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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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Original
DOI: 10.1016/j.rce.2017.06.004
Incidencia de cáncer en pacientes ambulatorios con enfermedad pulmonar obstructiva crónica
Incidence of cancer in outpatients with chronic obstructive pulmonary disease
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J.M. Figueira Gonçalvesa,
Autor para correspondencia
juanmarcofigueira@gmail.com

Autor para correspondencia.
, R. Dorta Sáncheza, L.I. Pérez Méndezb,c, L. Pérez Negrína, I. García-Talaveraa, A. Pérez Rodrígueza, D. Díaz Péreza, P. Viña Manriquea, C. Guzmán Sáenza
a Servicio de Neumología y Cirugía Torácica, Hospital Universitario Nuestra Señora de la Candelaria (HUNSC), Santa Cruz de Tenerife, España
b Departamento de Epidemiología Clínica y Bioestadística, Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria (HUNSC) y Gerencia de Atención Primaria AP, Santa Cruz de Tenerife, España
c CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, España
Contenido relacionado
No tan extraños en un tren. Incremento de la patología neoplásica en pacientes con enfermedad pulmonar obstructiva crónica
Rev Clin Esp. 2017;217:396-710.1016/j.rce.2017.09.002
D. Márquez Medina, A. Artal Cortés

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