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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Probabilidad acumulada libre de c&#225;ncer en pacientes con enfermedad pulmonar obstructiva cr&#243;nica&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#42;</span>Edad del paciente con enfermedad pulmonar obstructiva cr&#243;nica en el momento de diagn&#243;stico de c&#225;ncer&#46; L&#237;nea discontinua&#58; GOLD<span class="elsevierStyleHsp" style=""></span>III-IV&#46; L&#237;nea continua&#58; GOLD<span class="elsevierStyleHsp" style=""></span>I-II<span class="elsevierStyleSmallCaps">&#46;</span> Log rank test&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;072&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">EPOC&#58; enfermedad pulmonar obstructiva cr&#243;nica&#59; GOLD&#58; <span class="elsevierStyleItalic">Global Initiative for Chronic Obstructive Lung Disease</span>&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El tabaquismo se ha definido como la principal causa evitable de mortalidad prematura y constituye uno de los principales problemas de salud en los pa&#237;ses desarrollados<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">1-4</span></a>&#46; Entre los componentes del tabaco destacan el amon&#237;aco&#44; la piridina&#44; el alquitr&#225;n&#44; los hidrocarburos arom&#225;ticos polic&#237;clicos o las nitrosaminas&#44; cuya combusti&#243;n libera m&#225;s de 4&#46;000 sustancias nocivas para la salud y de las cuales&#44; al menos 60 han demostrado ser carcinog&#233;nicas<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">El humo del tabaco&#44; adem&#225;s de ser el responsable del 90&#37; de los c&#225;nceres de pulm&#243;n &#40;CP&#41;&#44; ha mostrado tener una s&#243;lida relaci&#243;n con el desarrollo de c&#225;ncer en otras localizaciones&#44; incluyendo la cavidad oral&#44; laringe&#44; es&#243;fago&#44; vejiga&#44; ri&#241;&#243;n&#44; p&#225;ncreas&#44; est&#243;mago&#44; colon&#44; recto y cuello uterino<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">6-11</span></a>&#46; A los efectos carcinog&#233;nicos&#44; se a&#241;ade su papel como factor de riesgo para el desarrollo de las principales enfermedades cardiovasculares y respiratorias cr&#243;nicas&#44; destacando en este &#250;ltimo grupo patolog&#237;as como el asma bronquial&#44; las infecciones respiratorias o la enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">12&#44;13</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El CP y la EPOC parecen compartir mecanismos y factores comunes adem&#225;s del h&#225;bito tab&#225;quico<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">14-17</span></a>&#44; siendo conocido que la propia EPOC incrementa entre 3-5 veces el riesgo de desarrollar CP<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">15&#44;18-22</span></a>&#46; El grado de obstrucci&#243;n bronquial&#44; la presencia de enfisema o la propia bronquitis cr&#243;nica son factores de riesgo independientes para la aparici&#243;n de CP<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">18-29</span></a>&#46; Adem&#225;s&#44; diversos estudios han demostrado un incremento en el desarrollo de tumores extrapulmonares en los pacientes con EPOC respecto a fumadores sin obstrucci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">30-35</span></a>&#46; Si bien la toxicidad directa por productos del metabolismo del tabaco pudiera ser responsable de ello&#44; el propio proceso inflamatorio subyacente en una enfermedad cr&#243;nica como la EPOC podr&#237;a jugar un papel crucial en la carcinog&#233;nesis de diferentes &#243;rganos&#44; amplificando el proceso de mutag&#233;nesis y facilitando el crecimiento tumoral y posterior metastatizaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">7&#44;36-39</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">La incidencia de CP en pacientes con EPOC oscila entre 1&#44;4 y 16&#44;7 por 1&#46;000 personas-a&#241;o<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">19&#44;22&#44;40</span></a>&#46; Sin embargo&#44; la incidencia global de c&#225;ncer&#44; especialmente extrapulmonar&#44; no se conoce con precisi&#243;n&#46; El objetivo de este estudio fue estimar la tasa de incidencia de c&#225;ncer &#40;tanto de localizaci&#243;n pulmonar como extrapulmonar&#41; en una poblaci&#243;n con EPOC en seguimiento en una consulta ambulatoria de neumolog&#237;a&#44; as&#237; como valorar su relaci&#243;n con el grado de obstrucci&#243;n al flujo a&#233;reo&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><p id="par0025" class="elsevierStylePara elsevierViewall">Se trata de un estudio observacional prospectivo de una cohorte de pacientes con EPOC en seguimiento en las consultas de neumolog&#237;a del Hospital Universitario Nuestra Se&#241;ora de Candelaria &#40;HUNSC&#41; durante el periodo comprendido entre el 1 de enero de 2012 y el 31 de diciembre de 2015&#46; La poblaci&#243;n incluida representa el &#225;rea sur y capitalina de la isla de Tenerife&#44; que tiene una poblaci&#243;n de referencia de 452&#46;000 habitantes y 22 &#225;reas de salud&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Los criterios de inclusi&#243;n fueron&#58; edad mayor de 40 a&#241;os&#44; tabaquismo activo o estado de exfumador con un &#237;ndice paquetes-a&#241;o &#40;IPA&#41; igual o mayor que 10 y una relaci&#243;n volumen espiratorio forzado en el primer segundo &#40;FEV<span class="elsevierStyleInf">1</span>&#41;&#47;capacidad vital forzada &#40;FVC&#41; menor del 70&#37; tras la administraci&#243;n de salbutamol&#46; Los criterios de exclusi&#243;n fueron&#58; la presencia de enfermedad respiratoria cr&#243;nica por causa distinta a la EPOC&#44; el diagn&#243;stico previo de neoplasia y la presencia de obstrucci&#243;n cr&#243;nica al flujo a&#233;reo sin exposici&#243;n a humo de tabaco o con un IPA inferior a 10&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A trav&#233;s de la historia cl&#237;nica informatizada &#40;HCI&#41; se recogieron de cada paciente los siguientes par&#225;metros&#58; edad&#44; sexo&#44; &#237;ndice de masa corporal &#40;IMC&#41; &#40;peso en kg&#47;talla en m<span class="elsevierStyleSup">2</span>&#41;&#44; h&#225;bito tab&#225;quico &#40;fumador activo si hab&#237;a fumado por lo menos un cigarrillo en los &#250;ltimos 6 meses&#59; exfumador en el caso que hubiera sido fumador y mantuviera una abstinencia continuada de al menos 6 meses&#59; y no fumador si nunca hab&#237;a fumado&#41; e intensidad del mismo mediante el c&#225;lculo del IPA &#40;&#91;n&#250;mero de cigarrillos diarios<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>a&#241;os fumando&#93;&#47;20&#41;&#46; Se registraron asimismo los resultados de la espirometr&#237;a forzada&#58; FEV<span class="elsevierStyleInf">1</span>&#44; FVC y cociente FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#44; y se estratificaron a los pacientes de acuerdo con los grados de gravedad recogidos en la gu&#237;a GOLD 2009<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">41</span></a> y las categor&#237;as de la GOLD 2017<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">42</span></a>&#46; Seg&#250;n la GOLD 2009 la gravedad de la EPOC se clasifica en los siguientes estadios&#58; leve &#40;estadio<span class="elsevierStyleHsp" style=""></span>I&#41; FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>80&#37;&#59; moderado &#40;estadio<span class="elsevierStyleHsp" style=""></span>II&#41; FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; y<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80&#37;&#59; grave &#40;estadio<span class="elsevierStyleHsp" style=""></span>III&#41; FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30&#37; y<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&#37;&#59; y muy grave &#40;estadio<span class="elsevierStyleHsp" style=""></span>IV&#41; FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37;&#46; La gu&#237;a GOLD 2017 a&#241;ade a los estadios<span class="elsevierStyleHsp" style=""></span>I-IV una letra &#40;A&#44; B&#44; C&#44; D&#41; que aporta informaci&#243;n sobre los s&#237;ntomas del paciente y el riesgo de exacerbaci&#243;n&#46; As&#237; pues&#44; los grupos A y B ser&#225;n aquellos que presentan &#60;<span class="elsevierStyleHsp" style=""></span>2 exacerbaciones al a&#241;o sin ingreso hospitalario&#44; mientras que los C y D representar&#225;n a los pacientes con &#8805;<span class="elsevierStyleHsp" style=""></span>2 exacerbaciones&#47;a&#241;o y&#47;o &#8805;<span class="elsevierStyleHsp" style=""></span>1 hospitalizaci&#243;n&#46; Adem&#225;s&#44; los grupos A y C corresponden a los pacientes con disnea entre 0-1&#44; evaluada a trav&#233;s de la escala modificada del <span class="elsevierStyleItalic">Medical Research Council</span> &#40;mMRC&#41;&#44; y&#47;o que obtienen una puntuaci&#243;n inferior a 10 en el COPD <span class="elsevierStyleItalic">Assessment Test</span> &#40;CAT&#41;&#59; mientras que los grupos B y D ser&#225;n aquellos con mMRC &#8805;<span class="elsevierStyleHsp" style=""></span>2 y&#47;o puntuaciones en el CAT &#8805;<span class="elsevierStyleHsp" style=""></span>10&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Los casos incidentes de c&#225;ncer y su fecha de diagn&#243;stico durante el periodo de estudio se categorizaron para su an&#225;lisis posterior en pulmonares y extrapulmonares&#44; siendo excluidos los de origen cut&#225;neo distintos del melanoma&#46; Los diagn&#243;sticos de neoplasia fueron realizados por los diferentes especialistas del hospital&#46; Asimismo&#44; se contabilizaron los fallecimientos de la cohorte acontecidos en el periodo de estudio &#40;enero 2012-diciembre 2015&#41;&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lisis estad&#237;stico</span><p id="par0045" class="elsevierStylePara elsevierViewall">Se realiz&#243; un an&#225;lisis descriptivo inicial a trav&#233;s de la media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desviaci&#243;n est&#225;ndar &#40;DE&#41; para las variables num&#233;ricas&#44; o el porcentaje &#40;&#37;&#41; para las cualitativas&#46; Para la estimaci&#243;n puntual y por intervalos de confianza del 95&#37; &#40;IC 95&#37;&#41; de la tasa de incidencia de c&#225;ncer&#44; se utiliz&#243; como denominador el seguimiento en meses de cada paciente por el &#237;ndice persona-tiempo hasta el evento del diagn&#243;stico de neoplasia o bien hasta finalizar el periodo de seguimiento&#46; Estas tasas fueron calculadas globalmente&#44; as&#237; como por grupos &#40;C&#225;ncer pulmonar y extrapulmonar&#41;&#46; El an&#225;lisis de la incidencia de c&#225;ncer seg&#250;n las caracter&#237;sticas de los pacientes recogidas de la HCI se realiz&#243; de forma bivariada a trav&#233;s del test de Chi-cuadrado&#44; t-Student o ANOVA&#44; seg&#250;n la naturaleza de la variable &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; El an&#225;lisis multivariado se realiz&#243; mediante una regresi&#243;n log&#237;stica m&#250;ltiple &#40;modo condicional&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Para la valoraci&#243;n prospectiva del tiempo libre de enfermedad &#40;en a&#241;os&#41; hasta el diagn&#243;stico de c&#225;ncer o el final del seguimiento en diciembre 2015 se utiliz&#243; un an&#225;lisis de supervivencia&#44; expresando como concepto de supervivencia el &#171;porcentaje acumulado libre de enfermedad&#187; y siendo el evento a medir el diagn&#243;stico de c&#225;ncer &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Se emple&#243; la regresi&#243;n de Cox para el ajuste multivariado y el test de Log Rank para el contraste de las categor&#237;as de GOLD reagrupadas de forma dicot&#243;mica &#40;I&#43;II<span class="elsevierStyleHsp" style=""></span>vs&#46;<span class="elsevierStyleHsp" style=""></span>III-IV&#41;&#44; al ser las que mejor discriminaron la diferencia en el &#171;porcentaje acumulado libre de enfermedad&#187;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Todas las pruebas de contraste de hip&#243;tesis fueron bilaterales&#44; para un nivel de significaci&#243;n del 5&#37;&#46; Los an&#225;lisis se realizaron mediante el programa estad&#237;stico SPSS&#47;PC &#40;version 21&#44;0 para Windows&#59; SPSS&#44; Inc&#46;&#44; Chicago&#44; IL&#41;&#46; El estudio fue aprobado por el Comit&#233; &#201;tico del HUNSC&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0060" class="elsevierStylePara elsevierViewall">Se incluyeron 308 pacientes con EPOC&#59; 33 pacientes fallecieron y en 48 se hizo un diagn&#243;stico de c&#225;ncer durante el periodo de estudio&#44; por lo que la tasa de incidencia se estim&#243; en 10&#44;3 casos por cada 1&#46;000 EPOC-a&#241;o &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58;7&#44;6-13&#44;6 casos&#41;&#46; Los tumores m&#225;s frecuentes fueron el CP &#40;31&#37;&#41;&#44; tumores del tracto genitourinario &#40;29&#37;&#41;&#44; digestivo &#40;21&#37;&#41;&#44; cabeza&#47;cuello &#40;6&#37;&#41; y un grupo miscel&#225;neo &#40;12&#44;5&#37;&#41;&#46; En funci&#243;n de la localizaci&#243;n&#44; la incidencia anual para CP fue de 3&#44;4 casos por cada 1&#46;000 EPOC-a&#241;o &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58;1&#44;9-5&#44;6 casos&#41;&#44; y para tumores de localizaci&#243;n extrapulmonar de 7&#44;3 casos por cada 1&#46;000 EPOC-a&#241;o &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58; 5-10 casos&#41;&#59; dichos valores reflejan una raz&#243;n de tasas de incidencia de 2&#44;14 &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58;1&#44;16-3&#44;94&#41; a favor de las neoplasias de origen extrapulmonar &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;017&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Las caracter&#237;sticas cl&#237;nicas y demogr&#225;ficas de la serie&#44; as&#237; como los contrastes de an&#225;lisis bivariado transversal se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#44; detect&#225;ndose que aquellos pacientes con mayor IPA presentaron un mayor n&#250;mero de diagn&#243;sticos de c&#225;ncer&#44; sin detectarse diferencias significativas en el resto de las variables&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">En el an&#225;lisis de regresi&#243;n log&#237;stica multivariado se objetiv&#243; un aumento significativo del riesgo promedio de c&#225;ncer al agrupar sujetos con obstrucci&#243;n leve y moderada seg&#250;n la clasificaci&#243;n de la GOLD 2009 &#40;grados<span class="elsevierStyleHsp" style=""></span>I y II&#41; con respecto a obstrucciones m&#225;s graves &#40;grados III y IV&#41;&#44; as&#237; como en aquellos con mayor consumo de tabaco acumulado&#44; quedando excluidas de la ecuaci&#243;n el resto de las variables&#46; La estimaci&#243;n de OR ajustado se muestra en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>A&#46; La valoraci&#243;n prospectiva de la incidencia &#40;an&#225;lisis longitudinal-regresi&#243;n de Cox&#41; reforz&#243; estas asociaciones al mostrar igualmente una diferencia significativa en la probabilidad acumulada libre de c&#225;ncer&#58; aquellos sujetos agrupados con obstrucci&#243;n leve y moderada&#44; o con mayor IPA&#44; presentaron una mayor incidencia de c&#225;ncer &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>B&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discusi&#243;n</span><p id="par0075" class="elsevierStylePara elsevierViewall">En esta cohorte de pacientes diagnosticados de EPOC&#44; la incidencia de c&#225;ncer de cualquier localizaci&#243;n fue de 10&#44;3 casos por cada 1&#46;000 pacientes EPOC-a&#241;o&#44; siendo la incidencia de neoplasias extrapulmonares el doble de las de localizaci&#243;n primaria pulmonar&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">La asociaci&#243;n entre CP y EPOC se encuentra claramente establecida<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">15-29</span></a>&#46; La elevada prevalencia de CP en la EPOC sugiere que pueden existir mecanismos comunes en ambas enfermedades&#46; Estos incluir&#237;an factores gen&#233;ticos&#44; epigen&#233;ticos&#44; inflamatorios y la propia alteraci&#243;n estructural del pulm&#243;n en la EPOC que favorecer&#237;an el desarrollo de neoplasias malignas&#44; m&#225;s all&#225; del propio efecto nocivo del humo del tabaco<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">17&#44;38&#44;40</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">La incidencia de CP en paciente con EPOC oscila entre el 1&#44;4 y 16&#44;7 por 1&#46;000 personas-a&#241;o<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">19&#44;22&#44;40</span></a>&#44; coincidiendo nuestros resultados con lo publicado en el <span class="elsevierStyleItalic">Lung Health Study</span><a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">19</span></a>&#46; Si comparamos nuestra serie con estudios similares en poblaci&#243;n espa&#241;ola&#44; la incidencia result&#243; inferior a lo descrito por de Torres et al&#46; en una serie previa<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">22</span></a>&#44; lo cual puede ser reflejo del mayor consumo de tabaco &#40;IPA medio de 74&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#44;9&#41; reportado en esta &#250;ltima&#46; En el <span class="elsevierStyleItalic">Cancer Prevention Study</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">II</span><a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">43</span></a> se demostr&#243; que fumar un paquete de cigarrillos al d&#237;a durante 30 a&#241;os aumentaba la mortalidad espec&#237;fica por CP un 20-40&#37; en varones y un 14-20&#37; en mujeres&#44; en comparaci&#243;n con las personas que nunca hab&#237;an fumado&#46; El riesgo pr&#225;cticamente se duplica si el consumo se mantiene durante m&#225;s de 40 a&#241;os<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">44</span></a>&#46; Doll y Peto<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">45</span></a> desarrollaron un modelo cuantitativo de riesgo de CP en el que la duraci&#243;n del h&#225;bito tab&#225;quico resultaba ser un factor m&#225;s significativo que el n&#250;mero de cigarrillos fumados en individuos con un consumo de paquetes-a&#241;o comparable&#46; En ese modelo&#44; la relaci&#243;n entre el n&#250;mero de cigarrillos fumados al d&#237;a y el riesgo de CP era relativamente lineal&#46; Sin embargo&#44; la duraci&#243;n del consumo de tabaco mostraba un incremento exponencial del riesgo de CP&#46; En consonancia con estos datos&#44; se ha encontrado una relaci&#243;n entre el IPA y el desarrollo de mutaciones en diferentes &#243;rganos diana que favorecer&#237;an no s&#243;lo el desarrollo de CP&#44; sino tambi&#233;n de tumores a nivel extrapulmonar como son el c&#225;ncer de vejiga&#44; colon o laringe entre otros<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">7</span></a>&#46; Estos resultados son acordes a los hallazgos de nuestro estudio&#44; en el que la incidencia global de c&#225;ncer fue mayor en aquellos pacientes con EPOC que presentaban un IPA m&#225;s elevado&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Es llamativa la alta incidencia de tumores de localizaci&#243;n extrapulmonar en nuestro estudio&#44; en especial en pacientes EPOC con obstrucci&#243;n al flujo a&#233;reo leve-moderada&#46; Nakayama et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">30</span></a> investigaron el desarrollo de c&#225;ncer en 127 pacientes con EPOC frente a sujetos fumadores sin obstrucci&#243;n&#46; Los pacientes con EPOC presentaron un riesgo relativo de c&#225;ncer de 2&#44;2 &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58; 1&#44;24-4&#44;27&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0069&#41; frente a los sujetos control&#44; siendo los tumores m&#225;s frecuentes los de pulm&#243;n&#44; cabeza&#47;cuello y tracto urinario&#46; En esta l&#237;nea&#44; Purdue et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a> evaluaron el riesgo de c&#225;ncer en trabajadores de la construcci&#243;n diagnosticados de EPOC&#44; encontr&#225;ndose un incremento de 2&#44;2 &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58; 1&#44;8-2&#44;7&#41; en el riesgo de CP y de 1&#44;6 &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58; 1&#44;4-2&#44;0&#41; en el de localizaci&#243;n extrapulmonar&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Chiang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">32</span></a> demostraron que en los pacientes con EPOC existe un mayor riesgo de desarrollar determinados tumores como son de cabeza y cuello&#44; es&#243;fago&#44; pulm&#243;n&#44; mama&#44; pr&#243;stata&#44; sistema nervioso central&#44; linfoma y mieloma m&#250;ltiple&#46; En nuestra cohorte&#44; las neoplasias extrapulmonares m&#225;s frecuentes fueron el c&#225;ncer colorrectal y el c&#225;ncer de pr&#243;stata&#46; Si bien su incidencia en poblaci&#243;n general aumenta a partir de los 50 a&#241;os&#44; lo cual podr&#237;a sesgar los resultados dada la edad media de nuestra serie&#44; diversos estudios han demostrado que en los pacientes con EPOC estos tumores son m&#225;s frecuentes que en la poblaci&#243;n general<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">32-34</span></a>&#46; Los pacientes con EPOC tienen mayor riesgo de presentar c&#225;ncer de pr&#243;stata &#40;<span class="elsevierStyleItalic">hazard ratio</span> de 4&#44;9&#59; IC<span class="elsevierStyleInf">95&#37;</span>&#58;1&#44;8-13&#44;5&#41; que los sujetos sin obstrucci&#243;n bronquial<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a>&#46; Aunque en la EPOC existe una disminuci&#243;n de los niveles de testosterona&#44; su relaci&#243;n con el desarrollo de c&#225;ncer de pr&#243;stata no est&#225; establecida<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">34&#44;46</span></a>&#46; Algunos factores como la obesidad&#44; la inactividad f&#237;sica &#40;circunstancias habitualmente presentes en pacientes con EPOC&#41; y el tipo de dieta parecen ser elementos comunes para el desarrollo de c&#225;ncer colorrectal y pulmonar<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">17&#44;47&#44;48</span></a>&#46; Chun et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">35</span></a> encontraron que los pacientes con EPOC ten&#237;an un incremento del riesgo de presentar p&#243;lipos colorrectales frente a sujetos sin obstrucci&#243;n &#40;OR de 2&#44;1 &#91;IC<span class="elsevierStyleInf">95&#37;</span>&#58; 1&#44;1-3&#44;8&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;019&#41;&#44; por lo que los autores recomendaban la realizaci&#243;n peri&#243;dica de colonoscopias en dichos sujetos para detectar lesiones premalignas&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">En nuestro an&#225;lisis la incidencia de c&#225;ncer de localizaci&#243;n extrapulmonar duplica la incidencia de CP&#44; siendo destacable el porcentaje de pacientes que desarrollaron c&#225;ncer colorrectal&#44; de pr&#243;stata y vejiga&#46; Una explicaci&#243;n razonable que justificar&#237;a este hecho&#44; m&#225;s all&#225; del propio da&#241;o generado por las sustancias cancer&#237;genas del tabaco&#44; podr&#237;a ser la existencia de una inflamaci&#243;n sist&#233;mica de bajo grado asociada a la EPOC&#46; Sabemos que existen una serie de mol&#233;culas claves en el proceso patog&#233;nico que vincula la inflamaci&#243;n con la carcinog&#233;nesis&#44; tales como las integrinas&#44; el factor transformador de crecimiento beta&#44; el factor de transcripci&#243;n kappa beta &#40;NF-kB&#41;&#44; el transductor de se&#241;al y activador de la transcripci&#243;n 3 &#40;STAT-3&#41;&#44; el factor de necrosis tumoral alfa &#40;TNF-alfa&#41; y la ciclooxigenasa-2<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">36-39</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Es destacable que los sujetos m&#225;s propensos a desarrollar c&#225;ncer fueran aquellos con estadios m&#225;s leves de la enfermedad&#46; Es posible que ello se deba a un sesgo de supervivencia&#44; en donde los pacientes con EPOC m&#225;s grave podr&#237;an carecer de los factores predisponentes para el desarrollo de c&#225;ncer&#44; alcanzando as&#237; fases m&#225;s evolucionadas de la enfermedad<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">49</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Este estudio tiene varias limitaciones&#46; En primer lugar&#44; la poblaci&#243;n estudiada pertenec&#237;a a un &#250;nico hospital y el tama&#241;o muestral fue limitado&#46; Evidentemente&#44; una muestra mayor podr&#237;a haber mostrado diferencias no detectadas en el an&#225;lisis actual&#46; Ser&#237;a de indudable inter&#233;s reclutar una muestra mayor representativa de los pacientes con EPOC de todo el archipi&#233;lago canario&#46; En segundo lugar&#44; es posible haber incurrido en un sesgo de informaci&#243;n debido a la obtenci&#243;n de las variables desde la historia cl&#237;nica de los pacientes&#44; aunque la estandarizaci&#243;n actual de los criterios diagn&#243;sticos minimiza esta posibilidad&#46; En tercer lugar&#44; no dispusimos de un grupo control de poblaci&#243;n general o fumadores sin obstrucci&#243;n&#44; por lo que no podemos descartar alg&#250;n factor que pudiera explicar el elevado n&#250;mero de neoplasias no pulmonares de la cohorte&#46; Por &#250;ltimo&#44; se debe tener en cuenta la limitaci&#243;n propia de un estudio de base no poblacional&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; los pacientes EPOC con un grado de obstrucci&#243;n al flujo a&#233;reo leve-moderado &#40;I y II de la GOLD 2009&#41; tienen mayor riesgo de desarrollar c&#225;ncer en diversas localizaciones frente a aquellos con una obstrucci&#243;n m&#225;s avanzada&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicto de intereses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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    "resumen" => array:2 [
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La relaci&#243;n entre la enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41; y la incidencia global de c&#225;ncer es poco conocida&#46; El objetivo del estudio fue analizar la incidencia de c&#225;ncer &#40;tanto de localizaci&#243;n pulmonar como extrapulmonar&#41; en pacientes con EPOC en seguimiento en una consulta ambulatoria especializada&#44; as&#237; como valorar su relaci&#243;n con el grado de obstrucci&#243;n al flujo a&#233;reo&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Metodolog&#237;a</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional prospectivo de una cohorte de 308 pacientes con EPOC en seguimiento en consultas ambulatorias de neumolog&#237;a durante el periodo comprendido entre enero de 2012 y diciembre de 2015&#46; Las neoplasias diagnosticadas en este periodo se dividieron en pulmonares y extrapulmonares&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Las tasas de incidencia global de c&#225;ncer&#44; de c&#225;ncer de pulm&#243;n &#40;CP&#41; y de c&#225;ncer extrapulmonar fueron de 10&#44;3&#44; 3&#44;4 y 7&#44;3 casos por 1&#46;000 pacientes EPOC-a&#241;o&#44; respectivamente&#46; Los tumores m&#225;s frecuentes fueron el CP &#40;31&#37;&#41;&#44; los del tracto genitourinario &#40;29&#37;&#41; y digestivo &#40;21&#37;&#41;&#46; Los estadios leve-moderado &#40;grados<span class="elsevierStyleHsp" style=""></span>I-II de la GOLD 2009&#41; y el incremento del &#237;ndice paquetes-a&#241;o &#40;IPA&#41; se relacionaron con un aumento en la aparici&#243;n de neoplasias con un odds ratio &#40;OR&#41; de 2&#44;16 &#40;intervalo de confianza al 95&#37; &#91;IC<span class="elsevierStyleInf">95&#37;&#93;</span>&#58; 1&#44;087-4&#44;309&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&#41; y 1&#44;01 &#40;IC<span class="elsevierStyleInf">95&#37;</span>&#58;1&#44;002-1&#44;031&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41;&#44; respectivamente&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusi&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La incidencia de c&#225;ncer de localizaci&#243;n extrapulmonar en pacientes con EPOC duplica a la de CP&#46; Los estadios<span class="elsevierStyleHsp" style=""></span>I-II de la GOLD 2009 y el IPA se relacionan de forma significativa con la aparici&#243;n de neoplasias&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The relationship between chronic obstructive pulmonary disease &#40;COPD&#41; and the overall incidence of cancer is poorly understood&#46; The aim of this study was to analyse the incidence of cancer &#40;pulmonary or extrapulmonary&#41; in patients with COPD during follow-up in a specialised outpatient unit&#44; as well as to assess its relationship with the degree of airflow obstruction&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methodology</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A prospective observational study was conducted with a cohort of 308 patients with COPD in pulmonology outpatient follow-up consultations from January 2012 to December 2015&#46; The diagnosed malignancies during this period were divided into pulmonary and extrapulmonary&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The overall incidence rate of cancer&#44; lung cancer and extrapulmonary cancer were 10&#46;3&#44; 3&#46;4 and 7&#46;3 cases per 1&#44;000 patients with COPD per year&#44; respectively&#46; The most common cancers were lung cancer &#40;31&#37;&#41;&#44; genitourinary tract cancer &#40;29&#37;&#41; and gastrointestinal cancer &#40;21&#37;&#41;&#46; Mild-moderate stages &#40;grade<span class="elsevierStyleHsp" style=""></span>I-II of the 2009 GOLD classification&#41; and the increase in the pack-year index &#40;PYI&#41; were related to an increase in the onset of malignancies&#44; with an odds ratio &#40;OR&#41; of 2&#46;16 &#40;95&#37; confidence interval &#91;95&#37; CI&#93;&#58; 1&#46;087-4&#46;309&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;026&#41; and 1&#46;01 &#40;95&#37; CI&#58; 1&#46;002-1&#46;031&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;023&#41;&#44; respectively&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The incidence of extrapulmonary cancer in patients with COPD was twice that of lung cancer&#59; stages<span class="elsevierStyleHsp" style=""></span>I-II of the 2009 GOLD classification and the PYI were significantly related to the onset of malignancies&#46;</p></span>"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Probabilidad acumulada libre de c&#225;ncer en pacientes con enfermedad pulmonar obstructiva cr&#243;nica&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#42;</span>Edad del paciente con enfermedad pulmonar obstructiva cr&#243;nica en el momento de diagn&#243;stico de c&#225;ncer&#46; L&#237;nea discontinua&#58; GOLD<span class="elsevierStyleHsp" style=""></span>III-IV&#46; L&#237;nea continua&#58; GOLD<span class="elsevierStyleHsp" style=""></span>I-II<span class="elsevierStyleSmallCaps">&#46;</span> Log rank test&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;072&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">EPOC&#58; enfermedad pulmonar obstructiva cr&#243;nica&#59; GOLD&#58; <span class="elsevierStyleItalic">Global Initiative for Chronic Obstructive Lung Disease</span>&#46;</p>"
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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">p&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" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Edad&#44; a&#241;os &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Sexo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;651&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Var&#243;n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mujer &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">IMC &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;846&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">IMC</span> &#8805;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">30 &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;402&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Tabaquismo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;070&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exfumador &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fumador activo &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">IPA&#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;047&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">IPA</span> &#8805;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">60 &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;275&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Funci&#243;n pulmonar</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#44;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;302&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&#47;FVC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;455&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;831&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;494&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">GOLD 2009</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>I&#46; Leve &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>II&#46; Moderado &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>III&#46; Grave &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IV&#46; Muy grave &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">GOLD 2017</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;652&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">I &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">II &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">III &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">IV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas cl&#237;nicas y demogr&#225;ficas de los pacientes con enfermedad pulmonar obstructiva cr&#243;nica</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">GOLD&#58; <span class="elsevierStyleItalic">Global Initiative for Obstructive Lung Disease</span>&#59; IC<span class="elsevierStyleInf">95&#37;</span>&#58; intervalo de confianza al 95&#37;&#46;</p>"
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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">IC<span class="elsevierStyleInf">95&#37;</span> Odds ratio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">A&#46; An&#225;lisis transversal</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>GOLD 2009<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">B&#46; An&#225;lisis longitudinal</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>GOLD 2009<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;112-3&#44;963&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#205;ndice paquetes-a&#241;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
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              "identificador" => "tblfn0005"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Obstrucci&#243;n leve&#47;moderada &#40;I-II&#41; categor&#237;a de riesgo&#46;</p>"
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              "identificador" => "tblfn0010"
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          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Factores que incrementan el riesgo de c&#225;ncer en pacientes con enfermedad pulmonar obstructiva cr&#243;nica</p>"
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    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:49 [
            0 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Department of Health and Human Services&#46; Reducing the health consequences of smoking&#58; 25 years of progress&#46; A report of the Surgeon General&#46; DHHS &#40;CDC&#41; 89-8411&#46; Rockville&#58; U&#46;S&#46; Department of Health and Human Services&#59; 1989&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions&#44; 1990-2010&#58; A systematic analysis for the Global Burden of Disease Study 2010"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;S&#46; Lim"
                            1 => "T&#46; Vos"
                            2 => "A&#46;D&#46; Flaxman"
                            3 => "G&#46; Danaei"
                            4 => "K&#46; Shibuya"
                            5 => "H&#46; Adair-Rohani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)61766-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2012"
                        "volumen" => "380"
                        "paginaInicial" => "2224"
                        "paginaFinal" => "2260"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23245609"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cigarette smoking and lung cancer &#8212; relative risk estimates for the major histological types from a pooled analysis of case-control studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Pesch"
                            1 => "B&#46; Kendzia"
                            2 => "P&#46; Gustavsson"
                            3 => "K&#46;H&#46; J&#246;ckel"
                            4 => "G&#46; Johnen"
                            5 => "H&#46; Pohlabeln"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ijc.27339"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cancer&#46;"
                        "fecha" => "2012"
                        "volumen" => "131"
                        "paginaInicial" => "1210"
                        "paginaFinal" => "1219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22052329"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of cigarette smoking on cancer risk in the European prospective investigation into cancer and nutrition study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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