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namely biomass and occupational dust or chemicals&#46; The term biomass defines the energy obtained from the combustion of organic products&#46; This combustion produces fumes that can be inhaled&#44; causing bronchial inflammation in susceptible individuals&#44; and secondary bronchial obstruction&#44; indistinguishable from COPD in many respects&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> Furthermore&#44; occupational exposure to dust&#44; gases or volatile chemicals can also cause COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">5</span></a> However&#44; it is common to find patients who besides being exposed to these substances also smoke or have smoked&#44; so it is sometimes difficult to determine to what extent each substance has contributed to the development of COPD&#59; moreover&#44; both substances have an additive risk factor for COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It is frequently reported in the literature that biomass is the most frequently inhaled substance after tobacco smoke in developing countries&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> However&#44; the frequency of exposure depends on the geographical area where it is studied&#44; since the use of biomass differs depending on the region studied&#46; In Spain&#44; biomass and occupational dust exposures have not been fully described and only 1 study has provided some information about exposure to substances other than tobacco in a population of patients with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> This study analyzes the information from the On-Sint study&#44; presents data on exposure to substances other than tobacco in this cohort of COPD patients and assesses their impact on the clinical presentation of the disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This study is a cross-sectional analysis of the On-Sint study&#46; The methodology of the On-Sint study has been extensively described elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> Briefly&#44; this is an observational&#44; nationwide&#44; real-life&#44; cohort study&#44; in which patients diagnosed with COPD were recruited between December 2011 and April 2013 by Primary Care &#40;PC&#41; and Secondary Care &#40;SC&#41; physicians&#46; Consecutive patients aged &#62;40 years who were smokers or ex-smokers with a history of &#62;10 pack-years&#44; diagnosed with COPD&#44; with a complete clinical history of respiratory symptoms&#44; able to complete the CAT questionnaire&#44; and who gave their written informed consent were selected to participate in the study&#46; Ethical approval was granted by the Institutional Review Board from Servicio Gallego de Salud &#40;SERGAS&#41; registry number 2011&#47;359&#46; In order to record real-life clinical behavior of participant doctors&#44; the only exclusion criterion considered in the study protocol was participation in any other clinical trial at the time of inclusion&#46; In addition&#44; patients with pulmonary diseases associated with occupational factors including occupational asthma&#44; hypersensitivity pneumonia or interstitial lung diseases were also excluded&#46; In order to make a real-life evaluation&#44; patients were recruited by PC and SC physicians with no matching for gender&#44; age&#44; lung function or any clinical features&#46; Sample size was calculated according to the prevalence and the degree of underdiagnosis of COPD in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a> A planned total of 1440 patients with COPD was expected to constitute a sample of 0&#46;1&#37; of the study population&#44; assuming 10&#37; of patients would have no valid information&#46; Although a uniform distribution of recruitment within the country was planned including all regions in the country&#44; the selection of participant investigators was voluntary&#44; with no attempt to achieve representative sampling&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">During the inclusion visit&#44; patients underwent a clinical evaluation&#44; which included the presence of risk factors for COPD&#44; not only tobacco smoke&#44; but also other inhaled substances&#46; Smoking history was collected&#44; including current smoking status and cumulative consumption in pack-years&#46; Occupational and biomass exposure was self-reported&#46; Patients were asked about their previous exposures&#46; In particular&#44; they were asked if they had been exposed to any other risk factor and&#44; if they replied in the affirmative&#44; the exact exposure was determined&#46; Exposure to other substances was categorized into three groups&#58; occupational dust and chemicals&#44; biomass fuels&#44; or other exposures&#46; The participating centers were classified according to the population of the locality where they were in rural &#40;&#60;<span class="elsevierStyleHsp" style=""></span>5&#44;000 inhabitants&#41;&#44; semiurban &#40;5&#44;000&#8211;19&#44;999 inhabitants&#41; and urban &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>20&#44;000 inhabitants&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The CAT questionnaire was administered to all participants in the inclusion visit&#46; The questionnaire was self-administered or administered by the investigator if any patient had reading&#44; writing or sight difficulties&#46; If more than two questions were unanswered&#44; the questionnaire was considered invalid&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical Computations</span><p id="par0035" class="elsevierStylePara elsevierViewall">Although cases were recruited by respiratory and primary care physicians&#44; all patients were followed up by general practitioners&#44; so comparison between PC and SC was impractical and would have produced confounding results&#46; Consequently&#44; all patients were analyzed together&#46; In addition&#44; since the sample was not intended to be representative of the different regions&#44; we did not compare the impact of different exposures by regions&#46; Statistical computations were performed using the Statistical Package for Social Sciences &#40;SPSS&#44; IBM Corporation Somers&#44; NY&#44; US&#41;&#44; version 20&#46;0&#46; Absolute and relative frequencies for categorical questions were used to describe variables&#44; together with the inter-regional range &#40;IRR&#41;&#44; expressing the range of the means or percentages within the different regions&#44; allowing us to further assess heterogeneity&#46; The IRR is expressed as a percentage for qualitative variables&#44; while quantitative variables are expressed by unit of measure&#46; Geographical maps were constructed using Microsoft PowerMap for Microsoft Excel 2013 &#40;Microsoft Corporation&#44; Redmond&#44; WA&#41;&#46; Bivariate analyses comparing cases with tobacco smoke as the only risk factor with those with additional risk factors were performed with the chi-squared test or the unpaired Student <span class="elsevierStyleItalic">T</span> test&#44; after checking the equality of the variances with the Levene test&#46; Variables with a <span class="elsevierStyleItalic">P</span> value &#60;&#46;1 were entered into a backward stepwise multivariate binomial logistic regression analysis with the presence of additional risk factors as the dependent variable&#46; A <span class="elsevierStyleItalic">P</span> value &#60;&#46;05 was considered significant&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">During the study period&#44; 1264 patients were included in the study&#46; Of these&#44; 50 &#40;4&#46;0&#37;&#41; patients were excluded for not fulfilling the inclusion criteria&#46; Thus&#44; the sample size of the On-Sint cohort was 1214 patients with COPD&#44; of which 857 &#40;70&#46;6&#37;&#41; were recruited by PC and 357 &#40;29&#46;4&#37;&#41; by SC physicians&#46; The frequency of the different risk factors for COPD is depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; All patients were smokers or ex-smokers as per the inclusion criteria&#46; However&#44; 1012 &#40;83&#46;4&#37;&#41; had tobacco as the only risk factor whereas 202 &#40;16&#46;6&#37;&#41; had an additional exposure&#46; The geographical distribution of this exposure is depicted in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; showing greater exposure in the northern parts of the country and on the east coast&#46; Biomass exposure was rather low&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The differences between COPD with tobacco as the only risk factor versus COPD with additional risk factors are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The main factors associated with having an added risk factor were gender&#44; age&#44; chronic sputum production&#44; the Charlson index&#44; CAT score&#44; long-term oxygen therapy&#44; short-acting &#946;<span class="elsevierStyleInf">2</span> agonists&#44; inhaled steroids&#44; and the use of mucolytics&#46; The results of the multivariate analysis including these variables are presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Male gender&#44; CAT score and rurality were associated with having an additional risk factor&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">This is the first study to show the frequency of exposure to other risk factors in addition to tobacco&#44; and the distribution within the different Spanish regions&#44; showing a greater exposure in the northern part of the country and on the east coast&#46; In addition&#44; the study shows the clinical variables associated with this exposure&#44; indicating that COPD caused by tobacco plus an additional risk factor has some similarities with traditional COPD&#44; except that it is more frequent in men&#44; has a greater impact on HRQL for a similar functional impairment&#44; and is associated with rural areas&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Various studies have provided evidence that a considerable proportion of individuals with COPD present non-tobacco risk factors&#46; The <span class="elsevierStyleItalic">Burden of Obstructive Lung Disease</span> &#40;BOLD&#41; Study evaluated data from 14 countries and found that among 4291 never smokers&#44; 6&#46;6&#37; met criteria for mild COPD&#44; and 5&#46;6&#37; met criteria for moderate to very severe disease&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> Occupational exposures leading to COPD have been described for several jobs&#46; High exposure to gases or fumes was associated with chronic bronchitis<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> and the relationship with lung function decline or chronic respiratory symptoms has been described in welders&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> agricultural workers&#44;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">13&#44;14</span></a> and different industries&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">15&#8211;17</span></a> A population-based study in north-east England investigated respiratory symptoms and the prevalence of spirometrically defined COPD between 2002 and 2004&#46; The prevalence of respiratory symptoms was 55&#37; and COPD was present in 10&#37; of subjects&#46; Interestingly&#44; COPD and respiratory symptoms were associated with occupational exposures&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a> In the USA the prevalence of COPD according to occupation has recently been reported for different occupational groups on the basis of the National Health Interview Survey Occupational Codes&#44; with a prevalence of below 5&#37; for all occupational exposures&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The impact of biomass exposure is also well documented as a risk factor for COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> Moreover&#44; an improvement in lung function and prognosis has been shown when air pollution from biomass is reduced&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">20&#44;21</span></a> However&#44; biomass is used much less in a developed country like Spain&#46; In our cohort&#44; the frequency of occupational exposure was higher than reported for biomass exposure&#46; In particular&#44; the northern part of the country is more frequently exposed than the south&#44; probably reflecting the differences in the distribution of industries throughout the country&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Our study has found some associations between additional smoke exposure and clinical characteristics&#46; The association with male gender seems obvious since in Spain the jobs involving occupational exposure are mostly performed by men&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">22</span></a> A previous cross-sectional analysis reported that COPD with exposure to vapor&#44; dust&#44; gas or fumes at any time was associated with older age&#44; male gender&#44; work-related respiratory disability&#44; current wheezing and hay fever&#44; despite similar severity of airflow obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">23</span></a> However&#44; while this is true for our community&#44; in different regions in different countries including rural areas or agricultural settings&#44; a relationship with female gender has been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">18&#44;24</span></a> In addition&#44; we found an association with a more impaired health status as measured by the CAT score&#44; suggesting a higher impact of the disease for a similar lung function&#46; Previous studies have also identified a relationship between occupational exposure and health status&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a> so our data confirm previous associations in a cohort of patients from a country with specific characteristics with regard to non-tobacco COPD risk factor exposure&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Although we were not able to find any other associations&#44; the type of COPD may also be influenced by the type of smoke&#46; Previous studies have found that female patients with wood smoke-related COPD do not appear to develop emphysema as much as individuals with tobacco-related COPD&#44; despite presenting severe airway involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a> In Mexico&#44; it has also been reported that biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure&#44; suggesting an airway-predominant phenotype&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a> Unfortunately&#44; the methodology used in the present study did not allow us to investigate these differences in the different respiratory compartments&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The CAT score is a self-administered health status questionnaire for assessing the impact of COPD on patients&#46; Different studies have demonstrated its good psychometric properties and its association with several clinically relevant outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> Accordingly&#44; CAT is able to capture part of the variability in the clinical impact of the disease which is not evaluated by lung function&#46; In this study&#44; we found that patients with additional exposures expressed a different impact of the disease as measured by CAT&#44; suggesting that COPD with other risk factors may have a more profound impact for the same lung function impairment&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Several issues must be considered for the correct interpretation of our data&#46; Occupational and biomass exposure was self-reported&#46; Various validated questionnaires are available in the literature for evaluating the different exposures in a formal occupational interview&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> However&#44; for the sake of simplicity we opted for self-reported recording of the information&#46; Similarly&#44; we recorded the history of exposure&#44; but not the intensity of this exposure&#46; A recent study has validated a biomass exposure index to quantify the amount of biomass exposure during a life-time&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a> Additionally&#44; we did not record the nature of the biomass or the different jobs&#44; which may have provided extra information&#46; Another aspect that merits consideration is that&#44; in order to make the project affordable&#44; we collected a limited number of variables for analysis&#46; Thus&#44; it is possible that future trials including a higher number of variables may yield a more comprehensive overview&#46; Finally&#44; the sample size was not estimated to allow representative geographical distribution sampling or to allow comparisons between regions&#46; Consequently&#44; the analysis did not attempt to make direct comparisons between the geographical areas within the country&#46; Nonetheless&#44; even with these limitations&#44; we believe that the information presented here represents the best updated information available on different exposures in Spain&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In summary&#44; our study shows the different distribution of exposure to other risk factors in addition to tobacco in the different Spanish regions&#44; showing a greater exposure in the northern part of the country and the east coast&#46; Our study shows the clinical variables associated with this exposure that characterize COPD caused by tobacco plus an additional risk factor&#46; The information provided here could serve as a guide to alert health planners and doctors to the potential effects of these substances and take actions to improve prevention and early diagnosis&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0090" class="elsevierStylePara elsevierViewall">This project was funded by an unrestricted grant from <span class="elsevierStyleGrantSponsor" id="gs1">Novartis Farmac&#233;utica</span>&#44; SA&#44; Spain&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of Interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Although tobacco smoke is the main risk factor for chronic obstructive pulmonary disease &#40;COPD&#41;&#44; other inhaled toxics have also been associated with the disease&#46; The present study analyzes data from exposure to these substances in a cohort of patients with COPD and assesses their impact on the clinical presentation of the disease&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This is a cross-sectional analysis of the <span class="elsevierStyleItalic">Clinical presentation&#44; diagnosis and course of chronic obstructive pulmonary disease</span> &#40;On-Sint&#41; study&#46; All patients were smokers or ex-smokers as per protocol&#46; In addition&#44; during the inclusion visit patients were enquired about their occupational and biomass exposure history&#46; The clinical features of patients with and without an added risk factor to tobacco were compared and those significant were entered in a multivariate logistic regression analysis&#44; expressed as odds ratio &#40;OR&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The sample size was 1214 patients with COPD&#44; of which 1012 &#40;83&#46;4&#37;&#41; had tobacco as the only risk factor and 202 &#40;16&#46;6&#37;&#41; had additional ones&#44; mainly 174 &#40;14&#46;3&#37;&#41; with occupational gases and 32 &#40;2&#46;6&#37;&#41; with biomass exposure&#46; The geographical distribution of this exposure showed a preference for the northern parts of the country and the East coast&#46; The biomass exposure was rather low&#46; Male gender &#40;OR&#58; 2&#46;180&#41;&#44; CAT score &#40;OR&#58; 1&#46;036&#41; and the use of long-term oxygen therapy &#40;OR&#58; 1&#46;642&#41; were associated with having an additional risk factor in the multivariate analysis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Occupational exposures are more common than biomass in Spain&#46; COPD caused by tobacco plus other inhalants has some differential features and a more impaired quality of life&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Aunque el humo del tabaco es el principal factor de riesgo de la enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41;&#44; tambi&#233;n se han relacionado con la enfermedad otros agentes t&#243;xicos inhalados&#46; El presente estudio analiza datos de la exposici&#243;n a estas sustancias y eval&#250;a su impacto sobre la presentaci&#243;n cl&#237;nica de la enfermedad en una cohorte de pacientes con EPOC&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se trata de un an&#225;lisis transversal del estudio <span class="elsevierStyleItalic">Presentaci&#243;n cl&#237;nica&#44; diagn&#243;stico y evoluci&#243;n de la enfermedad pulmonar obstructiva cr&#243;nica</span> &#40;On-Sint&#41;&#46; De conformidad con el protocolo&#44; todos los pacientes eran fumadores o exfumadores&#46; Durante la visita de inclusi&#243;n se interrog&#243; a los pacientes acerca de sus antecedentes de exposici&#243;n laboral a t&#243;xicos y a combusti&#243;n de biomasa&#46; Las caracter&#237;sticas cl&#237;nicas de los pacientes que presentaban alg&#250;n factor de riesgo adem&#225;s del tabaco se compararon con las de los pacientes que no presentaban factores de riesgo adicionales&#44; y los factores que indicaron ser significativos fueron incluidos en un an&#225;lisis de regresi&#243;n log&#237;stica multivariante&#44; expresados en oportunidades relativas &#40;<span class="elsevierStyleItalic">odds ratio</span> &#91;OR&#93;&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La muestra incluy&#243; 1&#46;214 pacientes con EPOC&#44; en 1&#46;012 &#40;83&#44;4&#37;&#41; de los cuales el tabaco era el &#250;nico factor de riesgo&#46; En 202 &#40;16&#44;6&#37;&#41; se constataron otros factores&#44; en 174 &#40;14&#44;3&#37;&#41; principalmente la exposici&#243;n a gases en el &#225;mbito laboral y en 32 &#40;2&#44;6&#37;&#41; la exposici&#243;n a combusti&#243;n de biomasa&#46; La distribuci&#243;n geogr&#225;fica de esta exposici&#243;n fue mayor en la zona norte y la costa este del pa&#237;s&#46; La exposici&#243;n a humo de biomasa fue relativamente baja&#46; El an&#225;lisis multivariante mostr&#243; asociaciones entre la presentaci&#243;n de un factor de riesgo adicional y el sexo masculino &#40;OR&#58; 2&#44;180&#41;&#44; la puntuaci&#243;n CAT &#40;OR&#58; 1&#44;036&#41; y el uso de oxigenoterapia cr&#243;nica &#40;OR&#58; 1&#44;642&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En Espa&#241;a&#44; la exposici&#243;n laboral a t&#243;xicos inhalados es m&#225;s frecuente que la exposici&#243;n a humo de biomasa&#46; La EPOC causada por el tabaco y otros productos inhalados tiene algunas caracter&#237;sticas diferenciales y provoca un mayor deterioro de la calidad de vida&#46;</p></span>"
        "secciones" => array:4 [
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            "titulo" => "Introducci&#243;n"
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            "titulo" => "M&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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    "NotaPie" => array:1 [
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; L&#243;pez-Campos JL&#44; Fern&#225;ndez-Villar A&#44; Calero-Acu&#241;a C&#44; Represas-Represas C&#44; L&#243;pez-Ram&#237;rez C&#44; Leiro Fern&#225;ndez V&#44; et al&#46; Exposici&#243;n laboral y a biomasa en la EPOC&#58; resultados de un an&#225;lisis transversal del estudio On-Sint&#46; Arch Bronconeumol&#46; 2017&#59;53&#58;7&#8211;12&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Geographical distribution for &#40;a&#41; additional non-tobacco risk factors&#44; &#40;b&#41; occupational exposures&#44; and &#40;c&#41; biomass exposure&#44; in a smoking population&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Average data expressed as mean &#40;standard deviation&#41; or absolute &#40;relative&#41; frequencies depending on the nature of the variable&#46; The inter-regional range is expressed as percentage for qualitative variables&#44; while quantitative variables are expressed in its unit of measure&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inter-regional Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Tobacco only</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Occupational dusts and chemicals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">174 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Biomass&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;0&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;10&#46;5&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Prevalence of the Different COPD Risk Factors&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Data expressed as mean &#40;standard deviation&#41; or absolute &#40;relative&#41; frequencies depending on the nature of the variable&#46; MRC&#58; Medical Research Council scale&#46; ICS&#58; inhaled steroids&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \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> Value<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender &#40;males&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">776 &#40;76&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">179 &#40;88&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#46;1 &#40;9&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#46;8 &#40;9&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rural &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63 &#40;6&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;12&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;7 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;8 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Current smokers &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">271 &#40;26&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47 &#40;23&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobacco consumption &#40;pack-years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;1 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;4 &#40;20&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyspnea &#40;MRC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;0&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic sputum production &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">718 &#40;70&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">158 &#40;78&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exacerbations in the previous year &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Two or more exacerbations &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">637 &#40;62&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">128 &#40;63&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Comorbidities &#40;Charlson&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyslipemia &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">497 &#40;49&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">106 &#40;52&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arterial hypertension &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">620 &#40;62&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137 &#40;68&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#46;4 &#40;19&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#46;6 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#46;9 &#40;19&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;0 &#40;22&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">COPD Assessment Test &#40;points&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;9 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#46;2 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Long term oxygen therapy &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">132 &#40;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49 &#40;24&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Short-acting &#946;<span class="elsevierStyleInf">2</span> agonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">352 &#40;34&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">84 &#40;41&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;077&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Short-acting muscarinic antagonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77 &#40;7&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Long-acting &#946;<span class="elsevierStyleInf">2</span> agonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">778 &#40;76&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">152 &#40;75&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Long-acting muscarinic antagonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">643 &#40;63&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">132 &#40;65&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inhaled steroids &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">516 &#40;51&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">119 &#40;58&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;045&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ICS dose &#40;&#956;g&#47;day beclomethasone&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1044&#46;4 &#40;591&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1000&#46;5 &#40;591&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic steroids &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Methylxanthines &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">99 &#40;9&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;12&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mucolytics &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">265 &#40;26&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66 &#40;32&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;069&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;545&#8211;3&#46;786&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;356&#8211;3&#46;505&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;023&#8211;1&#46;063&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;036&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;013&#8211;1&#46;060&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Semi-urban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;440&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;587&#8211;3&#44;752&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;232&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;413&#8211;3&#44;524&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rural&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;889&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;739&#8211;4&#44;799&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;813&#8211;5&#44;349&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
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        0 => array:2 [
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            0 => array:3 [
              "identificador" => "bib0150"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global strategy for the diagnosis&#44; management&#44; and prevention of chronic obstructive pulmonary disease&#58; GOLD executive summary"
                      "autores" => array:1 [
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                          "etal" => true
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                            0 => "J&#46; Vestbo"
                            1 => "S&#46;S&#46; Hurd"
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                            4 => "C&#46; Vogelmeier"
                            5 => "A&#46; Anzueto"
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                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1164/rccm.201204-0596PP"
                      "Revista" => array:6 [
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                        "link" => array:1 [
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                            "web" => "Medline"
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              "identificador" => "bib0155"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Respiratory symptoms and diagnosis of COPD in smokers of various types to tobacco&#46; Results from the IBERPOC study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "C&#46;A&#46; Jimenez-Ruiz"
                            1 => "V&#46; Sobradillo"
                            2 => "R&#46; Gabriel"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
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            2 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Salvi"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ccm.2013.09.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chest Med"
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            3 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of COPD from exposure to biomass smoke&#58; a meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            1 => "Y&#46; Zhou"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.08-2114"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
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              "identificador" => "bib0170"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Occupational exposures and the risk of COPD&#58; dusty trades revisited"
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Occupational and Biomass Exposure in COPD: Results of a Cross-Sectional Analysis of the On-Sint Study
Exposición laboral y a biomasa en la EPOC: resultados de un análisis transversal del estudio On-Sint
José Luis López-Camposa,b,
Corresponding author
lcampos@separ.es

Corresponding author.
, Alberto Fernández-Villarc, Carmen Calero-Acuñaa, Cristina Represas-Represasc, Cecilia López-Ramíreza, Virginia Leiro Fernándezc, Ricard Casamord, en nombre de los investigadores del estudio On-Sint
a Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Sevilla, Spain
b CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
c Servicio de Neumología, Instituto de Investigación Biomédica de Vigo (IBIV), Complexo Hospitalario de Vigo, Vigo, Pontevedra, Spain
d Departamento Médico, Novartis Farmacéutica, Barcelona, Spain
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Geographical distribution for &#40;a&#41; additional non-tobacco risk factors&#44; &#40;b&#41; occupational exposures&#44; and &#40;c&#41; biomass exposure&#44; in a smoking population&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic obstructive pulmonary disease &#40;COPD&#41; is characterized by persistent airflow limitation that is usually progressive and associated with exposure to noxious particles or gases&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Two key findings are needed for a diagnosis of COPD&#58; non-reversible airflow obstruction and exposure to inhaled particles or gases causing this obstruction&#46; The main inhaled gas associated with COPD is tobacco smoke&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> However&#44; other inhaled toxins have also been described as a risk factor for COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Two main substances other than tobacco have been implicated in COPD&#44; namely biomass and occupational dust or chemicals&#46; The term biomass defines the energy obtained from the combustion of organic products&#46; This combustion produces fumes that can be inhaled&#44; causing bronchial inflammation in susceptible individuals&#44; and secondary bronchial obstruction&#44; indistinguishable from COPD in many respects&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> Furthermore&#44; occupational exposure to dust&#44; gases or volatile chemicals can also cause COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">5</span></a> However&#44; it is common to find patients who besides being exposed to these substances also smoke or have smoked&#44; so it is sometimes difficult to determine to what extent each substance has contributed to the development of COPD&#59; moreover&#44; both substances have an additive risk factor for COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It is frequently reported in the literature that biomass is the most frequently inhaled substance after tobacco smoke in developing countries&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> However&#44; the frequency of exposure depends on the geographical area where it is studied&#44; since the use of biomass differs depending on the region studied&#46; In Spain&#44; biomass and occupational dust exposures have not been fully described and only 1 study has provided some information about exposure to substances other than tobacco in a population of patients with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> This study analyzes the information from the On-Sint study&#44; presents data on exposure to substances other than tobacco in this cohort of COPD patients and assesses their impact on the clinical presentation of the disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This study is a cross-sectional analysis of the On-Sint study&#46; The methodology of the On-Sint study has been extensively described elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> Briefly&#44; this is an observational&#44; nationwide&#44; real-life&#44; cohort study&#44; in which patients diagnosed with COPD were recruited between December 2011 and April 2013 by Primary Care &#40;PC&#41; and Secondary Care &#40;SC&#41; physicians&#46; Consecutive patients aged &#62;40 years who were smokers or ex-smokers with a history of &#62;10 pack-years&#44; diagnosed with COPD&#44; with a complete clinical history of respiratory symptoms&#44; able to complete the CAT questionnaire&#44; and who gave their written informed consent were selected to participate in the study&#46; Ethical approval was granted by the Institutional Review Board from Servicio Gallego de Salud &#40;SERGAS&#41; registry number 2011&#47;359&#46; In order to record real-life clinical behavior of participant doctors&#44; the only exclusion criterion considered in the study protocol was participation in any other clinical trial at the time of inclusion&#46; In addition&#44; patients with pulmonary diseases associated with occupational factors including occupational asthma&#44; hypersensitivity pneumonia or interstitial lung diseases were also excluded&#46; In order to make a real-life evaluation&#44; patients were recruited by PC and SC physicians with no matching for gender&#44; age&#44; lung function or any clinical features&#46; Sample size was calculated according to the prevalence and the degree of underdiagnosis of COPD in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a> A planned total of 1440 patients with COPD was expected to constitute a sample of 0&#46;1&#37; of the study population&#44; assuming 10&#37; of patients would have no valid information&#46; Although a uniform distribution of recruitment within the country was planned including all regions in the country&#44; the selection of participant investigators was voluntary&#44; with no attempt to achieve representative sampling&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">During the inclusion visit&#44; patients underwent a clinical evaluation&#44; which included the presence of risk factors for COPD&#44; not only tobacco smoke&#44; but also other inhaled substances&#46; Smoking history was collected&#44; including current smoking status and cumulative consumption in pack-years&#46; Occupational and biomass exposure was self-reported&#46; Patients were asked about their previous exposures&#46; In particular&#44; they were asked if they had been exposed to any other risk factor and&#44; if they replied in the affirmative&#44; the exact exposure was determined&#46; Exposure to other substances was categorized into three groups&#58; occupational dust and chemicals&#44; biomass fuels&#44; or other exposures&#46; The participating centers were classified according to the population of the locality where they were in rural &#40;&#60;<span class="elsevierStyleHsp" style=""></span>5&#44;000 inhabitants&#41;&#44; semiurban &#40;5&#44;000&#8211;19&#44;999 inhabitants&#41; and urban &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>20&#44;000 inhabitants&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The CAT questionnaire was administered to all participants in the inclusion visit&#46; The questionnaire was self-administered or administered by the investigator if any patient had reading&#44; writing or sight difficulties&#46; If more than two questions were unanswered&#44; the questionnaire was considered invalid&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical Computations</span><p id="par0035" class="elsevierStylePara elsevierViewall">Although cases were recruited by respiratory and primary care physicians&#44; all patients were followed up by general practitioners&#44; so comparison between PC and SC was impractical and would have produced confounding results&#46; Consequently&#44; all patients were analyzed together&#46; In addition&#44; since the sample was not intended to be representative of the different regions&#44; we did not compare the impact of different exposures by regions&#46; Statistical computations were performed using the Statistical Package for Social Sciences &#40;SPSS&#44; IBM Corporation Somers&#44; NY&#44; US&#41;&#44; version 20&#46;0&#46; Absolute and relative frequencies for categorical questions were used to describe variables&#44; together with the inter-regional range &#40;IRR&#41;&#44; expressing the range of the means or percentages within the different regions&#44; allowing us to further assess heterogeneity&#46; The IRR is expressed as a percentage for qualitative variables&#44; while quantitative variables are expressed by unit of measure&#46; Geographical maps were constructed using Microsoft PowerMap for Microsoft Excel 2013 &#40;Microsoft Corporation&#44; Redmond&#44; WA&#41;&#46; Bivariate analyses comparing cases with tobacco smoke as the only risk factor with those with additional risk factors were performed with the chi-squared test or the unpaired Student <span class="elsevierStyleItalic">T</span> test&#44; after checking the equality of the variances with the Levene test&#46; Variables with a <span class="elsevierStyleItalic">P</span> value &#60;&#46;1 were entered into a backward stepwise multivariate binomial logistic regression analysis with the presence of additional risk factors as the dependent variable&#46; A <span class="elsevierStyleItalic">P</span> value &#60;&#46;05 was considered significant&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">During the study period&#44; 1264 patients were included in the study&#46; Of these&#44; 50 &#40;4&#46;0&#37;&#41; patients were excluded for not fulfilling the inclusion criteria&#46; Thus&#44; the sample size of the On-Sint cohort was 1214 patients with COPD&#44; of which 857 &#40;70&#46;6&#37;&#41; were recruited by PC and 357 &#40;29&#46;4&#37;&#41; by SC physicians&#46; The frequency of the different risk factors for COPD is depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; All patients were smokers or ex-smokers as per the inclusion criteria&#46; However&#44; 1012 &#40;83&#46;4&#37;&#41; had tobacco as the only risk factor whereas 202 &#40;16&#46;6&#37;&#41; had an additional exposure&#46; The geographical distribution of this exposure is depicted in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; showing greater exposure in the northern parts of the country and on the east coast&#46; Biomass exposure was rather low&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The differences between COPD with tobacco as the only risk factor versus COPD with additional risk factors are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The main factors associated with having an added risk factor were gender&#44; age&#44; chronic sputum production&#44; the Charlson index&#44; CAT score&#44; long-term oxygen therapy&#44; short-acting &#946;<span class="elsevierStyleInf">2</span> agonists&#44; inhaled steroids&#44; and the use of mucolytics&#46; The results of the multivariate analysis including these variables are presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Male gender&#44; CAT score and rurality were associated with having an additional risk factor&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">This is the first study to show the frequency of exposure to other risk factors in addition to tobacco&#44; and the distribution within the different Spanish regions&#44; showing a greater exposure in the northern part of the country and on the east coast&#46; In addition&#44; the study shows the clinical variables associated with this exposure&#44; indicating that COPD caused by tobacco plus an additional risk factor has some similarities with traditional COPD&#44; except that it is more frequent in men&#44; has a greater impact on HRQL for a similar functional impairment&#44; and is associated with rural areas&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Various studies have provided evidence that a considerable proportion of individuals with COPD present non-tobacco risk factors&#46; The <span class="elsevierStyleItalic">Burden of Obstructive Lung Disease</span> &#40;BOLD&#41; Study evaluated data from 14 countries and found that among 4291 never smokers&#44; 6&#46;6&#37; met criteria for mild COPD&#44; and 5&#46;6&#37; met criteria for moderate to very severe disease&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> Occupational exposures leading to COPD have been described for several jobs&#46; High exposure to gases or fumes was associated with chronic bronchitis<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> and the relationship with lung function decline or chronic respiratory symptoms has been described in welders&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> agricultural workers&#44;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">13&#44;14</span></a> and different industries&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">15&#8211;17</span></a> A population-based study in north-east England investigated respiratory symptoms and the prevalence of spirometrically defined COPD between 2002 and 2004&#46; The prevalence of respiratory symptoms was 55&#37; and COPD was present in 10&#37; of subjects&#46; Interestingly&#44; COPD and respiratory symptoms were associated with occupational exposures&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a> In the USA the prevalence of COPD according to occupation has recently been reported for different occupational groups on the basis of the National Health Interview Survey Occupational Codes&#44; with a prevalence of below 5&#37; for all occupational exposures&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The impact of biomass exposure is also well documented as a risk factor for COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> Moreover&#44; an improvement in lung function and prognosis has been shown when air pollution from biomass is reduced&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">20&#44;21</span></a> However&#44; biomass is used much less in a developed country like Spain&#46; In our cohort&#44; the frequency of occupational exposure was higher than reported for biomass exposure&#46; In particular&#44; the northern part of the country is more frequently exposed than the south&#44; probably reflecting the differences in the distribution of industries throughout the country&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Our study has found some associations between additional smoke exposure and clinical characteristics&#46; The association with male gender seems obvious since in Spain the jobs involving occupational exposure are mostly performed by men&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">22</span></a> A previous cross-sectional analysis reported that COPD with exposure to vapor&#44; dust&#44; gas or fumes at any time was associated with older age&#44; male gender&#44; work-related respiratory disability&#44; current wheezing and hay fever&#44; despite similar severity of airflow obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">23</span></a> However&#44; while this is true for our community&#44; in different regions in different countries including rural areas or agricultural settings&#44; a relationship with female gender has been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">18&#44;24</span></a> In addition&#44; we found an association with a more impaired health status as measured by the CAT score&#44; suggesting a higher impact of the disease for a similar lung function&#46; Previous studies have also identified a relationship between occupational exposure and health status&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a> so our data confirm previous associations in a cohort of patients from a country with specific characteristics with regard to non-tobacco COPD risk factor exposure&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Although we were not able to find any other associations&#44; the type of COPD may also be influenced by the type of smoke&#46; Previous studies have found that female patients with wood smoke-related COPD do not appear to develop emphysema as much as individuals with tobacco-related COPD&#44; despite presenting severe airway involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a> In Mexico&#44; it has also been reported that biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure&#44; suggesting an airway-predominant phenotype&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a> Unfortunately&#44; the methodology used in the present study did not allow us to investigate these differences in the different respiratory compartments&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The CAT score is a self-administered health status questionnaire for assessing the impact of COPD on patients&#46; Different studies have demonstrated its good psychometric properties and its association with several clinically relevant outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> Accordingly&#44; CAT is able to capture part of the variability in the clinical impact of the disease which is not evaluated by lung function&#46; In this study&#44; we found that patients with additional exposures expressed a different impact of the disease as measured by CAT&#44; suggesting that COPD with other risk factors may have a more profound impact for the same lung function impairment&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Several issues must be considered for the correct interpretation of our data&#46; Occupational and biomass exposure was self-reported&#46; Various validated questionnaires are available in the literature for evaluating the different exposures in a formal occupational interview&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> However&#44; for the sake of simplicity we opted for self-reported recording of the information&#46; Similarly&#44; we recorded the history of exposure&#44; but not the intensity of this exposure&#46; A recent study has validated a biomass exposure index to quantify the amount of biomass exposure during a life-time&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a> Additionally&#44; we did not record the nature of the biomass or the different jobs&#44; which may have provided extra information&#46; Another aspect that merits consideration is that&#44; in order to make the project affordable&#44; we collected a limited number of variables for analysis&#46; Thus&#44; it is possible that future trials including a higher number of variables may yield a more comprehensive overview&#46; Finally&#44; the sample size was not estimated to allow representative geographical distribution sampling or to allow comparisons between regions&#46; Consequently&#44; the analysis did not attempt to make direct comparisons between the geographical areas within the country&#46; Nonetheless&#44; even with these limitations&#44; we believe that the information presented here represents the best updated information available on different exposures in Spain&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In summary&#44; our study shows the different distribution of exposure to other risk factors in addition to tobacco in the different Spanish regions&#44; showing a greater exposure in the northern part of the country and the east coast&#46; Our study shows the clinical variables associated with this exposure that characterize COPD caused by tobacco plus an additional risk factor&#46; The information provided here could serve as a guide to alert health planners and doctors to the potential effects of these substances and take actions to improve prevention and early diagnosis&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0090" class="elsevierStylePara elsevierViewall">This project was funded by an unrestricted grant from <span class="elsevierStyleGrantSponsor" id="gs1">Novartis Farmac&#233;utica</span>&#44; SA&#44; Spain&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of Interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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            1 => "Biomass"
            2 => "Occupational"
            3 => "Epidemiology"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Although tobacco smoke is the main risk factor for chronic obstructive pulmonary disease &#40;COPD&#41;&#44; other inhaled toxics have also been associated with the disease&#46; The present study analyzes data from exposure to these substances in a cohort of patients with COPD and assesses their impact on the clinical presentation of the disease&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This is a cross-sectional analysis of the <span class="elsevierStyleItalic">Clinical presentation&#44; diagnosis and course of chronic obstructive pulmonary disease</span> &#40;On-Sint&#41; study&#46; All patients were smokers or ex-smokers as per protocol&#46; In addition&#44; during the inclusion visit patients were enquired about their occupational and biomass exposure history&#46; The clinical features of patients with and without an added risk factor to tobacco were compared and those significant were entered in a multivariate logistic regression analysis&#44; expressed as odds ratio &#40;OR&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The sample size was 1214 patients with COPD&#44; of which 1012 &#40;83&#46;4&#37;&#41; had tobacco as the only risk factor and 202 &#40;16&#46;6&#37;&#41; had additional ones&#44; mainly 174 &#40;14&#46;3&#37;&#41; with occupational gases and 32 &#40;2&#46;6&#37;&#41; with biomass exposure&#46; The geographical distribution of this exposure showed a preference for the northern parts of the country and the East coast&#46; The biomass exposure was rather low&#46; Male gender &#40;OR&#58; 2&#46;180&#41;&#44; CAT score &#40;OR&#58; 1&#46;036&#41; and the use of long-term oxygen therapy &#40;OR&#58; 1&#46;642&#41; were associated with having an additional risk factor in the multivariate analysis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Occupational exposures are more common than biomass in Spain&#46; COPD caused by tobacco plus other inhalants has some differential features and a more impaired quality of life&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Aunque el humo del tabaco es el principal factor de riesgo de la enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41;&#44; tambi&#233;n se han relacionado con la enfermedad otros agentes t&#243;xicos inhalados&#46; El presente estudio analiza datos de la exposici&#243;n a estas sustancias y eval&#250;a su impacto sobre la presentaci&#243;n cl&#237;nica de la enfermedad en una cohorte de pacientes con EPOC&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se trata de un an&#225;lisis transversal del estudio <span class="elsevierStyleItalic">Presentaci&#243;n cl&#237;nica&#44; diagn&#243;stico y evoluci&#243;n de la enfermedad pulmonar obstructiva cr&#243;nica</span> &#40;On-Sint&#41;&#46; De conformidad con el protocolo&#44; todos los pacientes eran fumadores o exfumadores&#46; Durante la visita de inclusi&#243;n se interrog&#243; a los pacientes acerca de sus antecedentes de exposici&#243;n laboral a t&#243;xicos y a combusti&#243;n de biomasa&#46; Las caracter&#237;sticas cl&#237;nicas de los pacientes que presentaban alg&#250;n factor de riesgo adem&#225;s del tabaco se compararon con las de los pacientes que no presentaban factores de riesgo adicionales&#44; y los factores que indicaron ser significativos fueron incluidos en un an&#225;lisis de regresi&#243;n log&#237;stica multivariante&#44; expresados en oportunidades relativas &#40;<span class="elsevierStyleItalic">odds ratio</span> &#91;OR&#93;&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La muestra incluy&#243; 1&#46;214 pacientes con EPOC&#44; en 1&#46;012 &#40;83&#44;4&#37;&#41; de los cuales el tabaco era el &#250;nico factor de riesgo&#46; En 202 &#40;16&#44;6&#37;&#41; se constataron otros factores&#44; en 174 &#40;14&#44;3&#37;&#41; principalmente la exposici&#243;n a gases en el &#225;mbito laboral y en 32 &#40;2&#44;6&#37;&#41; la exposici&#243;n a combusti&#243;n de biomasa&#46; La distribuci&#243;n geogr&#225;fica de esta exposici&#243;n fue mayor en la zona norte y la costa este del pa&#237;s&#46; La exposici&#243;n a humo de biomasa fue relativamente baja&#46; El an&#225;lisis multivariante mostr&#243; asociaciones entre la presentaci&#243;n de un factor de riesgo adicional y el sexo masculino &#40;OR&#58; 2&#44;180&#41;&#44; la puntuaci&#243;n CAT &#40;OR&#58; 1&#44;036&#41; y el uso de oxigenoterapia cr&#243;nica &#40;OR&#58; 1&#44;642&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En Espa&#241;a&#44; la exposici&#243;n laboral a t&#243;xicos inhalados es m&#225;s frecuente que la exposici&#243;n a humo de biomasa&#46; La EPOC causada por el tabaco y otros productos inhalados tiene algunas caracter&#237;sticas diferenciales y provoca un mayor deterioro de la calidad de vida&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; L&#243;pez-Campos JL&#44; Fern&#225;ndez-Villar A&#44; Calero-Acu&#241;a C&#44; Represas-Represas C&#44; L&#243;pez-Ram&#237;rez C&#44; Leiro Fern&#225;ndez V&#44; et al&#46; Exposici&#243;n laboral y a biomasa en la EPOC&#58; resultados de un an&#225;lisis transversal del estudio On-Sint&#46; Arch Bronconeumol&#46; 2017&#59;53&#58;7&#8211;12&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Geographical distribution for &#40;a&#41; additional non-tobacco risk factors&#44; &#40;b&#41; occupational exposures&#44; and &#40;c&#41; biomass exposure&#44; in a smoking population&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;12&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;7 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;8 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Current smokers &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">271 &#40;26&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47 &#40;23&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobacco consumption &#40;pack-years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;1 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;4 &#40;20&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyspnea &#40;MRC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;0&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic sputum production &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">718 &#40;70&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">158 &#40;78&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exacerbations in the previous year &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Two or more exacerbations &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">637 &#40;62&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">128 &#40;63&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Comorbidities &#40;Charlson&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyslipemia &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">497 &#40;49&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">106 &#40;52&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arterial hypertension &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">620 &#40;62&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137 &#40;68&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#46;4 &#40;19&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#46;6 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#46;9 &#40;19&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;0 &#40;22&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">COPD Assessment Test &#40;points&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;9 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#46;2 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Long term oxygen therapy &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">132 &#40;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49 &#40;24&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Short-acting &#946;<span class="elsevierStyleInf">2</span> agonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">352 &#40;34&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">84 &#40;41&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;077&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Short-acting muscarinic antagonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77 &#40;7&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Long-acting &#946;<span class="elsevierStyleInf">2</span> agonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">778 &#40;76&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">152 &#40;75&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Long-acting muscarinic antagonists &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">643 &#40;63&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">132 &#40;65&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inhaled steroids &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">516 &#40;51&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">119 &#40;58&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;045&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ICS dose &#40;&#956;g&#47;day beclomethasone&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1044&#46;4 &#40;591&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1000&#46;5 &#40;591&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic steroids &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Methylxanthines &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phosphodiesterase 4 inhibitors &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">99 &#40;9&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;12&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mucolytics &#40;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">265 &#40;26&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66 &#40;32&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;069&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Crude</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Adjusted</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Odds Ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95&#37; Confidence Intervals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Odds Ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95&#37; Confidence Intervals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender &#40;male&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;419&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;545&#8211;3&#46;786&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;180&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;356&#8211;3&#46;505&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CAT score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;023&#8211;1&#46;063&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;036&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;013&#8211;1&#46;060&nbsp;\t\t\t\t\t\t\n
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