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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "305" "paginaFinal" => "310" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Nezihe Özdoğan, Nuri Tutar, Ramazan Demir, Çetin Saatçi, Asiye Kanbay, Hakan Büyükoğlan" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Nezihe" "apellidos" => "Özdoğan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Nuri" "apellidos" => "Tutar" "email" => array:1 [ 0 => "drnuritutar@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Ramazan" "apellidos" => "Demir" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Çetin" "apellidos" => "Saatçi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Asiye" "apellidos" => "Kanbay" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Hakan" "apellidos" => "Büyükoğlan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pulmonary Medicine, Erciyes University School of Medicine, Kayseri, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Genetics, Erciyes University School of Medicine, Kayseri, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Estará o polimorfismo do gene TNF-α relacionado com a função pulmonar e o prognóstico determinados pelo VEMS, IMC, exacerbações e hospitalizações em doentes com DPOC associados ao tabagismo numa população turca?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cigarette smoking is the most common and important cause of chronic obstructive pulmonary disease (COPD). However, COPD develops in only 10–15% of smokers.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In addition, a familial predisposition for COPD and lung function is well known.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> These findings suggest that genetic factors are responsible for COPD. Alpha-1 antitrypsin deficiency is the best-known genetic risk factor for COPD, but such cases are estimated to account for only 1–2%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Tumor necrosis factor (TNF)-α is a cytokine primarily derived from macrophages. Increased concentrations of TNF-α have been found in induced sputum, bronchoalveolar lavage fluid, and bronchial biopsies from patients with COPD compared with healthy smokers.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> These findings have led researchers to further work on TNF-α. A genomic polymorphism resulting in the substitution of the nucleotide adenine (A) for guanine (G) at position-308 within a regulatory region of the TNF-α locus was discovered in 1992.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This polymorphism at position-308 of the TNF-α gene showed elevated TNF-α secretion and blood levels in some studies.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It is necessary to clarify the effects of genetic polymorphisms of the TNF-α gene promoter region for the development of COPD and disease progression. Some conflicting results have been published about the relationship between TNF-α-308 gene polymorphism and COPD. A meta-analysis of twenty four studies showed that TNF-α-308 gene polymorphism is associated with an increased risk of COPD in the Asian population, but this relationship is not significant in the Caucasian population.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Although previous reports showed that the FEV1 and BMI values were lower in COPD patients than in smoker controls, there was no significant difference among G/G, G/A and A/A gene polymorphisms in COPD patients.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–14</span></a> In a report that evaluates the prognosis of COPD and TNF-α gene polymorphism, COPD exacerbation was found to be the most common cause of death.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The aims of the present study were to determine whether TNF-α-308 gene polymorphism was associated with smoking-related COPD and whether it was associated with pulmonary function parameters (PFTs), body mass index (BMI), and prognosis in a Caucasian population.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Subjects</span><p id="par0020" class="elsevierStylePara elsevierViewall">The study was approved by the Research Ethics Committee of Erciyes University School of Medicine in Kayseri, Turkey and all subjects gave written informed consent. Ninety subjects were enrolled from August 2010 to December 2011. The patient group was recruited from the Pulmonary Outpatient Department. It consisted of 60 male adults with COPD. The diagnosis of COPD was made according to the Global Initiative for Chronic Obstructive Lung Disease standards.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The criteria of enrollment were as follows: (1) >40 years old, (2) a smoking history of 20–80 pack-years, (3) available spirometry data for the previous year, (4) post-bronchodilator FEV<span class="elsevierStyleInf">1</span>/FVC <span class="elsevierStyleItalic"><</span>70%, and (5) patient's consent. Patients were excluded if they had had an exacerbation of COPD within the previous 6 weeks and significant reversibility (FEV1 or FVC<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>12% baseline and/or 200<span class="elsevierStyleHsp" style=""></span>ml) to 2.5<span class="elsevierStyleHsp" style=""></span>mg nebulized salbutamol.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The previous year's PFTs and BMI (calculated as weight in kg divided by the square of height in meters) were recorded from files. The annual number of hospitalizations and COPD exacerbations were examined during the last year. Exacerbation of COPD was defined as “an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum that is beyond normal day-to-day variations, is acute in onset and may warrant a change in regular medication”.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> New PFTs were performed by experienced technicians and BMI was calculated.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The control group consisted of 30 male chronic heavy smokers with normal lung function who were recruited randomly from the smoking cessation clinic. The inclusion criteria were as follows: (1) male older than 40 years of age, (2) heavy smoker with a smoking history of 20–80 pack-years, (3) post-bronchodilator FEV<span class="elsevierStyleInf">1</span>/FVC ratio<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>70%, FEV<span class="elsevierStyleInf">1</span>% predicted<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>80%, and FVC % predicted<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>80%, (4) no other pulmonary disease.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Spirometer</span><p id="par0035" class="elsevierStylePara elsevierViewall">All PFTs were performed by experienced lung function technicians with the same standard spirometer (Vmax20 system; SensorMedics, Yorba Linda, CA, USA) according to American Thoracic Society (ATS) recommendations.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The best FVC measurement was recorded along with FEV1 and the FEV1/FVC calculations.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Genotyping protocol</span><p id="par0040" class="elsevierStylePara elsevierViewall">Three milliliters of whole peripheral blood was obtained from each study participant by phlebotomy into a tube containing ethylene diamine tetra-acetic acid (EDTA). DNA was extracted promptly using a MagNA Pure LC DNA Isolation Kit I (Cat. No. 03003990001, Ver. 17.0) supplied by Roche (Mannheim, Germany).</p><p id="par0045" class="elsevierStylePara elsevierViewall">TNF alpha-308 promoter gene polymorphism (rs1800629) was genotyped using the LightCycler real-time PCR system. The primers and hybridization probe for genotyping the -308 promoter polymorphism were designed by and obtained from Tib MolBiol GmbH, Berlin, Germany. The PCR reaction was carried out using the LightCycler real-time PCR machine 480 II (Roche Diagnostics GmbH, Mannheim, Germany), with software version 1.5.0. A reaction volume of 20<span class="elsevierStyleHsp" style=""></span>μl (with 2<span class="elsevierStyleHsp" style=""></span>μl of DNA Master Mix, 1<span class="elsevierStyleHsp" style=""></span>μl of primers probe, 1.6<span class="elsevierStyleHsp" style=""></span>μl of 25<span class="elsevierStyleHsp" style=""></span>mM MgCl<span class="elsevierStyleInf">2</span>, 10.4<span class="elsevierStyleHsp" style=""></span>μl H<span class="elsevierStyleInf">2</span>O and 5<span class="elsevierStyleHsp" style=""></span>μl genomic DNA (10<span class="elsevierStyleHsp" style=""></span>ng)) was amplified in 96-well plates using the FastStart LC 480 II genotyping master kit (Roche Diagnostics GmbH). The PCR protocol for -308 promoter polymorphism consisted of initial denaturation at 95<span class="elsevierStyleHsp" style=""></span>°C for 10<span class="elsevierStyleHsp" style=""></span>min, followed by 45 cycles of denaturation (95<span class="elsevierStyleHsp" style=""></span>°C for 10<span class="elsevierStyleHsp" style=""></span>s, 4.4<span class="elsevierStyleHsp" style=""></span>°C/s), annealing (60<span class="elsevierStyleHsp" style=""></span>°C for 10<span class="elsevierStyleHsp" style=""></span>s, 2.2<span class="elsevierStyleHsp" style=""></span>°C/s) and elongation (72<span class="elsevierStyleHsp" style=""></span>°C for 10<span class="elsevierStyleHsp" style=""></span>s, 4.4<span class="elsevierStyleHsp" style=""></span>°C/s). This was followed by melting curve analysis consisting of 1 cycle at 95<span class="elsevierStyleHsp" style=""></span>°C for 30<span class="elsevierStyleHsp" style=""></span>s (4.4<span class="elsevierStyleHsp" style=""></span>°C/s), 40<span class="elsevierStyleHsp" style=""></span>°C for 2<span class="elsevierStyleHsp" style=""></span>min (1.5<span class="elsevierStyleHsp" style=""></span>°C/s) and a temperature rise to 75<span class="elsevierStyleHsp" style=""></span>°C at a slope of 0.19<span class="elsevierStyleHsp" style=""></span>°C/s with continuous measurement of fluorescence.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">SPSS software (Statistical Package for the Social Sciences, version 15.0, SSPS Inc, Chicago, IL, USA) was used for statistical analyses. The distribution of continuous variables for normality was tested with the One-Sample Kolmogorov–Smirnov test and data are presented as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation (S.D.) or median and interquartile ranges, as appropriate. Demographic characteristics and parameters were compared using the Student <span class="elsevierStyleItalic">t</span>-test or Mann–Whitney <span class="elsevierStyleItalic">U</span> test for the continuous variables, where appropriate. Categorical variables were analyzed by the <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span>-test. According to groups, the before and after values of the quantitative variables were assessed by the mean paired-sample <span class="elsevierStyleItalic">t</span>-test. The power of the study based on the gene polymorphism was 0.068 for (with alpha error of 0.05). Differences were considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Comparison of COPD group and control group</span><p id="par0055" class="elsevierStylePara elsevierViewall">The characteristics of the COPD (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>60) and the control groups (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>30) are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The COPD patients were older (60<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10 vs. 54<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7 years, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) than the control group but had a similar pack-year history (45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17 vs. 41<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19 pack-years, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). PFTs (FEV<span class="elsevierStyleInf">1</span>%, FEV<span class="elsevierStyleInf">1</span>/FVC, FEF 25–75%) in the control group were near normal and significantly greater than those of the COPD group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Mean BMI was also significantly lower in the COPD group (26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 vs. 29<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The genotype frequencies of TNF-α-308 gene polymorphisms in the COPD group were compared with those in control subjects. Forty-four (73%) patients had G/G and 16 (27%) patients had G/A gene polymorphisms in the COPD population; 24 (80%) patients had G/G and 6 (20%) patients had G/A gene polymorphisms in the control group. AA genotypes were not determined in any patient in the two groups. There was no significant difference in the frequency of G/G and G/A genotypes in the COPD population compared with control subjects (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Comparison of COPD patients grouped by genotype</span><p id="par0065" class="elsevierStylePara elsevierViewall">In COPD patients, the mean age and smoking status of patients were compared as groups of TNF-α-308 G/A gene polymorphism (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16) and G/G gene polymorphism (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>44). The mean age [61<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11 (G/A)/60<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10 years (G/G)], the amount of smoking [45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17 (G/A)/45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17 pack-years (G/G)] and active smoking [0 (G/A)/5 (G/G)] was not statistically significant in these groups (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). Also, a comparison of PFTs and BMI before and after one year were not statistically significant (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the comparison of PFTs and BMI in both groups.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Exacerbation and hospitalization data of COPD patients</span><p id="par0070" class="elsevierStylePara elsevierViewall">The exacerbation and hospitalization data of COPD patients are summarized in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. Eleven (69%) patients who had G/A gene polymorphism and 27 (61%) patients who had G/G gene polymorphism in the COPD group had acute COPD exacerbation in the past year. Six (38%) patients with G/A gene polymorphism and 14 (32%) patients with G/G gene polymorphism were hospitalized because of COPD exacerbation. Neither of these differences were statistically significant (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The present study demonstrates that there is no difference in the frequency of G/A and G/G gene polymorphism in patients with COPD compared to healthy, smoking control subjects in a Caucasian population. Many studies have shown an association between COPD and TNF-α-308 gene polymorphism in an Asian population.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17–20</span></a> However, in a Caucasian population, although studies have been conducted in different countries, most of them did not show any association; this was similar to our results.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,21–30</span></a> A large family study from a Boston early-onset COPD study and another American study are the only two studies to show an association between COPD and TNF-α-308 polymorphism in a Caucasian population.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,31</span></a> In addition, a study from our country recently showed a significant difference among COPD stages in terms of TNF-α 308 G/A polymorphism.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> However, a meta-analysis of data for 6118 subjects also showed that TNF-308 gene polymorphisms were significantly associated with an increased risk of COPD among an Asian population but not among a Caucasian population.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In this situation, it seems that polymorphisms in the TNF-α-308 gene that stimulate the production of cytokines are not major genetic determinants for the development of COPD in most of the Caucasian population.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The major etiologic factor for the development of COPD is cigarette smoking. The risk of COPD development among people with a similar history of smoking may be different due to genetic predisposition and/or lifestyles. In a study investigating the association between antioxidant genes and COPD, the definition of “resistant smoker” was used for smokers who did not develop COPD.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Therefore, we identified individuals with a smoking history of 20–80 pack-years and created similar patient and control groups. TNF-α-308 gene polymorphism was found to be ineffective in the development of COPD in these groups which had a similar smoking history.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The second major finding in the present study is that COPD patients with G/A and G/G gene polymorphism had similar PFTs (FEV<span class="elsevierStyleInf">1</span>, FEV<span class="elsevierStyleInf">1</span>%, FEV<span class="elsevierStyleInf">1</span>/FVC) before and after one year evaluation. The FEV<span class="elsevierStyleInf">1</span> value was the most commonly used parameter for monitoring disease progression.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Only one report exists that evaluates the prognosis of TNF-α-308 gene polymorphism in COPD patients.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Keatings et al. showed that AA homozygous patients had less reversible airflow obstruction and a significantly greater mortality (both all-cause and respiratory deaths) on follow-up despite a shorter cigarette smoking history. In another study, the homogenous A genotype in COPD patients was accompanied by a significant reduction in the mean values of the post-bronchodilator FEV<span class="elsevierStyleInf">1</span>, FEV<span class="elsevierStyleInf">1</span>/FVC and FEF25/75% of predicted compared to heterozygous G/A genotypes in COPD.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> However, in the present study, there were no patients with A/A polymorphism for comparison purposes.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Another parameter that was shown to have prognostic importance in patients with COPD was BMI.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> In a study by Wilson et al., BMI was shown to be an important prognostic factor after FEV<span class="elsevierStyleInf">1</span> in male patients with COPD.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Furthermore, low BMI was shown to be independently associated with reduced survival in patients with severe COPD.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In the present study, BMI was significantly lower in patients with COPD than in the healthy smoker control group. When we examined the effect of the TNF-α-308 gene on BMI, neither the current BMI nor the BMI of the previous year were statistically significant between the patients with G/A and G/G gene polymorphisms.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The most important limitation of this study was the low number of patients. In addition, mortality was not examined in the present study. No patients had A/A gene polymorphism, so we have no data about A/A gene polymorphism in our population.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusion</span><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion, there was no difference between smoking-related COPD and control group according to TNF α-308 gene polymorphism in a Caucasian population. In addition, it was shown that important determinants of prognosis of COPD such as FEV<span class="elsevierStyleInf">1</span>, BMI, COPD exacerbation and hospitalization were not associated with TNF-α-308 gene polymorphism.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical disclosures</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Protection of human and animal subjects</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Confidentiality of data</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres549681" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec567276" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres549682" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec567277" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Spirometer" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Genotyping protocol" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Comparison of COPD group and control group" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Comparison of COPD patients grouped by genotype" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Exacerbation and hospitalization data of COPD patients" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusion" ] 9 => array:3 [ "identificador" => "sec0065" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of interest" ] 11 => array:2 [ "identificador" => "xack185528" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-11-29" "fechaAceptado" => "2014-03-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec567276" "palabras" => array:4 [ 0 => "Chronic obstructive pulmonary disease" 1 => "Genetics" 2 => "Polymorphism" 3 => "Tumor necrosis factor-α" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec567277" "palabras" => array:4 [ 0 => "Doença pulmonar obstrutiva crónica" 1 => "Genética" 2 => "Polimorfismo" 3 => "Factor de necrose tumoral alfa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Some conflicting results have been published about the relationship between TNF-α-308 gene polymorphism and chronic obstructive pulmonary disease (COPD). The aim of this study was to determine whether TNF-α-308 gene polymorphism was associated with smoking-related COPD and whether it was associated with pulmonary function parameters (PFTs), body mass index (BMI), and prognosis.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We studied the frequencies of TNF-α-308 gene polymorphism in 90 male subjects (60 subjects with COPD and 30 healthy smokers) in a Caucasian population.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">There was no significant difference in the frequency of G/G and G/A gene polymorphisms in the COPD group compared with control subjects (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). We compared COPD patients as G/A gene polymorphism and G/G gene polymorphism; the PFTs and BMI before and after one year were not statistically significant (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). Also, the exacerbation and hospitalization data of COPD patients were not significant between these groups.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In conclusion, there was no difference between smoking-related COPD and the control group according to TNF α-308 gene polymorphism in a Caucasian population. In addition, it was shown that important determinants of prognosis of COPD such as FEV<span class="elsevierStyleInf">1</span>, BMI, COPD exacerbation and hospitalization were not associated with TNF-α-308 gene polymorphism.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdução</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Foram publicados alguns resultados contraditórios sobre a relação entre o polimorfismo do gene TNF-α -308 e a doença pulmonar obstrutiva crónica (DPOC). O objectivo deste estudo foi determinar se o polimorfismo do gene TNF-α -308 estava associado à DPOC ligada ao tabagismo e se foi associado aos parâmetros de função pulmonar (PFTs), índice de massa corporal (IMC), e prognóstico.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudámos as frequências do polimorfismo do gene TNF-α -308 em 90 indivíduos do sexo masculino (60 indivíduos com DPOC e 30 fumadores saudáveis) numa população caucasiana.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Não houve uma diferença significativa na frequência de polimorfismos genéticos G/G e G/A no grupo de DPOC, em comparação com o grupo de controlo (p>0,05). Comparámos os doentes com DPOC como polimorfismo genético G/A e polimorfismo genético G/G; os PFTs (parâmetros de função pulmonar) e o IMC (índice de massa corporal) antes e depois de um ano não eram estatisticamente significativos (p>0,05). Da mesma forma, os dados de agravamento e hospitalização dos doentes com DPOC não eram significativos entre estes grupos.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusão</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Em conclusão, não existiu uma diferença entre o grupo com DPOC ligada ao tabagismo e o grupo de controlo, de acordo com o polimorfismo do gene TNF α -308, numa população caucasiana. Além disso, foi mostrado que determinantes importantes do prognóstico da DPOC, tal como VEMS, IMC, exacerbações da DPOC e hospitalização não estavam associados ao polimorfismo do gene TNF-α -308.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values are expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD or as absolute numbers. COPD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Chronic obstructive pulmonary disease, FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s, FVC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Forced vital capacity, FEF25–75%<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Forced expiratory flow 25–75%, BMI<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Body mass index.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">COPD (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>60) \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">Controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>30) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Smoking (pack-years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.316 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Current smoking, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (77%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span>/FVC (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEF 25–75 (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BMI (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab887998.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Demographic characteristics and pulmonary test parameters of the COPD patients and healthy control groups.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNF-α-308 Genotype \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">COPD(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>60) (%) \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">Controls(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>30) (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">G/G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 (73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">G/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">A/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab887999.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Genotype frequencies in patient and control groups.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">G/A (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16)</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">G/G (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>44)</th><th class="td" title="table-head " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>1<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>2<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">**</span></a> \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"> \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">Before \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">After \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Before \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">After \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> (L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.947 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.59<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.64<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.309 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.376 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.298 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.866 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>20.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.154 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.345 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.185 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span>/FVC (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.835 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.364 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.661 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.605 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BMI (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.721 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.428 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.375 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.548 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab888000.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Comparison of before values of G/A and G/G group.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Comparison of after values of G/A and G/G group.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Comparison of PFTs and BMI before and after one year grouped by gene polymorphism in patients with COPD.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">G/A (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16) \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">G/G (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>44) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Exacerbation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (69%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hospitalization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (38%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (32%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab888001.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The exacerbation and hospitalization of COPD patients by grouped as gene polymorphism.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic obstructive pulmonary disease surveillance-United States, 1971–2000" "autores" => 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Year/Month | Html | Total | |
---|---|---|---|
2024 November | 8 | 5 | 13 |
2024 October | 49 | 44 | 93 |
2024 September | 42 | 26 | 68 |
2024 August | 59 | 37 | 96 |
2024 July | 40 | 27 | 67 |
2024 June | 34 | 22 | 56 |
2024 May | 42 | 32 | 74 |
2024 April | 49 | 31 | 80 |
2024 March | 38 | 26 | 64 |
2024 February | 47 | 23 | 70 |
2024 January | 37 | 24 | 61 |
2023 December | 28 | 22 | 50 |
2023 November | 30 | 33 | 63 |
2023 October | 28 | 33 | 61 |
2023 September | 24 | 35 | 59 |
2023 August | 28 | 19 | 47 |
2023 July | 21 | 26 | 47 |
2023 June | 23 | 14 | 37 |
2023 May | 53 | 29 | 82 |
2023 April | 46 | 18 | 64 |
2023 March | 93 | 20 | 113 |
2023 February | 66 | 27 | 93 |
2023 January | 26 | 15 | 41 |
2022 December | 45 | 24 | 69 |
2022 November | 87 | 39 | 126 |
2022 October | 45 | 29 | 74 |
2022 September | 22 | 21 | 43 |
2022 August | 33 | 30 | 63 |
2022 July | 32 | 39 | 71 |
2022 June | 17 | 31 | 48 |
2022 May | 47 | 39 | 86 |
2022 April | 25 | 35 | 60 |
2022 March | 34 | 33 | 67 |
2022 February | 31 | 26 | 57 |
2022 January | 24 | 37 | 61 |
2021 December | 20 | 39 | 59 |
2021 November | 30 | 31 | 61 |
2021 October | 34 | 40 | 74 |
2021 September | 17 | 35 | 52 |
2021 August | 37 | 27 | 64 |
2021 July | 25 | 27 | 52 |
2021 June | 20 | 22 | 42 |
2021 May | 29 | 26 | 55 |
2021 April | 69 | 84 | 153 |
2021 March | 66 | 14 | 80 |
2021 February | 69 | 16 | 85 |
2021 January | 32 | 16 | 48 |
2020 December | 36 | 4 | 40 |
2020 November | 59 | 16 | 75 |
2020 October | 37 | 14 | 51 |
2020 September | 85 | 16 | 101 |
2020 August | 58 | 23 | 81 |
2020 July | 93 | 22 | 115 |
2020 June | 108 | 18 | 126 |
2020 May | 92 | 15 | 107 |
2020 April | 90 | 5 | 95 |
2020 March | 70 | 16 | 86 |
2020 February | 69 | 17 | 86 |
2020 January | 96 | 16 | 112 |
2019 December | 64 | 21 | 85 |
2019 November | 90 | 17 | 107 |
2019 October | 93 | 20 | 113 |
2019 September | 69 | 16 | 85 |
2019 August | 238 | 15 | 253 |
2019 July | 270 | 19 | 289 |
2019 June | 271 | 26 | 297 |
2019 May | 296 | 10 | 306 |
2019 April | 244 | 21 | 265 |
2019 March | 274 | 14 | 288 |
2019 February | 278 | 7 | 285 |
2019 January | 266 | 25 | 291 |
2018 December | 220 | 4 | 224 |
2018 November | 56 | 4 | 60 |
2018 October | 64 | 10 | 74 |
2018 September | 31 | 5 | 36 |
2018 August | 32 | 24 | 56 |
2018 July | 71 | 20 | 91 |
2018 June | 65 | 14 | 79 |
2018 May | 114 | 19 | 133 |
2018 April | 74 | 25 | 99 |
2018 March | 59 | 20 | 79 |
2018 February | 40 | 14 | 54 |
2018 January | 36 | 19 | 55 |
2017 December | 50 | 21 | 71 |
2017 November | 33 | 12 | 45 |
2017 October | 26 | 18 | 44 |
2017 September | 25 | 15 | 40 |
2017 August | 23 | 11 | 34 |
2017 July | 16 | 16 | 32 |
2017 June | 27 | 22 | 49 |
2017 May | 29 | 26 | 55 |
2017 April | 15 | 32 | 47 |
2017 March | 10 | 10 | 20 |
2017 February | 5 | 1 | 6 |
2017 January | 9 | 6 | 15 |
2016 December | 9 | 6 | 15 |
2016 November | 7 | 4 | 11 |
2016 October | 5 | 3 | 8 |
2016 September | 6 | 1 | 7 |
2016 August | 6 | 4 | 10 |
2016 July | 6 | 8 | 14 |
2016 June | 0 | 3 | 3 |
2016 May | 0 | 11 | 11 |
2016 April | 22 | 1 | 23 |
2016 March | 39 | 21 | 60 |
2016 February | 39 | 24 | 63 |
2016 January | 26 | 21 | 47 |
2015 December | 27 | 16 | 43 |
2015 November | 11 | 9 | 20 |
2015 October | 22 | 15 | 37 |
2015 September | 32 | 11 | 43 |
2015 August | 31 | 16 | 47 |
2015 July | 36 | 9 | 45 |
2015 June | 22 | 7 | 29 |
2015 May | 36 | 7 | 43 |
2015 April | 45 | 16 | 61 |
2015 March | 36 | 15 | 51 |
2015 February | 95 | 28 | 123 |
2015 January | 150 | 59 | 209 |
2014 December | 91 | 66 | 157 |