; Firstly&#44; the study population came from a single hospital&#44; and the sample size was limited&#46; Obviously&#44; a larger sample could have revealed differences undetected in the current analysis&#46; Recruiting a larger&#44; representative sample of patients with COPD throughout the Canary Islands would undoubtedly be of interest&#46; Secondly&#44; a potential information bias could have occurred from obtaining the variables from the patients&#8217; medical history&#44; although the current standardization of diagnostic criteria minimizes this possibility&#46; Thirdly&#44; we did not have a control group from the general population or smokers without obstruction&#46; Therefore&#44; we cannot rule out some factor that could explain the high number of extrapulmonary malignancies in the cohort&#46; Lastly&#44; we should consider the inherent limitations of a nonpopulational-based study&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion&#44; patients with COPD and a mild to moderate degree of airflow obstruction &#40;grades I and II of the 2009 GOLD guidelines&#41; have a greater risk of developing cancer at various sites compared with those with a more advanced obstruction&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The relationship between chronic obstructive pulmonary disease &#40;COPD&#41; and the overall incidence of cancer is poorly understood&#46; The aim of this study was to analyze the incidence of cancer &#40;pulmonary and extrapulmonary sites&#41; in patients with COPD followed up in a specialized outpatient unit&#44; and to assess the relationship to the degree of airflow obstruction&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective observational study was conducted with a cohort of 308 patients with COPD followed up at pulmonology outpatient clinics from January 2012 to December 2015&#46; The neoplasms diagnosed during this period were divided into a pulmonary and an extrapulmonary group&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The overall yearly incidence rates of cancer&#44; lung cancer and extrapulmonary cancer cases per 1000 patients with COPD were 10&#46;3&#44; 3&#46;4 and 7&#46;3 cases&#44; respectively&#46; The most frequent cancer types were lung cancer &#40;31&#37;&#41;&#44; genitourinary tract cancer &#40;29&#37;&#41; and gastrointestinal cancer &#40;21&#37;&#41;&#46; Mild to moderate stages &#40;grade I&#8211;II of the 2009 GOLD classification&#41; and the increase in the pack-year index &#40;PYI&#41; were related to an increase in the onset of neoplasia&#44; with an odds ratio &#40;OR&#41; of 2&#46;16 &#40;95&#37; confidence interval &#91;95&#37; CI&#93;&#58; 1&#46;087&#8211;4&#46;309&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;026&#41; and 1&#46;01 &#40;95&#37; CI&#58; 1&#46;002&#8211;1&#46;031&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;023&#41;&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The incidence of extrapulmonary cancer in patients with COPD was twice that of lung cancer&#59; stages <span class="elsevierStyleSmallCaps">I&#8211;II</span> of the 2009 GOLD classification and the PYI were significantly related to the onset of neoplasia&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methodology"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La relaci&#243;n entre la enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41; y la incidencia global de c&#225;ncer es poco conocida&#46; El objetivo del estudio fue analizar la incidencia de c&#225;ncer &#40;tanto de localizaci&#243;n pulmonar como extrapulmonar&#41; en pacientes con EPOC en seguimiento en una consulta ambulatoria especializada&#44; as&#237; como valorar su relaci&#243;n con el grado de obstrucci&#243;n al flujo a&#233;reo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodolog&#237;a</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional prospectivo de una cohorte de 308 pacientes con EPOC en seguimiento en consultas ambulatorias de neumolog&#237;a durante el periodo comprendido entre enero de 2012 y diciembre de 2015&#46; Las neoplasias diagnosticadas en este periodo se dividieron en pulmonares y extrapulmonares&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Las tasas de incidencia global de c&#225;ncer&#44; de c&#225;ncer de pulm&#243;n &#40;CP&#41; y de c&#225;ncer extrapulmonar fueron de 10&#44;3&#44; 3&#44;4 y 7&#44;3 casos por 1&#46;000 pacientes EPOC-a&#241;o&#44; respectivamente&#46; Los tumores m&#225;s frecuentes fueron el CP &#40;31&#37;&#41;&#44; los del tracto genitourinario &#40;29&#37;&#41; y digestivo &#40;21&#37;&#41;&#46; Los estadios leve-moderado &#40;grados<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">I</span>-<span class="elsevierStyleSmallCaps">II</span> de la GOLD 2009&#41; y el incremento del &#237;ndice paquetes-a&#241;o &#40;IPA&#41; se relacionaron con un aumento en la aparici&#243;n de neoplasias con un odds ratio &#40;OR&#41; de 2&#44;16 &#40;intervalo de confianza al 95&#37; &#91;IC<span class="elsevierStyleInf">95&#37;&#93;</span>&#58; 1&#44;087-4&#44;309&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&#41; y 1&#44;01 &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58;1&#44;002-1&#44;031&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41;&#44; respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La incidencia de c&#225;ncer de localizaci&#243;n extrapulmonar en pacientes con EPOC duplica a la de CP&#46; Los estadios<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">I</span>-<span class="elsevierStyleSmallCaps">II</span> de la GOLD 2009 y el IPA se relacionan de forma significativa con la aparici&#243;n de neoplasias&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Metodolog&#237;a"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Figueira Gon&#231;alves JM&#44; Dorta S&#225;nchez R&#44; P&#233;rez M&#233;ndez LI&#44; P&#233;rez Negr&#237;n L&#44; Garc&#237;a-Talavera I&#44; P&#233;rez Rodr&#237;guez A&#44; et al&#46; Incidencia de c&#225;ncer en pacientes ambulatorios con enfermedad pulmonar obstructiva cr&#243;nica&#46; Rev Clin Esp&#46; 2017&#59;217&#58;387&#8211;393&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">This manuscript won the 2016 Respiratory Disease Prize of the Royal Academy of Medicine of Santa Cruz de Tenerife&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1254
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cumulative probability of being cancer free for patients with chronic obstructive pulmonary disease&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#42;Age of the patient with chronic obstructive pulmonary disease at the time of cancer diagnosis&#46; Dashed line&#58; GOLD III&#8211;IV&#46; Continuous line&#58; GOLD I&#8211;II<span class="elsevierStyleSmallCaps">&#46;</span> Log rank test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;072&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; COPD&#44; chronic obstructive pulmonary disease&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BMI&#44; body mass index &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#59; FEV<span class="elsevierStyleInf">1</span>&#44; forced expiratory volume in one second&#59; FVC&#44; forced vital capacity&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease&#59; PYI&#44; pack-year index&#59; SD&#44; standard deviation&#46;</p>"
          "tablatextoimagen" => array:2 [
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                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-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Overall <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>308&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Neoplasia</th><th class="td" title="table-head  " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">No<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>260&nbsp;\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">Yes<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age&#44; years &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;083&nbsp;\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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Sex</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;651&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Female &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">BMI &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;846&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">BMI</span> &#8805;30 <span class="elsevierStyleItalic">&#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;402&nbsp;\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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Smoking</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;070&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ex-smoker &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Active smoker &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PYI <span class="elsevierStyleItalic">&#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;047&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PYI &#8805;<span class="elsevierStyleItalic">60 &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;275&nbsp;\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">Pulmonary function</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;302&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&#47;FVC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;455&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;831&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;494&nbsp;\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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">GOLD 2009</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>I&#46; Mild &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>II&#46; Moderate &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>III&#46; Severe &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IV&#46; Very severe &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1525515.png"
              ]
            ]
            1 => 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">&nbsp;\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">A&nbsp;\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">B&nbsp;\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">C&nbsp;\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">D&nbsp;\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">A&nbsp;\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">B&nbsp;\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">C&nbsp;\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">D&nbsp;\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">A&nbsp;\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">B&nbsp;\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">C&nbsp;\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">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">GOLD 2017</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;652&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>I &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>II &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>III &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;6&nbsp;\t\t\t\t\t\t\n
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