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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic obstructive pulmonary disease &#40;COPD&#41; is the fourth leading cause of death worldwide and it is expected to become the third by 2020&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">1</span></a> In Latin American countries&#44; the prevalence of COPD is 13&#46;4&#37; and its in-hospital mortality rate ranges from 6&#46;7&#37; to 29&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">2</span></a> In Chile&#44; respiratory diseases are the third cause of death and&#44; amongst them&#44; COPD accounts for 22&#37;&#44; being the second cause of decease&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">COPD is a complex disease where genetic variants&#44; environmental factors and random events interact to trigger pathological pathways&#46; Genetic susceptibility is evident in familial clustering&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">4</span></a> Specifically&#44; population-based studies on families with respiratory disease have provided evidence for familial aggregation of spirometric parameters&#44; and the heritability of lung function measures have been estimated to range from 10&#37; to 80&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">5&#44;6</span></a> Large genome-wide analysis studies &#40;GWAS&#41; have increased our knowledge about the genetic risk factors for lung function impairment and COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">7</span></a> However&#44; most association studies trying to explain the genetic basis of COPD have been developed in Caucasian and Asian populations&#44; showing some controversial results depending on the population analyzed&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a> So far&#44; only four GWAS assessing lung function or COPD-related phenotypes have been focused on Hispanic&#47;Latino populations&#44; reporting both some novel loci &#40;in or near the genes <span class="elsevierStyleItalic">KLHL7</span>&#47;<span class="elsevierStyleItalic">NUPL2</span>&#44; <span class="elsevierStyleItalic">DLG2</span>&#44; <span class="elsevierStyleItalic">PDZD2</span> and <span class="elsevierStyleItalic">PRDM15</span>&#41; and others previously identified in non-Hispanic samples&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">9&#8211;12</span></a> Moreover&#44; single nucleotide polymorphisms &#40;SNPs&#41; identified through GWAS only explain a small percentage of the heritability of lung function parameters&#44; such as forced expiratory volume in one second &#40;FEV<span class="elsevierStyleInf">1</span>&#44; 9&#46;6&#37;&#41;&#44; forced vital capacity &#40;FVC&#44; 6&#46;4&#37;&#41; and FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio &#40;14&#46;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although the molecular mechanisms of COPD pathogenesis are still unclear&#44; mounting evidence supports that autoimmunity could play a role&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">14&#44;15</span></a> Hence&#44; the presence of autoimmunity-related responses elicited by T-helper type 1 &#40;Th1&#41; and Th17 cells have been reported in COPD patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">16&#44;17</span></a> whereas abnormal levels of pulmonary and circulating autoantibodies have also been associated to COPD&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">18&#44;19</span></a> Also&#44; the results of some genetic studies have suggested a contribution of autoimmune responses to the development of COPD&#46; For instance&#44; Wain LV and colleagues have reported an association between decreased FEV<span class="elsevierStyleInf">1</span> and the HLA-DQB1&#47;HLA-DQA2 region&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">20</span></a> In turn&#44; a recent GWAS using samples from 18&#46;335 Caucasian adults have identified a positive association of rs2074488&#44; a SNP linked to the HLA-C gene&#44; and COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">21</span></a> Since human leukocyte antigens &#40;HLA&#41; alleles have been repeatedly associated with auto-immune diseases&#44;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">22&#44;23</span></a> these results reinforce the idea of an autoimmune component in COPD&#46; Notwithstanding&#44; the relation between HLA and COPD remains largely obscure&#44; especially in Latin American &#40;LA&#41; populations&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">To overcome this limitation&#44; the present study aimed to analyze the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">We studied 214 COPD patients recruited at the Respiratory Service of the Hospital Regional de Talca&#44; Chile&#44; where they attended to undergo diagnostic tests after suspected COPD or for COPD monitoring visits&#46; In parallel&#44; 193 age-matched healthy controls were recruited at the same Hospital through a volunteer recruitment program&#46; In order to rule out patients with asthma-COPD overlap syndrome&#44; subjects with a history of asthma&#44; rhinitis or any extra-pulmonary disease affecting lung function&#44; and with positive bronchodilator test&#44; FEV<span class="elsevierStyleInf">1</span> increasing by &#8805;12&#37; and 200<span class="elsevierStyleHsp" style=""></span>ml&#44; were excluded from the study&#46; In addition&#44; 510 unrelated volunteers were randomly recruited among blood donors between January 2015 and May 2018 at Casa del Donante&#44; Talca&#44; Chile to reexamine the distribution of HLA-DRB1 alleles&#46; 160 out of these 510 were submitted to HLA-A&#44; -B and -C typing&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">24</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Diagnostic evaluation of subjects was performed using GOLD criteria<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">1</span></a> and medical history was considered standardizing clinical information&#46; Pulmonary function &#8211; including measurements of FEV<span class="elsevierStyleInf">1</span>&#44; FVC and carbon monoxide diffusing capacity of the lung &#40;DL<span class="elsevierStyleInf">CO</span>&#41; &#8211; was assessed in all subjects using standard procedures<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">25</span></a> and equipment &#40;Masterlab&#59; Jaeger&#44; W&#252;rzburg&#44; Germany&#41;&#46; Also&#44; oxygen saturation was measured by pulse-oximetry &#40;Ohmeda TuffSat&#44; Soma Technology&#44; Connecticut&#44; USA&#41;&#46; Body Mass Index &#40;BMI&#41; was calculated by dividing each person&#39;s weight in kilograms into their height in squared meters&#46; Exercise capacity was determined with the distance walked in 6<span class="elsevierStyleHsp" style=""></span>minutes test &#40;6MWT&#41;&#46; The amount of cigarette smoking history was measured by pack-years and cumulative exposure to biomass smoke was calculated and expressed as hour-years as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Genotyping and imputation</span><p id="par0035" class="elsevierStylePara elsevierViewall">Genotyping was performed using the Illumina Infinium Global Screening Array &#40;Illumina&#44; California&#44; USA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">12</span></a> The classic HLA alleles at HLA-A&#44; B&#44; C&#44; DPB1&#44; DQA1&#44; DQB1&#44; and DRB1 were imputed using HLA Genotype Imputation with Attribute Bagging &#40;HIBAG&#41; with the Hispanic reference data set&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analyses</span><p id="par0040" class="elsevierStylePara elsevierViewall">Clinic and demographical data were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; Comparisons between COPD patients and subjects were performed using the Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#46; SNPs that met the quality criteria of a minor allele frequency &#40;MAF&#41;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#44; missingness<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#44; and&#47;or Hardy&#8211;Weinberg equilibrium &#40;HWE&#41; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;001 were included in the association analyses&#46; A total of 7257 SNPs was located on chromosome 6 &#40;chr6&#58; 28400538&#8211;33489882&#44; hg19&#41; &#40;genotyping rate&#58; 0&#46;93&#41;&#46; For single-variant association analysis&#44; we used PLINK &#40;v1&#46;9&#41; to perform logistic regression for binary phenotype &#40;COPD and healthy controls&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">28</span></a> HLA association analysis was performed with the PyHLA software<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">29</span></a> and R version 3&#46;4&#46;0&#46; &#40;<a href="https://cran.r-project.org/">https&#58;&#47;&#47;cran&#46;r-project&#46;org&#47;</a>&#41;&#44; using additive logistic regression models&#46; Age&#44; sex&#44; and the first two principal components of a PCA based on genetic data&#44; were used as covariates in all tests&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical and demographical findings</span><p id="par0045" class="elsevierStylePara elsevierViewall">COPD patients and controls were similar with regard to age&#44; while smoking pack-years and biomass exposure were significantly higher in COPD patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; As expected&#44; lung function parameters were significantly reduced in COPD patients&#44; as well as oxygen saturation and 6MWT&#46; Control subjects exhibited a significantly higher BMI than COPD patients and&#44; interestingly&#44; both groups showed overweight &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#46;0 to &#60;30&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Genetic association between HLA-alleles and COPD</span><p id="par0050" class="elsevierStylePara elsevierViewall">Of the 7257 SNPs genotyped&#44; in the HLA region&#44; ten markers showed suggestive associations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; Supplementary Files 1&#41;&#46; After HLA imputation&#44; four HLA alleles showed a trend to association with COPD &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46; HLA-DRB1&#42;15&#58;01 was decreased in patients with COPD compared to healthy controls&#44; although no significant difference was observed &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;59&#44; 95&#37; CI 0&#46;34&#8211;1&#46;02&#41;&#46; By contrast&#44; the frequencies of HLA-B&#42;35&#58;01 and HLA-C&#42;04&#58;01 alleles were increased in COPD compared to controls &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;73&#44; 95&#37; CI 1&#46;07&#8211;2&#46;78&#59; and OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;49&#44; 95&#37; CI 1&#46;01&#8211;2&#46;21&#59; respectively&#41;&#46; The interaction test revealed that B&#42;35&#58;01 and C&#42;04&#58;01 were in LD in both COPD and controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;61<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;36</span> and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#46;67<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;23</span>&#44; respectively&#41;&#46; Finally&#44; we included in the analysis the HLA-A&#44; -B&#44; -C and -DRB1 typing performed in the Chilean population previously described by our group&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">24</span></a> No differences were observed in the distribution of HLA-B&#42;35&#58;01 and HLA-C&#42;04&#58;01 alleles among control subjects and patients with COPD &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; On the contrary&#44; the HLA-DRB1&#42;01&#58;02 allele frequency was increased in patients with COPD when compared with healthy controls &#40;6&#46;54&#37; vs&#46; 3&#46;27&#37;&#44; <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;07&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Genetic association between HLA-alleles and clinical parameters</span><p id="par0055" class="elsevierStylePara elsevierViewall">We also analyzed the possible influence of HLA class I and II alleles in pulmonary function&#44; exercise capacity and oxygen saturation&#44; in COPD patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#59; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; HLA-DRB1&#42;01&#58;02 was significantly associated with FEV<span class="elsevierStyleInf">1</span> and oxygen saturation &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#59; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and B&#41;&#46; Moreover&#44; FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio was higher among HLA-DRB1&#42;15&#58;01-positive patients compared with HLA-DRB1&#42;15&#58;01-negative patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#46; Regarding exercise capacity&#44; we observed that the median 6MWT value in the group of HLA-DRB1&#42;14&#58;02-negative patients was higher as compared with the HLA-DRB1&#42;14&#58;02-positive patient group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The present study aimed to investigate the association of HLA class I and II alleles and COPD in the Chilean population&#44; characterized by a large admixture ancestry&#46; We show for the first time that HLA-DRB1&#42;01&#58;02 allele frequency is significantly increased in patients with COPD compared with healthy controls&#46; Moreover&#44; some HLA-DRB1 alleles correlated with clinical and pulmonary function parameters in COPD&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The HLA region plays a crucial role in numerous pathologies&#44; as it accounts for 25&#37; of known associations from the GWAS catalog &#40;<a href="https://www.ebi.ac.uk/gwas/">https&#58;&#47;&#47;www&#46;ebi&#46;ac&#46;uk&#47;gwas&#47;</a>&#41;&#44; especially with immune-related diseases&#46; However&#44; the relationship between HLA and COPD is unclear&#44; since available data on this subject is scarce&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">30</span></a> In this regard&#44; a previous study reported that the presence of alanine at amino acid position 57 &#40;instead of aspartic acid&#44; valine or serine&#41; in HLA-DQ&#946;1 was associated with decreased lung function&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">13</span></a> In turn&#44; Faner and co-workers reported a higher prevalence of DRB1&#42;14 in patients with severe airflow limitation and low DL<span class="elsevierStyleInf">CO</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">31</span></a> Likewise&#44; here we report associations of HLA-DRB1 alleles with pulmonary function &#40;HLA-DRB1&#42;01&#58;02 and HLA-DRB1&#42;15&#58;01&#41;&#44; exercise capacity &#40;HLA-DRB1&#42;14&#58;02&#41; and oxygen saturation &#40;HLA-DRB1&#42;01&#58;02&#41;&#44; in COPD patients&#46; Indeed&#44; the HLA-DRB1 is the most polymorphic gene within the HLA-II region&#44; and it has been frequently associated with autoimmune diseases such as rheumatoid arthritis &#40;RA&#41;&#44; spondylarthritis&#44; systemic lupus erythematosus and multiple sclerosis&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">32</span></a> Moreover&#44; a meta-analysis performed in Latin American patients with different autoimmune-diseases revealed that specific HLA-DRB1 polymorphisms are shared between more than one of these conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">33</span></a> Interestingly&#44; it has been hypothesized that polymorphisms in HLA-II region could lead to the loss of immunological tolerance to self-antigens&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">34</span></a> In this regard&#44; substantial evidence has shown the presence of self-antigens and autoantibodies in COPD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">18&#44;35&#44;36</span></a> Hence&#44; the HLA-DRB1 alleles showing association with COPD risk and lung function parameters could be involved in this auto-immune mechanism&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">It is noteworthy that HLA-DRB1 shared epitope &#40;SE&#41; alleles &#40;which encode a common amino acid sequence&#41;&#44; are the most important genetic contributors for the risk of developing anti-citrullinated protein autoantibodies &#40;ACPA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">37</span></a> ACPA are different isotype autoantibodies that recognize the nonessential amino acid citrulline in proteins&#46; Their presence has an important role in RA prognosis&#44; since it is associated to severity of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">37</span></a> In this regard&#44; it has been suggested that lungs may be initiating sites of the generation of ACPA&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">38</span></a> Although COPD is not a primary RA-related lung disease&#44; a high prevalence of ACPA in COPD patients has been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">39</span></a> Moreover&#44; it has also been reported that heavy smokers with COPD are more prone to ACPA production compared with heavy smokers without COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">38</span></a> Hence&#44; higher ACPA levels could increase the risk to develop COPD&#44; even in the absence of RA&#46; Indeed&#44; citrullinated proteins are increased in patients with COPD and correlate with ongoing inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">40</span></a> Furthermore&#44; it has been shown that anti-cyclic citrullinated peptide antibodies levels are higher in COPD patients exposed to biomass smoke&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">41</span></a> Although ACPA determination was not performed in our cohort&#44; COPD patients exhibited a substantial exposure to biomass smoke&#46; In this frame&#44; it is conceivably that HLA-DRB1 alleles could contribute to ACPA generation as a result of immunization to newly synthesized citrullinated peptides&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">On the other hand&#44; we acknowledge some limitations&#44; being the relatively small sample size and limited statistical power the most important&#46; Hence&#44; the associations found between COPD risk and HLA-B&#42;35&#58;01 and HLA-C&#42;04&#58;01 alleles disappeared when study population was increased&#46; Moreover&#44; the imputation of HLA alleles in LA populations may be controversial due to the scant information available and the complexity of the admixture&#46; The fact that the number of males in the control group almost doubled that of the patients group could have also biased our results&#44; since biological and behavioral&#47;environmental gender differences have been recognized to influence COPD development&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">42</span></a> On the other hand&#44; although we did not collect self-reported ethnicity&#44; it has been shown that population from El Maule Region has a global ancestry estimate of 42&#46;41&#37; Native American&#44; 55&#46;62&#37; European and 1&#46;97&#37; African&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">43</span></a> This is adds relevance to our analysis&#44; since it is accepted that studies in admixed-ancestry populations could yield disease-associated loci that may have been missed due to allele frequencies disparities&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">12</span></a> Moreover&#44; our findings are consistent with a plausible auto-immune process in COPD pathogenesis&#44; which has been long recognized as a potential mechanism&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In conclusion&#44; the present study shows an association among HLA-DRB1 alleles&#44; COPD risk and COPD-related clinical parameters in an admixed LA population&#46; Given that HLA-DRB1 gene is related to autoimmunity&#44; our study supports the notion of an autoimmune process in the pathogenesis of COPD and justifies the need to develop more research on the association between HLA alleles and COPD risk&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Statement of ethics</span><p id="par0085" class="elsevierStylePara elsevierViewall">This research complies with the guidelines for human studies and was conducted ethically in accordance with the World Medical Association Declaration of Helsinki&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Authors&#8217; contributions</span><p id="par0090" class="elsevierStylePara elsevierViewall">Study concept and design&#58; JO&#44; RDP&#59; Data acquisition&#58; RSS&#44; SJ&#44; JO&#59; Data analysis&#58; JO&#44; RDP&#44; HDH&#59; Data interpretation&#58; JO&#44; RDP&#44; MM&#59; Funding acquisition&#58; JO&#44; RSS&#59; Investigation&#58; JO&#44; RDP&#59; Methodology&#58; JO&#44; RDP&#59; Supervision&#58; JO&#59; Writing &#8211; original draft&#58; JO&#44; RDP&#59; Writing &#8211; review &#38; editing&#58; JO&#44; RDP&#44; HDH&#44; RSS&#44; SJ&#44; MM&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding sources</span><p id="par0095" class="elsevierStylePara elsevierViewall">Funding support for this study was provided by the <span class="elsevierStyleGrantSponsor" id="gs1">Chilean National Science and Technology Fund &#40;CONICYT&#41;</span>&#44; FONDECYT Project N&#176; 11150022&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">Marc Miravitlles has received speaker fees from AstraZeneca&#44; Boehringer Ingelheim&#44; Chiesi&#44; Cipla&#44; Menarini&#44; Rovi&#44; Bial&#44; Sandoz&#44; Zambon&#44; CSL Behring&#44; Grifols and Novartis&#44; consulting fees from AstraZeneca&#44; Boehringer Ingelheim&#44; Chiesi&#44; GlaxoSmithKline&#44; Bial&#44; Gebro Pharma&#44; CSL Behring&#44; Laboratorios Esteve&#44; Ferrer&#44; Mereo Biopharma&#44; Verona Pharma&#44; TEVA&#44; pH Pharma&#44; Novartis and Grifols and research grants from GlaxoSmithKline and Grifols&#44; all outside the submitted work&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The rest of the authors declare no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">While the molecular mechanisms of COPD pathogenesis remain obscure&#44; there is mounting evidence supporting a key role for autoimmunity&#46; Although human leukocyte antigens &#40;HLA&#41; alleles have been repeatedly associated with autoimmune processes&#44; the relation between HLA and COPD remains largely unexplored&#44; especially in Latin American &#40;LA&#41; populations&#46; Consequently&#44; this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">COPD patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>214&#41; and age-matched controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>193&#41; were genotyped using the Illumina Infinium Global Screening Array&#46; The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging &#40;HIBAG&#41; and the Hispanic reference panel&#46; Finally&#44; the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">CODP patients showed a higher HLA-DRB1&#42;01&#58;02 allele frequency &#40;6&#46;54&#37;&#41; than healthy controls &#40;3&#46;27&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#44; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;07&#41;&#46; HLA-DRB1&#42;01&#58;02 was also significantly associated with FEV<span class="elsevierStyleInf">1</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; and oxygen saturation &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; and the FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio was higher in HLA-DRB1&#42;15&#58;01-positive patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">We report an association among HLA-DRB1 alleles&#44; COPD risk and pulmonary function parameters for the first time in Latin Americans&#46; Since HLA-DRB1 genetic variability relates to the individual autoimmune response&#44; these results support a role of autoimmunity in the pathogenesis of COPD&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
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            "identificador" => "abst0025"
            "titulo" => "Conclusion"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Si bien los mecanismos moleculares de la patog&#233;nesis de la EPOC siguen sin ser claramente conocidos&#44; cada vez existe m&#225;s informaci&#243;n que respalda que la autoinmunidad tiene un papel clave&#46; Aunque los alelos de los ant&#237;genos leucocitarios humanos &#40;HLA&#41; se han asociado repetidamente con procesos autoinmunes&#44; la relaci&#243;n entre los HLA y la EPOC permanece en gran parte inexplorada&#44; especialmente en las poblaciones latinoamericanas &#40;LA&#41;&#46; En consecuencia&#44; este estudio tuvo como objetivo investigar la presencia de los alelos de HLA de clase I y II en pacientes con EPOC y controles sanos en una poblaci&#243;n LA mestiza&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se analiz&#243; el genotipo de pacientes con EPOC &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>214&#41; y controles de la misma edad &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>193&#41; utilizando el Illumina Infinium Global Screening Array&#46; Los alelos cl&#225;sicos de los HLA se imputaron usando la imputaci&#243;n del genotipo HLA con empaquetamiento de atributos &#40;HIBAG&#44; por sus siglas en ingl&#233;s&#41; y el panel de referencia hispano&#46; Finalmente&#44; la distribuci&#243;n de los alelos HLA-DRB1 se reexamin&#243; en 510 voluntarios no emparentados reclutados al azar&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con EPOC mostraron una mayor frecuencia de alelos HLA-DRB1&#42;01&#58;02 &#40;6&#44;54&#37;&#41; que los controles sanos &#40;3&#44;27&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;07&#41;&#46; El HLA-DRB1&#42;01&#58;02 tambi&#233;n se asoci&#243; significativamente con el FEV<span class="elsevierStyleInf">1</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41; y la saturaci&#243;n de ox&#237;geno &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41;&#44; y la relaci&#243;n FEV<span class="elsevierStyleInf">1</span>&#47;FVC fue mayor en los pacientes con HLA-DRB1&#42;15&#58;01 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">-3</span>&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusi&#243;n</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comunicamos una asociaci&#243;n entre los alelos HLA-DRB1&#44; el riesgo de la EPOC y los par&#225;metros de la funci&#243;n pulmonar por primera vez en latinoamericanos&#46; Dado que la variabilidad gen&#233;tica de HLA-DRB1 se relaciona con la respuesta autoinmune individual&#44; estos resultados respaldan el papel de la autoinmunidad en la patog&#233;nesis de la EPOC&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0030"
            "titulo" => "Introducci&#243;n"
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            "identificador" => "abst0035"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Conclusi&#243;n"
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Genetic association between HLA-alleles and clinical parameters in COPD cases&#46; &#40;A and B&#41; HLA-DRB1&#42;01&#58;02 was significantly associated with FEV1 and oxygen saturation &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#59; respectively&#41;&#46; &#40;C&#41; HLA-DRB1&#42;15&#58;01-positive patients exhibited a higher FEV1&#47;FVC ratio than HLA-DRB1&#42;15&#58;01-negative patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41;&#46; &#40;D&#41; HLA-DRB1&#42;14&#58;02-negative patients showed a higher 6MWT value &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Data presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#44; unless otherwise indicated&#46; Definition of abbreviations&#58; FEV<span class="elsevierStyleInf">1</span>&#58; forced expiratory volume in 1 second&#59; FVC&#58; forced vital capacity&#59; DLCO&#58; carbon monoxide diffusing capacity&#59; BMI&#58; body mass index&#59; 6<span class="elsevierStyleHsp" style=""></span>MW&#58; 6<span class="elsevierStyleHsp" style=""></span>minutes walking test&#59; mMRC&#58; modified Medical Research Council scale&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD patients<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>214&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control subjects<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>193&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Sex&#44; male&#47;female&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">121&#47;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#47;133&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">70&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">68&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Smoking history&#44; pack-years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;25<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Biomass exposure&#44; hour-years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">225&#46;62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>54&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">96&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;57<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span>&#44; &#37; predicted&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">61&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">108&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;40<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">58&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">83&#46;00<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;27<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">DL<span class="elsevierStyleInf">CO</span>&#44; &#37; predicted&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">72&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">87&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;48<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">92&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">96&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;34<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">26&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">462&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>87&#46;82<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">mMRC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2562024.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Different from COPD patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical data&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
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          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Only <span class="elsevierStyleItalic">p</span> values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span> are shown&#46; A1&#58; minor allele nucleotide&#59; COPD&#58; chronic obstructive pulmonary disease&#59; MAF&#58; minor allele frequency&#59; SNP&#58; single nucleotide polymorphism&#59; OR&#58; odds ratio&#59; CI&#58; confidence interval&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SNP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Associated Gene&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MAFCOPD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">rs72881217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">33119305&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intergenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">9&#46;43<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;06 &#40;1&#46;33&#8211;3&#46;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs535586&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31860337&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EHMT2 &#40;Synonymous Variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;04<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;52 &#40;0&#46;35&#8211;0&#46;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs75456009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31321551&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HLA-B &#40;Downstream Variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;79<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;66 &#40;1&#46;21&#8211;2&#46;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs521977&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31836827&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLC44A4 &#40;Intron Variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;67<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;52 &#40;0&#46;34&#8211;0&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs4713451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31272581&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LOC107984146 &#40;Intron Variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;35<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;79 &#40;1&#46;21&#8211;2&#46;65&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs3130003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33331061&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intergenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;04&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">SLC44A4 &#40;Intron Variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">C2 &#40;Intron Variant&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">MUC22 &#40;Intron Variant&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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      4 => array:8 [
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        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">OR&#58; odds ratio&#59; CI&#58; confidence interval&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">p</span> values were determined by Fisher&#39;s 2-tailed exact test&#46;</p>"
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                  \t\t\t\t" scope="col">HLA Allele&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthy controls&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>353&#41;</th><th class="td" title="\n
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            1 => array:2 [
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                0 => """
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">HLA Allele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD cases&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>214&#41;</th><th class="td" title="\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthy controls&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>703&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">OR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">95&#37; CI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">DRB1&#42;01&#58;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#46;07&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;04&#8211;4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DRB1&#42;14&#58;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;97&#8211;2&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DRB1&#42;15&#58;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&#46;21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">12&#46;52&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;88&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;55&#8211;1&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2562025.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Frequency distribution of HLA alleles between COPD cases and controls&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
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        "tabla" => array:2 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA-DRB1&#42;01&#58;02Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA-DRB1&#42;01&#58;02Negative &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>201&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA-DRB1&#42;14&#58;02Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA-DRB1&#42;14&#58;02Negative &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>190&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA-DRB1&#42;15&#58;01Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA-DRB1&#42;15&#58;01Negative &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>189&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Smoking history&#44; pack-years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">41&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;32&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">35&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>49&#46;07&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;67<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">37&#46;01<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>49&#46;93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">31&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30&#46;63&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">36&#46;40<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>49&#46;79&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Biomass exposure&#44; hour-years&nbsp;\t\t\t\t\t\t\n
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