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Association Between Chronic Respiratory Diseases and Helicobacter pylori: A Meta-Analysis
Asociación entre enfermedades respiratorias crónicas y Helicobacter pylori: un metaanálisis
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=> "Guo" "email" => array:1 [ 0 => "guo090909@126.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Shandong Cancer Hospital, Jinan, Shandong, China" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asociación entre enfermedades respiratorias crónicas y <span class="elsevierStyleItalic">Helicobacter pylori:</span> un metaanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1051 "Ancho" => 3333 "Tamanyo" => 266929 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis with a random effects model for the combination of <span class="elsevierStyleItalic">H. pylori</span> with chronic obstructive pulmonary disease (COPD).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The prevalence of chronic respiratory diseases (CRDs), including chronic bronchitis and chronic obstructive pulmonary disease (COPD), has increased significantly over the past decades.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a> The etiology of CRDs is well known to be complex. Certain risk factors, such as age, tobacco use and atmospheric pollution, are closely related with CRDs.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Helicobacter pylori</span>, a spiral-shaped, gram-negative bacterium, has been implicated in the risk of gastroduodenal ulcer and gastric cancer.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">4</span></a> In previous studies, increased prevalence of <span class="elsevierStyleItalic">H. pylori</span> seropositivity has been observed in association with several diseases, such as certain heart diseases<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">5</span></a> and allergies.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">To date, several studies, including systematic reviews and meta-analyses, have been performed to evaluate the association between <span class="elsevierStyleItalic">H. pylori</span> and respiratory diseases such as asthma,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a> pulmonary tuberculosis<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">8</span></a> and lung cancer.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">9</span></a> However, no quantitative systematic review has studied the relationship between chronic bronchitis or COPD and <span class="elsevierStyleItalic">H. pylori</span> infection. Although the association between <span class="elsevierStyleItalic">H. pylori</span> infection and CRD has been investigated in different studies,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">10</span></a> results were inconsistent, with some studies indicating no evidence for a relationship between <span class="elsevierStyleItalic">H. pylori</span> and CRD,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> and other suggesting a close relationship.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In order to clarify the association between CRD and <span class="elsevierStyleItalic">H. pylori</span>, we reviewed the literature and produced the first meta-analysis in this area. The possible association may broaden our understanding of the pathological mechanism of CRDs and contribute to their prevention.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Literature Search Strategy</span><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic search was made of the literature, with no limitations for language, in PubMed, Embase, Ovid, Google Scholar and China National Knowledge Infrastructure (CNKI) from inception to October 31, 2013. Search terms used were “chronic respiratory disease”, “chronic bronchitis”, “chronic obstructive pulmonary disease” or “COPD”, combined with “Helicobacter pylori” or “Campylobacter pylori”. When the search retrieved an article in a language other than English, the abstracts were examined for possible inclusion, and the complete texts were then read for any possibly relevant information. Publications that could be of interest were evaluated by examination of the titles and abstracts. The full texts of clearly relevant articles were then obtained for a more detailed examination. Other relevant articles that could have been missed in the initial search were also screened.</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion and Exclusion Criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Criteria for the selection of articles were: (a) the association of <span class="elsevierStyleItalic">H. pylori</span> infection with CRDs had to be clearly described in the studies; (b) the diagnosis of <span class="elsevierStyleItalic">H. pylori</span> infection and the number of cases and controls had to be specified; (c) the sample size, odds ratio (OR) and 95% confidence intervals (CI) or else the data needed for inferring these parameters had to be given; (d) data sourcing and analysis methodology had to be acceptable from a statistical point of view, and (e) studies had to be case-controlled.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The following exclusion criteria were also applied: (a) duplicated publications and reviews; (b) studies with a design and definition manifestly different from the inclusion criteria; (c) non-case–control studies, and (d) lack of information regarding the number of cases and controls and other essential data. After an intensive search, all articles were reviewed according to the above criteria, and a more detailed analysis was made.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data Extraction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data from all eligible publications were carefully extracted by 2 of the authors, working independently, applying the above-mentioned inclusion criteria. In case of discrepancy, consensus was reached by discussion. If no agreement could be reached, the other author was consulted to settle the controversy, and a final decision was reached by majority vote. Collected data were entered in a database.</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Evaluation of Methodological Quality</span><p id="par0045" class="elsevierStylePara elsevierViewall">The methodological quality of all case–control studies was evaluated using the Newcastle–Ottawa Scale (NOS).<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">13</span></a> The NOS is based on the semiquantitative principle, and rates quality according to a star system by which studies are awarded 0–9 stars.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical Analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Odds ratios (ORs) were estimated for CRDs associated with <span class="elsevierStyleItalic">H. pylori</span> for each study. To detect any possible bias in sample size, the ORs and 95% confidence intervals (CI) of each study were plotted against the corresponding number of participants.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Statistical heterogeneity was analyzed using the <span class="elsevierStyleItalic">Q</span> statistic and a value of <span class="elsevierStyleItalic">P</span><.05 was considered statistically significant. If the result of the heterogeneity test was <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>>50%, the random effects model (DerSimonian and Laird)<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">14</span></a> was used for the meta-analysis. Otherwise, the ORs were combined according to the fixed effects model (Mantel and Haenszel).<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">15</span></a> The <span class="elsevierStyleItalic">Z</span>-test was used to determine the significance of the combined OR. Publication bias was evaluated by the fail-safe number (Nfs0.05) for <span class="elsevierStyleItalic">P</span>-values lower than .05 (<span class="elsevierStyleItalic">P</span><.05).<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a> Statistical analysis was performed using Review Manager 5.2 software.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Literature Search and Meta-Analysis Database</span><p id="par0060" class="elsevierStylePara elsevierViewall">Using our search strategy, 369 possibly relevant articles were identified, of which 347 titles were discarded for various reasons after perusal of the titles and abstracts (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The full texts of 22 articles were then obtained for more careful examination. After strict application of the inclusion and exclusion criteria, 9 case–control studies<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">11,12,17–23</span></a> were finally selected for inclusion in the meta-analysis. All these articles were in English.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Information extracted from each article was used to create a database that included the following data points: first author, years of publication, number of cases and controls in each study, and number of subjects with positive <span class="elsevierStyleItalic">H. pylori</span> among the cases and the controls. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the quality scores of the studies included. Mean quality was 7.5 stars. All cases had a diagnosis of chronic bronchitis or COPD, according to the following, strictly implemented, diagnostic criteria. Chronic bronchitis was clinically defined as chronic productive cough for 3 months, in at least 2 consecutive years, in a patient in whom other causes of chronic cough were ruled out. If incomplete reversal of airway obstruction was confirmed by spirometry (postbronchodilator forced expired volume in 1<span class="elsevierStyleHsp" style=""></span>s [FEV<span class="elsevierStyleInf">1</span>] <80% predicted, along with FEV<span class="elsevierStyleInf">1</span>/FVC <70%), a diagnosis of COPD was given. Of the studies included, 8 used radioimmunoassay (ELISA) for IgG serological detection of <span class="elsevierStyleItalic">H. pylori</span><a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">11,12,17,18,20–23</span></a> and only 1 used the <span class="elsevierStyleSup">13</span>C-urea breath test.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">19</span></a> Other necessary data were included in the meta-analysis forest plot (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Heterogeneity Testing</span><p id="par0070" class="elsevierStylePara elsevierViewall">All data were analyzed for heterogeneity. The <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> index was 43%, therefore, a fixed effects model was used to calculate overall OR. Heterogeneity was also analyzed after dividing the data into subgroups. <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> index for the chronic bronchitis subgroup, however, was 0%, so the association between chronic bronchitis and <span class="elsevierStyleItalic">H. pylori</span> was analyzed using the fixed effects model. In contrast, the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> index in the COPD subgroup was 54%, so the random effects model was used.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Quantitative Synthesis</span><p id="par0075" class="elsevierStylePara elsevierViewall">To evaluate the possible relation between <span class="elsevierStyleItalic">H. pylori</span> infection and CRD, data were obtained from 9 case–control studies for inclusion in the meta-analysis. A total of 782 cases and 815 controls were included, of which 547 cases and 427 controls were <span class="elsevierStyleItalic">H. pylori</span>-positive, while 235 cases and 388 controls were <span class="elsevierStyleItalic">H. pylori</span>-negative. As shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>, the overall OR was 2.30 (95% CI: 1.85–2.85) and the <span class="elsevierStyleItalic">Z</span>-value for the overall effect test was 7.52 (<span class="elsevierStyleItalic">P</span><.05).</p><p id="par0080" class="elsevierStylePara elsevierViewall">In view of possible differences between the influence of chronic bronchitis and of COPD on the results, a subgroup analysis was also performed to evaluate the relationship. Four case–control studies with 318 cases and 332 controls<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">18,20,21,23</span></a> were included in the chronic bronchitis subgroup, and the other 5 studies, with 464 cases and 483 controls,<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">11,12,17,19,22</span></a> were included in the COPD subgroup. The OR for the chronic bronchitis subgroup was 2.90 (95% CI: 2.04–4.13) and the <span class="elsevierStyleItalic">Z</span>-value for the overall effect test was 5.92 (<span class="elsevierStyleItalic">P</span><.05) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). As shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>, the OR for the COPD subgroup was 2.11 (95% CI: 1.35–3.29), and the <span class="elsevierStyleItalic">Z</span>-value for the overall effect test was 3.30 (<span class="elsevierStyleItalic">P</span><.05).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Sensitivity Analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">To compare the difference and evaluate the sensitivity of the overall analysis, the random effects model was also applied. The combined OR and 95% CI for all the studies pooled was 2.40 (95% CI: 1.77–3.26), and the <span class="elsevierStyleItalic">Z</span>-value for the overall effect test was 5.66 (<span class="elsevierStyleItalic">P</span><.05), similar to the results obtained in the fixed effects model. Likewise, the random effects and fixed effects models were used to evaluate sensitivity and to compare the differences between the subgroup analyses. The results obtained were largely similar.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Bias Assessment</span><p id="par0090" class="elsevierStylePara elsevierViewall">The fail-safe number (Nfs0.05) for the evaluation of meta-analysis reliability is defined as the number of negative results that could overturn significant results. The Nfs0.05 for the overall meta-analysis was 196, suggesting that the results of the overall meta-analysis were almost entirely unaffected by publication bias. Nfs0.05 was also used to evaluate publication bias in the subgroups. The results were between 50 and 44, suggesting very little publication bias in the results of the subgroup analyses.</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">In this quantitative meta-analysis, we examined the possible relationship between <span class="elsevierStyleItalic">H. pylori</span> infection and CRD by analyzing published case–control studies. To the best of our knowledge, this is the first meta-analysis to be published that is evaluating this association.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Our meta-analysis revealed a significant association between <span class="elsevierStyleItalic">H. pylori</span> infection and CRDs. Summary OR was 2.30 (95% CI: 1.85–2.85), and the <span class="elsevierStyleItalic">Z</span>-value for the overall effect test was 7.52 (<span class="elsevierStyleItalic">P</span><.05), indicating that <span class="elsevierStyleItalic">H. pylori</span> infection may be closely related with CRDs. In view of possible differences between the influence of chronic bronchitis and COPD on the results, a subgroup analysis was also performed, yielding similar results.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Although several previous meta-analyses found no significant association between <span class="elsevierStyleItalic">H. pylori</span> and asthma,<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">7,24</span></a> the results of our meta-analysis, evaluating the possible relationship between <span class="elsevierStyleItalic">H. pylori</span> infection and CRD, were positive. This raises the interesting concept that <span class="elsevierStyleItalic">H. pylori</span> is closely associated with chronic bronchitis and COPD. Moreover, our results were similar to those reported in meta-analyses that found a close association between <span class="elsevierStyleItalic">H. pylori</span> infection and pulmonary tuberculosis<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">8</span></a> or lung cancer.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">9</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The pathogenic mechanisms underlying the positive relationship detected between <span class="elsevierStyleItalic">H. pylori</span> infection and CRD have not yet been clarified.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">25</span></a> One theory suggests that the persistent inflammatory airway response induced by mediators released during <span class="elsevierStyleItalic">H. pylori</span> infection leads to the development of CRD.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">10,26</span></a> Another possible pathogenic mechanism is the increased sensitivity of lung cells and bronchial tissue to external stimulants such as smoke and dust induced by <span class="elsevierStyleItalic">H. pylori</span> infection in the lung,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">9</span></a> thus increasing CRD morbidity.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study has several limitations. Firstly, although the results of the case–control studies were quite reliable,<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">24</span></a> they could have been affected by some confounding factors, such as sex, age, socioeconomic level and smoking habit.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">27</span></a> The initial publications provided only incomplete information on these factors, making it impossible to perform the corresponding subgroup analyses. Secondly, given the limited number of studies and the low sample sizes, results must be interpreted cautiously. Thirdly, only articles published in open access until October 2013 were retrieved, so some published or unpublished studies meeting the inclusion criteria may have been omitted. Consequently, some unavoidable bias is to be expected, even though the Nfs0.05 did not find any significant publication bias in our study. Fourthly, studies suggest that <span class="elsevierStyleItalic">H. pylori</span> Cag A+ seropositivity is more closely related with CRDs than anti-<span class="elsevierStyleItalic">H. pylori</span> IgG antibody seropositivity.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">21</span></a> However, the relationship between <span class="elsevierStyleItalic">H. pylori</span> Cag A+ strains and CRD was not evaluated because additional details on Cag A seropositivity were provided in only 3 studies.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">11,12,21</span></a> Fifthly, <span class="elsevierStyleItalic">H. pylori</span> seropositivity rates may vary widely, depending on the different detection methods used. In the series included in our study, the <span class="elsevierStyleSup">13</span>C-urea breath test was used for the detection of <span class="elsevierStyleItalic">H. pylori</span> in only 1 study,<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">19</span></a> while an ELISA<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">11,12,17,18,20–23</span></a> method was used in the others.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion, the results of the overall analysis and subgroup analysis suggest a significant association between <span class="elsevierStyleItalic">H. pylori</span> and CRD. Perhaps the time has come to conduct well-designed studies in large series to clarify the pathogenic mechanisms and to answer questions on the effects of eradication treatment on diseases of the respiratory tract.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0125" class="elsevierStylePara elsevierViewall">This study was funded by Shandong Cancer Hospital.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of Interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors state that they have no financial or personal relationship with other persons or organizations that might inappropriately influence their work and they have no professional or personal interests of any other type, nature or class in any product, service and/or company that could be interpreted as influential in the opinion presented in this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres516629" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec537547" "titulo" => "Keyword" ] 2 => array:3 [ "identificador" => "xres516628" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec537546" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and Methods" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0015" "titulo" => "Literature Search Strategy" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion and Exclusion Criteria" ] ] ] 1 => array:3 [ "identificador" => "sec0025" "titulo" => "Data Extraction" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Evaluation of Methodological Quality" ] ] ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Literature Search and Meta-Analysis Database" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Heterogeneity Testing" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Quantitative Synthesis" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Sensitivity Analysis" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Bias Assessment" ] ] ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-02-10" "fechaAceptado" => "2014-03-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keyword" "identificador" => "xpalclavsec537547" "palabras" => array:5 [ 0 => "<span class="elsevierStyleItalic">Helicobacter pylori</span>" 1 => "Chronic respiratory diseases" 2 => "Chronic obstructive pulmonary disease" 3 => "Chronic bronchitis" 4 => "Meta-analysis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec537546" "palabras" => array:5 [ 0 => "<span class="elsevierStyleItalic">Helicobacter pylori</span>" 1 => "Enfermedades respiratorias crónicas" 2 => "Enfermedad pulmonar obstructiva crónica" 3 => "Bronquitis crónica" 4 => "Metaanálisis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The prevalence of chronic respiratory diseases (CRDs), including chronic bronchitis and chronic obstructive pulmonary disease (COPD), has increased significantly over the past decades. Several studies suggested that <span class="elsevierStyleItalic">Helicobacter pylori</span> infection may be related to the development of CRDs, but the results were not consistent. We carried out a meta-analysis to evaluate the potential association of <span class="elsevierStyleItalic">H. pylori</span> infection with CRDs.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a systematic literature search in PubMed, Embase, Ovid, Google Scholar and CNKI from inception to October 31, 2013. The following search terms were used: “chronic respiratory disease,” “chronic bronchitis,” “chronic obstructive pulmonary disease” or “COPD” in combination with “Helicobacter pylori” or “Campylobacter pylori.” According to established inclusion criteria, we selected all eligible published papers and then extracted essential data. To evaluate the association of <span class="elsevierStyleItalic">H. pylori</span> with chronic bronchitis and COPD, an overall analysis and subgroup analyses were conducted.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 9 case–control studies comprising 782 cases and 815 controls were included in the study. Pooled ORs were 2.30 (95% CI: 1.85–2.85) in the overall analysis, 2.90 (95% CI: 2.04–4.13) in the chronic bronchitis subgroup, and 2.11 (95% CI: 1.35–3.29) in the COPD subgroup.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The results of the overall analysis and subgroup analyzed suggest a significant association between <span class="elsevierStyleItalic">H. pylori</span> and CRDs. Further studies are needed to clarify the pathogenetic mechanisms involved.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de las enfermedades respiratorias crónicas (ERC), incluida la bronquitis crónica y la enfermedad pulmonar obstructiva crónica (EPOC), ha aumentado de manera significativa a lo largo de las últimas décadas. Varios estudios han sugerido que la infección por <span class="elsevierStyleItalic">Helicobacter pylori</span> puede estar relacionada con la aparición de las ERC, pero los resultados presentados no han sido uniformes. Con el objetivo de evaluar la posible asociación de la infección por <span class="elsevierStyleItalic">H. pylori</span> con las ERC, llevamos a cabo el presente metaanálisis.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Realizamos una búsqueda bibliográfica sistemática en PubMed, Embase, Ovid, Google Scholar y CNKI desde su inicio hasta el 31 de octubre de 2013. Los términos de búsqueda utilizados fueron los siguientes: «chronic respiratory disease», «chronic bronchitis», «chronic obstructive pulmonary disease» o «COPD» en combinación con «Helicobacter pylori» o «Campylobacter pylori». Según los criterios de inclusión establecidos, seleccionamos todos los artículos publicados elegibles y extrajimos los datos esenciales. Para evaluar la asociación de <span class="elsevierStyleItalic">H. pylori</span> con la bronquitis crónica y la EPOC se realizó un análisis global y se llevaron a cabo diversos análisis de subgrupos, respectivamente.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Finalmente se incluyeron en los análisis un total de 9 estudios de casos y controles en los que se incluyeron 782 casos y 815 controles. La OR combinada fue de 2,30 (IC 95%: 1,85–2,85) para el análisis global, de 2,90 (IC 95%: 2,04–4,13) para el análisis del subgrupo de bronquitis crónica y de 2,11 (IC 95%: 1,35–3,29) para el análisis del subgrupo de EPOC.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los resultados del análisis global y de los análisis de subgrupos sugieren una asociación significativa entre <span class="elsevierStyleItalic">H. pylori</span> y ERC. Serán necesarios nuevos estudios para esclarecer los mecanismos patogénicos.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Wang L, Guan Y, Li Y, Liu X, Zhang Y, Wang F, et al. Asociación entre enfermedades respiratorias crónicas y <span class="elsevierStyleItalic">Helicobacter pylori:</span> un metaanálisis. Arch Bronconeumol. 2015;51:273-278.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1774 "Ancho" => 1705 "Tamanyo" => 208031 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow chart of studies included or excluded.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1377 "Ancho" => 3333 "Tamanyo" => 361723 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis with a fixed effects model for the association of <span class="elsevierStyleItalic">H. pylori</span> infection and chronic respiratory diseases (CRD).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 967 "Ancho" => 3333 "Tamanyo" => 246849 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis with fixed effect model for the association of <span class="elsevierStyleItalic">H. pylori</span> and chronic bronchitis.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1051 "Ancho" => 3333 "Tamanyo" => 266929 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis with a random effects model for the combination of <span class="elsevierStyleItalic">H. pylori</span> with chronic obstructive pulmonary disease (COPD).</p>" ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">ELISA: enzyme-linked immunosorbent assay; HP: <span class="elsevierStyleItalic">Helicobacter pylori</span>; Ig: immunoglobulin.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author, year \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">Country \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">Type of study \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">Detection method \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">Sample \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">CaseHP(+)/n \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">ControlHP(+)/n \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">Quality score \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">Caselli et al., 1999<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Italy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49/60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40/69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \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">Roussos et al., 2002<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">18</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Greece \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">120/144 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72/120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Jun et al., 2006<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">21</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">China \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40/46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29/48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Kanbay et al., 2005<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">20</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45/68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48/95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \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">Roussos et al., 2005<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">12</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Greece \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98/126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69/126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gencer et al., 2007<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">22</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38/49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25/50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \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">Siva et al., 2013<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">United Kingdom \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35/64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hashemi et al., 2011<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iran \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA (<span class="elsevierStyleItalic">H. pylori</span> IgG) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32/90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30/90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pronail et al., 2004<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hungary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cases and controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleSup">13</span>C-urea breath test \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><td class="td" title="table-entry " align="char" valign="top">90/135 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">110/200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab833838.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Characteristics 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 1 | 2 |
| 2024 October | 63 | 27 | 90 |
| 2024 September | 64 | 18 | 82 |
| 2024 August | 87 | 53 | 140 |
| 2024 July | 65 | 25 | 90 |
| 2024 June | 92 | 23 | 115 |
| 2024 May | 122 | 31 | 153 |
| 2024 April | 70 | 36 | 106 |
| 2024 March | 72 | 20 | 92 |
| 2024 February | 56 | 23 | 79 |
| 2024 January | 1 | 0 | 1 |
| 2023 March | 9 | 5 | 14 |
| 2023 February | 69 | 22 | 91 |
| 2023 January | 53 | 22 | 75 |
| 2022 December | 68 | 28 | 96 |
| 2022 November | 95 | 34 | 129 |
| 2022 October | 50 | 35 | 85 |
| 2022 September | 67 | 38 | 105 |
| 2022 August | 50 | 49 | 99 |
| 2022 July | 51 | 43 | 94 |
| 2022 June | 58 | 38 | 96 |
| 2022 May | 53 | 35 | 88 |
| 2022 April | 41 | 28 | 69 |
| 2022 March | 55 | 41 | 96 |
| 2022 February | 55 | 37 | 92 |
| 2022 January | 49 | 56 | 105 |
| 2021 December | 53 | 41 | 94 |
| 2021 November | 59 | 54 | 113 |
| 2021 October | 45 | 31 | 76 |
| 2021 September | 43 | 47 | 90 |
| 2021 August | 23 | 34 | 57 |
| 2021 July | 59 | 38 | 97 |
| 2021 June | 60 | 48 | 108 |
| 2021 May | 41 | 33 | 74 |
| 2021 April | 118 | 54 | 172 |
| 2021 March | 70 | 33 | 103 |
| 2021 February | 60 | 26 | 86 |
| 2021 January | 48 | 36 | 84 |
| 2020 December | 33 | 27 | 60 |
| 2020 November | 36 | 20 | 56 |
| 2020 October | 78 | 25 | 103 |
| 2020 September | 90 | 15 | 105 |
| 2020 August | 128 | 17 | 145 |
| 2020 July | 116 | 21 | 137 |
| 2020 June | 55 | 12 | 67 |
| 2020 May | 61 | 15 | 76 |
| 2020 April | 41 | 20 | 61 |
| 2020 March | 43 | 9 | 52 |
| 2020 February | 52 | 22 | 74 |
| 2020 January | 64 | 22 | 86 |
| 2019 December | 58 | 21 | 79 |
| 2019 November | 49 | 30 | 79 |
| 2019 October | 38 | 17 | 55 |
| 2019 September | 33 | 13 | 46 |
| 2019 August | 44 | 16 | 60 |
| 2019 July | 49 | 15 | 64 |
| 2019 June | 39 | 52 | 91 |
| 2019 May | 45 | 22 | 67 |
| 2019 April | 56 | 38 | 94 |
| 2019 March | 56 | 20 | 76 |
| 2019 February | 45 | 17 | 62 |
| 2019 January | 43 | 25 | 68 |
| 2018 December | 51 | 17 | 68 |
| 2018 November | 107 | 19 | 126 |
| 2018 October | 90 | 17 | 107 |
| 2018 September | 22 | 13 | 35 |
| 2018 May | 24 | 0 | 24 |
| 2018 April | 30 | 9 | 39 |
| 2018 March | 41 | 10 | 51 |
| 2018 February | 34 | 10 | 44 |
| 2018 January | 21 | 9 | 30 |
| 2017 December | 45 | 10 | 55 |
| 2017 November | 33 | 6 | 39 |
| 2017 October | 27 | 7 | 34 |
| 2017 September | 39 | 15 | 54 |
| 2017 August | 33 | 13 | 46 |
| 2017 July | 25 | 9 | 34 |
| 2017 June | 58 | 40 | 98 |
| 2017 May | 60 | 23 | 83 |
| 2017 April | 31 | 7 | 38 |
| 2017 March | 31 | 22 | 53 |
| 2017 February | 68 | 13 | 81 |
| 2017 January | 11 | 9 | 20 |
| 2016 December | 37 | 10 | 47 |
| 2016 November | 70 | 11 | 81 |
| 2016 October | 61 | 14 | 75 |
| 2016 September | 114 | 26 | 140 |
| 2016 August | 52 | 15 | 67 |
| 2016 July | 36 | 8 | 44 |
| 2016 March | 1 | 0 | 1 |
| 2016 February | 2 | 0 | 2 |
| 2016 January | 1 | 0 | 1 |
| 2015 December | 1 | 0 | 1 |
| 2015 October | 32 | 3 | 35 |
| 2015 September | 24 | 9 | 33 |
| 2015 August | 1 | 1 | 2 |
| 2015 July | 0 | 1 | 1 |
| 2015 June | 0 | 1 | 1 |
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