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Sin embargo&#44; desde hace ya varias d&#233;cadas&#44; se reconoce que la afectaci&#243;n precoz de las peque&#241;as v&#237;as a&#233;reas desempe&#241;a un importante papel patog&#233;nico<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">3&#44;4</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Diversos estudios han explorado a fumadores que todav&#237;a no han desarrollado LFA mediante tomograf&#237;a computarizada &#40;TC&#41;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; Sin embargo&#44; este procedimiento no permite evaluar directamente las peque&#241;as v&#237;as a&#233;reas&#44; sino que analiza la pared de bronquiolos de mayor tama&#241;o o la probable repercusi&#243;n de la disfunci&#243;n de las peque&#241;as v&#237;as &#40;DPV&#41; sobre la atenuaci&#243;n del par&#233;nquima pulmonar<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a>&#46; Frente a ello&#44; la oscilaci&#243;n forzada u oscilometr&#237;a de impulsos &#40;IOS&#41; proporciona una evaluaci&#243;n funcional espec&#237;fica de las peque&#241;as v&#237;as a&#233;reas&#44; adecuadamente sistematizada y con un patr&#243;n de afectaci&#243;n caracter&#237;stico de la DPV<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8&#44;9</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os&#44; se ha reconocido que los fumadores sin LFA constituyen un grupo heterog&#233;neo con diferentes manifestaciones sintom&#225;ticas y repercusi&#243;n sobre la calidad de vida relacionada con la salud &#40;CVRS&#41;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11</span></a>&#46; Sin embargo&#44; se dispone de poca informaci&#243;n sobre par&#225;metros funcionales o morfol&#243;gicos que puedan discriminar a dichos fumadores y&#44; en cierto modo&#44; contribuir a su afectaci&#243;n sintom&#225;tica&#46; Dada su potencial relevancia patog&#233;nica&#44; resulta atractivo considerar que la presencia de DPV podr&#237;a constituir un paso previo al desarrollo de LFA<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> y mostrar incipientes repercusiones sobre la calidad de vida&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Por tanto&#44; establecemos como hip&#243;tesis que los fumadores sin LFA tienen una peor calidad de vida cuando han desarrollado DPV&#46; Nuestro objetivo principal ha sido comparar la calidad de vida de fumadores sin LFA pero con evidencia de DPV mediante IOS con la de no fumadores&#44; fumadores sin DPV y fumadores con LFA compatible con EPOC&#46; Como objetivos secundarios hemos pretendido determinar la frecuencia de DPV en fumadores sin LFA y comparar las densidades de atenuaci&#243;n del par&#233;nquima pulmonar entre los 4 grupos de sujetos&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sujetos del estudio</span><p id="par0025" class="elsevierStylePara elsevierViewall">En las consultas de deshabituaci&#243;n tab&#225;quica de nuestro centro&#44; se seleccionaron de forma consecutiva 53 fumadores activos sin evidencia de LFA y 20 fumadores activos con LFA compatible con EPOC&#46; En ambos casos&#44; los sujetos deb&#237;an tener de 40 a 70 a&#241;os y un consumo de tabaco acumulado medio de al menos 20 paquetes<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>a&#241;o&#46; Como grupo control&#44; se seleccionaron 20 sujetos de 40 a 70 a&#241;os del grupo de referencia de nuestro laboratorio&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica de Investigaci&#243;n del Hospital Universitario La Paz &#40;PI-1261&#41; y todos los participantes firmaron su consentimiento informado&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">En el <a class="elsevierStyleCrossRef" href="#sec0060">material suplementario</a> se proporciona informaci&#243;n m&#225;s detallada de los criterios de selecci&#243;n y de los procedimientos realizados&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Determinaciones</span><p id="par0035" class="elsevierStylePara elsevierViewall">La CVRS fue evaluada mediante la autoadministraci&#243;n de la versi&#243;n espa&#241;ola de los cuestionarios gen&#233;ricos <span class="elsevierStyleItalic">Short Form 36 Health Survey</span> &#40;SF-36&#41; y <span class="elsevierStyleItalic">European Quality of Life-5 Dimensions</span> &#40;EQ-5D&#41;&#44; y en los fumadores se utilizaron los test de Fagerstr&#246;m y Glover-Nilsson&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Se realiz&#243; una TC de t&#243;rax de alta resoluci&#243;n volum&#233;trica&#44; en inspiraci&#243;n y espiraci&#243;n m&#225;ximas&#44; mediante un equipo de 16 detectores &#40;Somatom Emotion 16&#44; Siemens Medical Solutions&#44; Erlangen&#44; Alemania&#41;&#46; Mediante un programa de an&#225;lisis semiautom&#225;tico &#40;Software syngo InSpace4D&#44; Siemens&#41;&#44; se determin&#243;&#44; tanto en inspiraci&#243;n como en espiraci&#243;n m&#225;ximas&#44; la densidad pulmonar media &#40;MLD&#41;&#44; el porcentaje de v&#243;xeles con valores de atenuaci&#243;n por debajo de &#8722;950 unidades Hounsfield &#40;UH&#41; &#40;LAV&#41; o entre &#8722;1&#46;000 y &#8722;951 UH &#40;subrango 1&#41; y los umbrales de atenuaci&#243;n correspondientes al percentil 15 &#40;P15&#41;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Todas las pruebas de funci&#243;n respiratoria fueron llevadas a cabo por una &#250;nica investigadora &#40;CGQ&#41; con un equipo MasterScreen &#40;Viasys Healthcare&#44; W&#252;rzburg&#44; Alemania&#41;&#46; La IOS se realiz&#243; seg&#250;n las recomendaciones vigentes<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a>&#46; Se solicit&#243; a los participantes que&#44; con una pinza nasal y sentados con la cabeza en una posici&#243;n neutral&#44; respiraran a volumen corriente con los labios sellados alrededor de una boquilla mientras apretaban firmemente sus mejillas con las manos&#46; Al menos&#44; se realizaron 3 registros aceptables &#40;valores de coherencia a 5 y 20<span class="elsevierStyleHsp" style=""></span>Hz<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#44;7 y 0&#44;9&#44; respectivamente&#41; con una duraci&#243;n de 30 segundos&#44; utilizando para el an&#225;lisis el promedio de 3 pruebas aceptables y repetibles &#40;variabilidad &#60;<span class="elsevierStyleHsp" style=""></span>10&#37;&#41;&#46; Como &#237;ndices de resistencia total y proximal de las v&#237;as a&#233;reas&#44; se utilizaron las resistencias respiratorias a 5 y 20<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5 y R20&#41;&#44; mientras que la ca&#237;da en la resistencia de 5 a 20<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5-R20&#41; fue considerada un indicador de la resistencia de las v&#237;as a&#233;reas perif&#233;ricas&#46; Adem&#225;s&#44; se determin&#243; la reactancia a 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;X5&#41; y el &#237;ndice de &#225;rea de reactancia de baja frecuencia &#40;AX&#41; como indicadores de la funci&#243;n de las v&#237;as respiratorias perif&#233;ricas&#46; Los datos obtenidos fueron interpretados en funci&#243;n de los valores de referencia europeos de Oostveen<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a>&#46; Inmediatamente despu&#233;s&#44; se realiz&#243; una espirometr&#237;a pre- y posbroncodilatador&#44; seg&#250;n la normativa vigente<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a>&#44; utilizando los valores de referencia <span class="elsevierStyleItalic">GLI</span><a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clasificaci&#243;n de los pacientes</span><p id="par0050" class="elsevierStylePara elsevierViewall">Se defini&#243; LFA compatible con EPOC un FEV<span class="elsevierStyleInf">1</span>&#47;FVC posbroncodilatador menor del l&#237;mite inferior de la normalidad<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a>&#46; La DPV fue definida por la presencia de una R5&#44; R5-R20 y AX mayores de su l&#237;mite superior de la normalidad<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a>&#46; En ausencia de LFA y DPV&#44; los sujetos fueron considerados control&#46; Seg&#250;n estos criterios&#44; los sujetos del estudio fueron clasificados en 4 grupos mutuamente excluyentes&#58; no fumadores control&#44; fumadores sin DPV&#44; fumadores con DPV y fumadores con LFA &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Por &#250;ltimo&#44; los pacientes con LFA fueron clasificados por gravedad&#44; grupo de riesgo y fenotipo de EPOC&#44; seg&#250;n las recomendaciones vigentes<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0055" class="elsevierStylePara elsevierViewall">La estimaci&#243;n del tama&#241;o muestral se realiz&#243; en funci&#243;n de una puntuaci&#243;n del componente f&#237;sico del cuestionario SF-36 de 49&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;7 obtenida en un estudio piloto en fumadores sin LFA &#40;datos no publicados&#41;&#46; Para detectar una diferencia de al menos 5 unidades&#44; mediante contraste bilateral&#44; con un riesgo alfa de 0&#44;05 y un riesgo beta de 0&#44;10&#44; se necesitar&#237;an 20 sujetos por cada grupo&#46; Seg&#250;n un estudio previo que refiri&#243; una prevalencia de DPV del 26&#44;3&#37; entre fumadores o exfumadores con cardiopat&#237;a isqu&#233;mica&#44; alcanzando el 38&#37; en fumadores activos<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a>&#44; para obtener 2 subgrupos de fumadores sin LFA comparables seg&#250;n la existencia o no de DPV&#44; se necesitar&#237;an 53 sujetos&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Los datos se presentan como n&#250;mero &#40;porcentaje&#41; o media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desviaci&#243;n est&#225;ndar&#44; seg&#250;n sus caracter&#237;sticas y una vez comprobado su ajuste a la distribuci&#243;n normal&#44; mediante la prueba de Shapiro-Wilk&#46; Para las comparaciones entre grupos se utiliz&#243; la prueba de chi-cuadrado y el an&#225;lisis de varianza con comparaciones m&#250;ltiples post-hoc mediante la prueba de Bonferroni&#46; La relaci&#243;n entre variables fue evaluada utilizando el an&#225;lisis de correlaci&#243;n de Pearson&#46; Aquellas variables que alcanzaron una relaci&#243;n significativa fueron introducidas en un an&#225;lisis de regresi&#243;n lineal m&#250;ltiple&#44; que utiliz&#243; el m&#233;todo de pasos escalonados hacia delante&#46; Un valor de p menor de 0&#44;05 fue considerado significativo y todos los an&#225;lisis fueron realizados con el programa SPSS 15&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; EE&#46;<span class="elsevierStyleHsp" style=""></span>UU&#46;&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><p id="par0065" class="elsevierStylePara elsevierViewall">Seg&#250;n los criterios establecidos&#44; fueron reclutados 20 sujetos no fumadores&#44; 53 fumadores activos sin LFA y 20 fumadores activos con LFA compatible con EPOC &#40;<a class="elsevierStyleCrossRef" href="#sec0060">tabla S1 del material suplementario</a>&#41;&#46; Los tres grupos resultaron homog&#233;neos en sexo&#44; edad&#44; talla&#44; peso e &#237;ndice de masa corporal &#40;<a class="elsevierStyleCrossRef" href="#sec0060">tabla S2 del material suplementario</a>&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">En el grupo de fumadores sin LFA&#44; se evidenci&#243; DPV en 19 sujetos&#44; lo que supone una frecuencia del 35&#44;8&#37; &#40;IC95&#37;&#58; 22&#44;9-48&#44;81&#37;&#41;&#46; En ning&#250;n sujeto del grupo de no fumadores se evidenci&#243; DPV&#44; por lo que todos fueron considerados como sujetos control&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#44; se muestran las caracter&#237;sticas antropom&#233;tricas y de consumo de tabaco de los 4 grupos finalmente constituidos&#46; Los par&#225;metros antropom&#233;tricos resultaron similares y no se apreciaron diferencias en las caracter&#237;sticas del consumo de tabaco&#44; dependencia de la nicotina ni dependencia psicol&#243;gica&#44; social o gestual entre los fumadores&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Al margen de las l&#243;gicas diferencias en las variables de la oscilaci&#243;n forzada utilizadas para definir los grupos&#44; los &#250;nicos par&#225;metros espirom&#233;tricos que resultaron menores en los fumadores con DPV que en los fumadores sin DPV fueron el FEF<span class="elsevierStyleInf">25&#37;</span> y el FEF<span class="elsevierStyleInf">25-75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">La afectaci&#243;n morfol&#243;gica del par&#233;nquima pulmonar evidenci&#243; una menor densidad de atenuaci&#243;n en los fumadores con LFA con respecto a los otros 3 grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46; Tanto en inspiraci&#243;n como en espiraci&#243;n&#44; los pacientes con EPOC mostraban una menor densidad pulmonar media&#44; mayores porcentajes de volumen de baja atenuaci&#243;n y vol&#250;menes de atenuaci&#243;n de entre &#8722;1&#46;000 a &#8722;951<span class="elsevierStyleHsp" style=""></span>UH y de entre &#8722;950 a &#8722;901<span class="elsevierStyleHsp" style=""></span>UH&#44; as&#237; como un menor P15&#46; Sin embargo&#44; no se detectaron diferencias en las densidades de atenuaci&#243;n entre fumadores con o sin DPV&#46; A su vez&#44; tampoco se evidenci&#243; relaci&#243;n alguna entre las medidas de atenuaci&#243;n del par&#233;nquima pulmonar y las variables de oscilaci&#243;n forzada en los 2 grupos de fumadores sin LFA&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> muestra la comparaci&#243;n de la CVRS entre los 4 grupos del estudio&#46; Adem&#225;s de las previsibles diferencias entre fumadores con LFA y los otros grupos&#44; resulta interesante destacar que los fumadores con DPV tienen una peor puntuaci&#243;n en las escalas componente f&#237;sico y componente mental del cuestionario SF-36 y en el term&#243;metro del cuestionario EQ-5D&#44; tanto con respecto a los controles no fumadores como a los fumadores sin DPV&#44; lo que evidencia una situaci&#243;n intermedia de deterioro de la calidad de vida entre estos sujetos y los fumadores con EPOC &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 2</a>&#41;&#46; El an&#225;lisis de los distintos dominios del cuestionario SF-36 muestra un comportamiento similar&#44; que afecta principalmente a los dominios relacionados con el componente f&#237;sico &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> y <a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">En los fumadores sin LFA&#44; tanto con DPV como sin ella&#44; no se hall&#243; relaci&#243;n alguna entre la CVRS y las caracter&#237;sticas antropom&#233;tricas&#44; edad de inicio&#44; intensidad del consumo de tabaco&#44; a&#241;os de tabaquismo ni con las puntuaciones de los test de Fagerstr&#246;m o Glover-Nilsson&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la calidad de vida de estos sujetos se relacion&#243; con diversos par&#225;metros funcionales y morfol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; As&#237; la puntuaci&#243;n de la escala componente f&#237;sico del cuestionario SF-36 alcanz&#243; una moderada relaci&#243;n inversamente proporcional con R5&#44; R20&#44; X5 y AX y una d&#233;bil relaci&#243;n directamente proporcional con la FVC&#44; FEV<span class="elsevierStyleInf">1</span> y FEF<span class="elsevierStyleInf">25-75&#37;</span>&#44; as&#237; como con diversas medidas de atenuaci&#243;n del par&#233;nquima &#40;MLD y P15&#41; en inspiraci&#243;n&#46; A su vez&#44; la puntuaci&#243;n obtenida en el term&#243;metro del EQ-5D se relacion&#243; de forma inversamente proporcional con R5 y X5 &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; Finalmente&#44; los modelos de regresi&#243;n lineal m&#250;ltiple solo retuvieron a la R5 y X5 como predictores independientes del componente f&#237;sico del cuestionario SF-36 y del term&#243;metro EQ-5D&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0035">fig&#46; 4</a> y <a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">Los principales resultados de nuestro estudio consisten en la demostraci&#243;n que la DPV resulta frecuente en fumadores sin LFA&#44; afectando a m&#225;s de un tercio de los mismos&#46; Aunque la presencia de esta alteraci&#243;n no tiene repercusi&#243;n sobre la espirometr&#237;a ni sobre los cambios en la atenuaci&#243;n del par&#233;nquima pulmonar&#44; se asocia a un deterioro incipiente de la CVRS&#44; hasta el punto de identificar una relaci&#243;n independiente entre la misma y algunos par&#225;metros de oscilaci&#243;n forzada&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">La frecuencia de DPV detectada en nuestros fumadores es superior a la identificada en estudios previos&#44; que refer&#237;an que un 5-13&#37; de fumadores con espirometr&#237;a normal pod&#237;an tener una IOS alterada<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22&#44;23</span></a>&#46; Sin embargo&#44; en dichos estudios no se establec&#237;a un punto de corte concreto para la detecci&#243;n de DPV y se mezclaban fumadores activos con exfumadores de distinto tiempo de evoluci&#243;n&#46; En contraste&#44; empleando puntos de corte predeterminados para R5-R20&#44; se ha referido la presencia de DPV en un 33-42&#37; de sujetos con asma y una espirometr&#237;a normal<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24&#44;25</span></a>&#46; Aunque la informaci&#243;n disponible en fumadores sin LFA resulta escasa&#44; Jetmalani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> encontraron que hasta un 51&#37; de dichos sujetos ten&#237;an al menos una anomal&#237;a en&#44; predominantemente en la resistencia respiratoria&#44; mientras que Berger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> describen que un 56&#37; de fumadores asintom&#225;ticos con espirometr&#237;a normal tienen una R5 elevada&#46; En cualquier caso&#44; el porcentaje de DPV identificada en fumadores sin LFA resulta concordante con la hallada mediante lavado m&#250;ltiple de nitr&#243;geno&#44; que permite identificar afectaci&#243;n de las v&#237;as a&#233;reas de conducci&#243;n en un 24&#37; de los sujetos y de las v&#237;as accinares en un 38&#37;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Un an&#225;lisis previo de una submuestra del estudio ECLIPSE puso de manifiesto la potencial utilidad de la IOS en las fases preliminares del da&#241;o pulmonar inducido por el tabaco<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; Aunque en dicho estudio no se detectaron diferencias en los valores absolutos de los par&#225;metros oscilom&#233;tricos entre pacientes con EPOC&#44; fumadores sin LFA y no fumadores&#44; probablemente por las notables diferencias en las caracter&#237;sticas antropom&#233;tricas y de tabaquismo entre los grupos&#44; el estudio demostr&#243; que la variabilidad intraindividual a corto y medio plazo de la impedancia del sistema respiratorio es muy discreta y aceptable cl&#237;nicamente<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; Pero lo m&#225;s interesante&#44; fue la identificaci&#243;n de un grupo de fumadores &#171;aparentemente sanos&#187; que ten&#237;an una AX elevada&#44; lo que llev&#243; a los autores a plantear la existencia de una alteraci&#243;n de las peque&#241;as v&#237;as a&#233;reas&#44; que constituir&#237;a una evidencia precoz de LFA no detectada con los par&#225;metros espirom&#233;tricos convencionales<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; En la misma l&#237;nea&#44; Frantz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> compararon a pacientes con una espirometr&#237;a normal y un diagn&#243;stico autorreferido de bronquitis cr&#243;nica o enfisema con sujetos sin dicho diagn&#243;stico&#44; comprobando que los primeros ten&#237;an valores m&#225;s elevados de R5&#44; R5-R20&#44; X5 y AX&#44; adem&#225;s de una mayor utilizaci&#243;n de medicaci&#243;n respiratoria&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Es interesante destacar que en nuestros fumadores sin evidencia de LFA no se hall&#243; relaci&#243;n alguna entre los par&#225;metros oscilom&#233;tricos y las medidas de atenuaci&#243;n del par&#233;nquima pulmonar en inspiraci&#243;n o espiraci&#243;n&#44; al igual que se ha descrito en el estudio ECLIPSE con respecto a las medidas de TC realizadas en inspiraci&#243;n<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; Para justificar esta discrepancia&#44; se ha propuesto la existencia de 3 tipos de afectaci&#243;n pulmonar evidenciada por TC&#58; engrosamiento de la pared de las v&#237;as a&#233;reas&#44; aumento de la atenuaci&#243;n pulmonar &#40;enfisema&#41; y mixto<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a>&#46; Las alteraciones de R5&#44; R5-R20&#44; <span class="elsevierStyleItalic">f</span>res y X5 se corresponder&#237;an sobre todo a la afectaci&#243;n de las v&#237;as a&#233;reas y a la mixta&#44; por lo que no es previsible su relaci&#243;n con los cambios de atenuaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a>&#46; Otra explicaci&#243;n complementaria podr&#237;a radicar en que la IOS y la TC son sensibles a cambios de la mec&#225;nica pulmonar producidos en distintas etapas de progresi&#243;n del da&#241;o de las v&#237;as a&#233;reas&#46; La resistencia se ve afectada por m&#250;ltiples factores&#44; entre los que destaca el calibre de las v&#237;as a&#233;reas&#44; particularmente cuando su estrechamiento es heterog&#233;neo&#44; generalizado e involucra a v&#237;as a&#233;reas centrales y perif&#233;ricas<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a>&#46; La reactancia tambi&#233;n es sensible al estrechamiento heterog&#233;neo y generalizado de la luz bronquial y bronquiolar&#44; pero adem&#225;s depende del cierre de las v&#237;as a&#233;reas<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a>&#44; por lo que tambi&#233;n podr&#237;a verse comprometida en caso de atrapamiento a&#233;reo&#46; Sin embargo&#44; se ha descrito que el atrapamiento a&#233;reo de los fumadores sin LFA es mucho menor al de los asm&#225;ticos<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a>&#44; por lo que probablemente esta alteraci&#243;n es muy discreta para inducir cambios relevantes en la atenuaci&#243;n pulmonar y generar un incremento adicional de la X5&#46; En definitiva&#44; se podr&#237;a plantear que la TC permite evaluar la afectaci&#243;n distal de par&#233;nquima&#44; mientras que la impedancia respiratoria&#44; y particularmente las resistencias respiratorias&#44; reflejan el calibre de las peque&#241;as v&#237;as a&#233;reas&#44; incluso mejor que el grosor de la pared bronquial&#44; puesto que esta &#250;ltima medida se realiza sobre generaciones bronquiales anteriores<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En nuestra opini&#243;n&#44; el resultado m&#225;s novedoso del presente estudio es el deterioro de la CVRS en fumadores activos con DPV que todav&#237;a no han desarrollado LFA&#46; Previamente&#44; se hab&#237;a descrito que los sujetos con una R5 elevada refieren sibilancias con mayor frecuencia<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a>&#46; La disminuci&#243;n de la CVRS en los fumadores con DPV&#44; situ&#225;ndose en una posici&#243;n intermedia entre los no fumadores o fumadores sin DPV y los fumadores con LFA&#44; podr&#237;a justificar las diferencias en la percepci&#243;n subjetiva de salud de los fumadores&#46; Resulta conocido que los fumadores tienen peor CVRS que los no fumadores<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> y que la persistencia del tabaquismo se asocia a un deterioro progresivo de la misma<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a>&#44; mientras que su abandono origina una mejor&#237;a de la calidad de vida<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&#46; Al igual que en nuestro estudio&#44; la afectaci&#243;n de la CVRS se puede detectar mediante cambios en las tarifas del cuestionario EQ-5D y en todos los dominios de los cuestionarios SF-12 y SF-36<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">33-35</span></a>&#44; aunque con un grado de afectaci&#243;n ligeramente superior al de nuestros pacientes&#44; probablemente por tratarse de sujetos de mayor edad&#44; con un mayor predominio de hombres&#44; sin una tasa acumulada de tabaquismo conocida y procedentes de otras &#225;reas geogr&#225;ficas&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Sin embargo&#44; lo m&#225;s destacado de la afectaci&#243;n de la CVRS en fumadores con espirometr&#237;a normal es la heterogeneidad de su intensidad&#44; que hasta el momento no ha podido ser adecuadamente justificada solo por una mayor intensidad del h&#225;bito<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> o una mayor dependencia de la nicotina<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a>&#46; La identificaci&#243;n que los fumadores con DPV son los que realmente experimentan un deterioro de su calidad de vida permite identificar un potencial riesgo de esta alteraci&#243;n funcional y es concordante con informaci&#243;n procedente de pacientes con EPOC&#44; en los que la DPV evaluada mediante IOS se relaciona con su estado de salud y con su nivel de disnea<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Resulta razonable asumir que la presencia de DPV en fumadores sin LFA es debida al estr&#233;s oxidativo y al da&#241;o directo originado por la inflamaci&#243;n local en las v&#237;as a&#233;reas perif&#233;ricas<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a>&#46; De hecho&#44; en fumadores con espirometr&#237;a normal&#44; se ha comprobado que aquellos que tienen DPV presentan un mayor recuento de linfocitos y neutr&#243;filos en su lavado broncoalveolar y mayores niveles de las citocinas IL-8 y eotaxina&#44; as&#237; como de la quimioquina CD3CL1<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a>&#44; que resulta particularmente importante por estar implicada en la diferenciaci&#243;n de c&#233;lulas Th17<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> y&#44; por lo tanto&#44; en la progresi&#243;n de las enfermedades respiratorias cr&#243;nicas&#46; A su vez&#44; la existencia de una relaci&#243;n directamente proporcional entre la R5 y los niveles en lavado broncoalveolar de IL-8&#44; eotaxina&#44; CD3CL1&#44; IL-12p70 y TGFalfa soporta su asociaci&#243;n con el grado de inflamaci&#243;n de las v&#237;as a&#233;reas distales<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">La informaci&#243;n disponible sobre el significado pron&#243;stico de la DPV en fumadores sin LFA todav&#237;a es incipiente&#44; aunque en fumadores y exfumadores sin EPOC del estudio COPDGene se ha comprobado que la alteraci&#243;n de las peque&#241;as v&#237;as a&#233;reas se relaciona con la tasa de deterioro anual del FEV<span class="elsevierStyleInf">1</span>&#44; que llega a equipararse con la de los pacientes con EPOC moderada&#44; aunque podr&#237;a resultar reversible si se controla la inflamaci&#243;n de las v&#237;as a&#233;reas m&#225;s distales<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&#46; Estos resultados parecen concordantes con los obtenidos en un peque&#241;o grupo de pacientes con EPOC moderada seguidos durante 5 a&#241;os&#44; en los que la X5&#44; AX y <span class="elsevierStyleItalic">f</span>res tambi&#233;n se relacionaron con la tasa de deterioro anual del FEV<span class="elsevierStyleInf">1</span><a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Nuestro estudio presenta diversas limitaciones&#46; Se trata de un estudio unic&#233;ntrico y con un limitado tama&#241;o muestral&#44; aunque suficiente para detectar diferencias en la CVRS entre los distintos grupos de sujetos&#46; Ello hace dif&#237;cil la extrapolaci&#243;n de los resultados a la poblaci&#243;n de fumadores en general&#46; A diferencia de otros an&#225;lisis&#44; hemos incluido un elevado n&#250;mero de mujeres y de sujetos en la edad media de la vida para disponer de una muestra m&#225;s representativa de la poblaci&#243;n fumadora actual&#44; aunque esto hace que la comparaci&#243;n con otros estudios deba ser cautelosa&#46; La evaluaci&#243;n de la atenuaci&#243;n del par&#233;nquima pulmonar se realiz&#243; mediante un software de uso cl&#237;nico&#44; que no proporciona medidas del grosor del calibre de las v&#237;as a&#233;reas&#46; A su vez&#44; tampoco se dispone de mediciones de la capacidad de difusi&#243;n pulmonar&#44; aunque la posibilidad de hallar alteraciones en este par&#225;metro entre los fumadores con o sin DPV parece poco probable por no mostrar diferencias en sus densidades de atenuaci&#243;n&#46; Por &#250;ltimo&#44; se trata de un estudio transversal&#44; por lo que del mismo no se pueden establecer inferencias pron&#243;sticas ni demostrar asociaci&#243;n o causalidad&#46; En esta misma l&#237;nea&#44; nuestros resultados no permiten establecer una recomendaci&#243;n sobre el manejo o tratamiento de los fumadores activos con DPV&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; la DPV en fumadores activos que todav&#237;a no han desarrollado LFA ni alteraciones en la densidad de atenuaci&#243;n pulmonar tiene impacto en la percepci&#243;n sintom&#225;tica de la salud&#44; puesto que los fumadores con DPV presentan un deterioro de su CVRS&#44; situ&#225;ndose en una posici&#243;n intermedia entre los no fumadores o fumadores sin DPV y los fumadores que han desarrollado una EPOC&#46; La utilizaci&#243;n de la oscilaci&#243;n forzada constituye un procedimiento simple&#44; r&#225;pido&#44; inocuo y de escaso coste que permite identificar DPV en m&#225;s de un tercio de fumadores activos&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financiaci&#243;n</span><p id="par0150" class="elsevierStylePara elsevierViewall">Proyecto de investigaci&#243;n parcialmente financiado por Chiesi&#46; Dicho patrocinador no ha participado en el dise&#241;o del estudio&#44; la recolecci&#243;n&#44; el an&#225;lisis y la interpretaci&#243;n de los datos&#44; la redacci&#243;n del manuscrito o la decisi&#243;n de enviar el art&#237;culo para su publicaci&#243;n&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0155" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introducci&#243;n</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La disfunci&#243;n de las peque&#241;as v&#237;as a&#233;reas &#40;DPV&#41; inducida por el tabaco contribuye precozmente a la patogenia de la limitaci&#243;n al flujo a&#233;reo &#40;LFA&#41;&#44; aunque resulta poco conocida su repercusi&#243;n en la percepci&#243;n de salud&#46; Se pretende evaluar la frecuencia de DPV en fumadores activos sin LFA y comparar la calidad de vida relacionada con la salud &#40;CVRS&#41; de no fumadores&#44; fumadores sin DPV&#44; fumadores con DPV y fumadores con LFA&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">En 53 fumadores activos sin LFA&#44; 20 fumadores con LFA y 20 no fumadores&#44; se utilizaron los cuestionarios SF-36 y EuroQoL y se realiz&#243; oscilometr&#237;a de impulsos&#44; espirometr&#237;a y determinaci&#243;n de las densidades de atenuaci&#243;n del par&#233;nquima pulmonar en inspiraci&#243;n y espiraci&#243;n m&#225;ximas&#46; Se consider&#243; que exist&#237;a DPV cuando la resistencia a 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5&#41;&#44; la diferencia R5-R20 y el &#225;rea de reactancia &#40;AX&#41; exced&#237;an su l&#237;mite superior de la normalidad&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El 35&#44;8&#37; de los fumadores sin LFA ten&#237;a DPV&#46; No se detectaron diferencias en los par&#225;metros espirom&#233;tricos ni la atenuaci&#243;n pulmonar entre los fumadores con o sin DPV y los no fumadores&#46; Sin embargo&#44; los fumadores con DPV presentaban una peor puntuaci&#243;n en los cuestionarios de CVRS que los fumadores sin DPV o los no fumadores&#44; e intermedia a los fumadores con LFA&#46; R5 y X5 fueron identificados como determinantes independientes de la CVRS en los fumadores sin LFA&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La DPV es frecuente en fumadores sin LFA&#44; afectando a un tercio de los mismos&#44; y condicionando de forma independiente su percepci&#243;n de salud&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Small airway dysfunction &#40;SAD&#41; caused by smoking contributes to the early onset of airflow limitation &#40;AFL&#41;&#44; although its impact on patients&#8217; perception of health is largely unknown&#46; We aimed to evaluate the frequency of SAD in active smokers without AFL&#44; and to compare health-related quality of life &#40;HRQoL&#41; of non-smokers&#44; smokers without SAD&#44; smokers with SAD&#44; and smokers with AFL&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A total of 53 active smokers without AFL&#44; 20 smokers with AFL&#44; and 20 non-smokers completed the SF-36 and EuroQoL questionnaires and performed impulse oscillometry and spirometry&#46; Pulmonary parenchymal attenuation was determined in inspiration and expiration&#46; SAD was determined to exist when resistance at 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5&#41;&#44; the difference between R5 and R20&#44; and reactance area &#40;AX&#41; exceeded the upper limit of normal&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">In total&#44; 35&#46;8&#37; of smokers without AFL had SAD&#46; No differences were detected in spirometric parameters or pulmonary attenuation between smokers with or without AFL and non-smokers&#46; However&#44; smokers with SAD had worse scores on HRQoL questionnaires than smokers without SAD or non-smokers&#44; and scores compared to smokers with AFL were intermediate&#46; R5 and X5 were identified as independent determinants of HRQoL in smokers without AFL&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SAD is common in smokers without AFL&#44; affecting one third of this population&#44; and independently affecting their perception of health&#46;</p></span>"
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            "apendice" => "<p id="par0165" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia></p>"
            "etiqueta" => "Anexo A"
            "titulo" => "Material suplementario"
            "identificador" => "sec0060"
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Distribuci&#243;n de los sujetos del estudio&#46;AX&#58; &#237;ndice de &#225;rea de reactancia de baja frecuencia&#59; DPV&#58; disfunci&#243;n peque&#241;as v&#237;as a&#233;reas&#59; FEV<span class="elsevierStyleInf">1</span>&#58; volumen espiratorios forzado en el primer segundo&#59; FVC&#58; capacidad vital forzada&#59; LFA&#58; limitaci&#243;n al flujo a&#233;reo&#59; LIN&#58; l&#237;mite inferior de la normalidad&#59; LSN&#58; l&#237;mite superior de la normalidad&#59; R5&#58; resistencia respiratoria a 5<span class="elsevierStyleHsp" style=""></span>Hz&#59; R20&#58; resistencia respiratoria a 20<span class="elsevierStyleHsp" style=""></span>Hz&#46;</p>"
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      1 => array:7 [
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        "etiqueta" => "Figura 2"
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        "mostrarDisplay" => false
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          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Comparaci&#243;n de las puntuaciones globales del componente f&#237;sico del cuestionario SF-36 y del term&#243;metro del cuestionario EQ-5D en los 4 grupos del estudio&#46; Las barras de error corresponden al error est&#225;ndar de la media&#46;DPV&#58; disfunci&#243;n peque&#241;as v&#237;as a&#233;reas&#59; EQ-5D&#58; <span class="elsevierStyleItalic">European Quality of Life-5 Dimensions</span>&#59; LFA&#58; limitaci&#243;n al flujo a&#233;reo&#59; SF-36&#58; <span class="elsevierStyleItalic">Short Form 36 Health Survey</span>&#46;</p>"
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        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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            "Alto" => 1872
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          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Comparaci&#243;n de las puntuaciones de los distintos dominios del cuestionario SF-36 entre los grupos de estudio&#46; Las barras de error corresponden al error est&#225;ndar de la media&#46;DPV&#58; disfunci&#243;n peque&#241;as v&#237;as a&#233;reas&#59; LFA&#58; limitaci&#243;n al flujo a&#233;reo&#59; SF-36&#58; <span class="elsevierStyleItalic">Short Form 36 Health Survey</span>&#46;</p>"
        ]
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      3 => array:7 [
        "identificador" => "fig0035"
        "etiqueta" => "Figura 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 2357
            "Ancho" => 1598
            "Tamanyo" => 94930
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        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Relaci&#243;n entre los par&#225;metros oscilom&#233;tricos y la calidad de vida relacionada con la salud en fumadores sin limitaci&#243;n al flujo a&#233;reo&#46; El panel superior &#40;A&#41; muestra la relaci&#243;n entre la resistencia respiratoria a 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5&#41; y el componente f&#237;sico del cuestionario <span class="elsevierStyleItalic">Short Form 36 Health Survey</span> &#40;SF-36&#41;&#44; mientras que el panel inferior &#40;B&#41; presenta la relaci&#243;n entre la reactancia capacitativa a 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;X5&#41; y el term&#243;metro del cuestionario <span class="elsevierStyleItalic">European Quality of Life-5 Dimensions</span> &#40;EQ-5D&#41;&#46;</p>"
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        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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            "identificador" => "at1"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">DPV&#58; disfunci&#243;n peque&#241;as v&#237;as a&#233;reas&#59; IMC&#58; &#237;ndice de masa corporal&#59; LFA&#58; limitaci&#243;n al flujo a&#233;reo&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">163<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">164<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;932&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEF<span class="elsevierStyleInf">25-75&#37;</span>&#44; &#37; pred&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No fumadores &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fumadores sin DPV &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fumadores con DPV &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fumadores con LFA &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MLD insp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;831<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;826<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;839<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;856<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30<a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0075"><span class="elsevierStyleSup">e</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0085"><span class="elsevierStyleSup">g</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LAV insp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;3<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subrango 1 &#40;&#8722;1&#46;000 a &#8722;951 UH&#41; insp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;6<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P15 insp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;907<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;902<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;914<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;939<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28<a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0075"><span class="elsevierStyleSup">e</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0090"><span class="elsevierStyleSup">h</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MLD esp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;692<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;685<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;703<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;805<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>50<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LAV esp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;1<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subrango 1 &#40;&#8722;1&#46;000 a &#8722;951 UH&#41; esp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P15 esp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;817<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;821<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;827<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;910<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48<a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;132<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>43&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;136<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;5<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0120"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;3<a class="elsevierStyleCrossRef" href="#tblfn0105"><span class="elsevierStyleSup">c</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0120"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Funci&#243;n f&#237;sica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;5<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0125"><span class="elsevierStyleSup">g</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rol f&#237;sico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dolor corporal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#44;1<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0115"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Salud general&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0105"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#44;1<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0125"><span class="elsevierStyleSup">g</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vitalidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;8<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0120"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;9<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0130"><span class="elsevierStyleSup">h</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Funcionamiento social&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0120"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;6<a class="elsevierStyleCrossRef" href="#tblfn0100"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rol emocional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Salud mental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;2<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;3<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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La disfunción de las pequeñas vías aéreas deteriora la calidad de vida de fumadores sin limitación al flujo aéreo
Small Airway Dysfunction Impairs Quality of Life Among Smokers With No Airflow Limitation
Cristina García-Queroa, José Carrerasa, Elisabet Martínez-Ceróna,b, Raquel Casitasa,b, Raúl Galeraa,b, Cristina Utrillac, Isabel Torresc, Francisco García-Ríoa,b,d,
Corresponding author
fgr01m@gmail.com

Autor para correspondencia.
a Servicio de Neumología, Hospital Universitario La Paz-Carlos III, IdiPAZ, Madrid, España
b Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, España
c Servicio de Radiodiagnóstico, Hospital Universitario La Paz, Madrid, España
d Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, España
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Dada su potencial relevancia patog&#233;nica&#44; resulta atractivo considerar que la presencia de DPV podr&#237;a constituir un paso previo al desarrollo de LFA<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> y mostrar incipientes repercusiones sobre la calidad de vida&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Por tanto&#44; establecemos como hip&#243;tesis que los fumadores sin LFA tienen una peor calidad de vida cuando han desarrollado DPV&#46; Nuestro objetivo principal ha sido comparar la calidad de vida de fumadores sin LFA pero con evidencia de DPV mediante IOS con la de no fumadores&#44; fumadores sin DPV y fumadores con LFA compatible con EPOC&#46; Como objetivos secundarios hemos pretendido determinar la frecuencia de DPV en fumadores sin LFA y comparar las densidades de atenuaci&#243;n del par&#233;nquima pulmonar entre los 4 grupos de sujetos&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sujetos del estudio</span><p id="par0025" class="elsevierStylePara elsevierViewall">En las consultas de deshabituaci&#243;n tab&#225;quica de nuestro centro&#44; se seleccionaron de forma consecutiva 53 fumadores activos sin evidencia de LFA y 20 fumadores activos con LFA compatible con EPOC&#46; En ambos casos&#44; los sujetos deb&#237;an tener de 40 a 70 a&#241;os y un consumo de tabaco acumulado medio de al menos 20 paquetes<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>a&#241;o&#46; Como grupo control&#44; se seleccionaron 20 sujetos de 40 a 70 a&#241;os del grupo de referencia de nuestro laboratorio&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica de Investigaci&#243;n del Hospital Universitario La Paz &#40;PI-1261&#41; y todos los participantes firmaron su consentimiento informado&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">En el <a class="elsevierStyleCrossRef" href="#sec0060">material suplementario</a> se proporciona informaci&#243;n m&#225;s detallada de los criterios de selecci&#243;n y de los procedimientos realizados&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Determinaciones</span><p id="par0035" class="elsevierStylePara elsevierViewall">La CVRS fue evaluada mediante la autoadministraci&#243;n de la versi&#243;n espa&#241;ola de los cuestionarios gen&#233;ricos <span class="elsevierStyleItalic">Short Form 36 Health Survey</span> &#40;SF-36&#41; y <span class="elsevierStyleItalic">European Quality of Life-5 Dimensions</span> &#40;EQ-5D&#41;&#44; y en los fumadores se utilizaron los test de Fagerstr&#246;m y Glover-Nilsson&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Se realiz&#243; una TC de t&#243;rax de alta resoluci&#243;n volum&#233;trica&#44; en inspiraci&#243;n y espiraci&#243;n m&#225;ximas&#44; mediante un equipo de 16 detectores &#40;Somatom Emotion 16&#44; Siemens Medical Solutions&#44; Erlangen&#44; Alemania&#41;&#46; Mediante un programa de an&#225;lisis semiautom&#225;tico &#40;Software syngo InSpace4D&#44; Siemens&#41;&#44; se determin&#243;&#44; tanto en inspiraci&#243;n como en espiraci&#243;n m&#225;ximas&#44; la densidad pulmonar media &#40;MLD&#41;&#44; el porcentaje de v&#243;xeles con valores de atenuaci&#243;n por debajo de &#8722;950 unidades Hounsfield &#40;UH&#41; &#40;LAV&#41; o entre &#8722;1&#46;000 y &#8722;951 UH &#40;subrango 1&#41; y los umbrales de atenuaci&#243;n correspondientes al percentil 15 &#40;P15&#41;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Todas las pruebas de funci&#243;n respiratoria fueron llevadas a cabo por una &#250;nica investigadora &#40;CGQ&#41; con un equipo MasterScreen &#40;Viasys Healthcare&#44; W&#252;rzburg&#44; Alemania&#41;&#46; La IOS se realiz&#243; seg&#250;n las recomendaciones vigentes<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a>&#46; Se solicit&#243; a los participantes que&#44; con una pinza nasal y sentados con la cabeza en una posici&#243;n neutral&#44; respiraran a volumen corriente con los labios sellados alrededor de una boquilla mientras apretaban firmemente sus mejillas con las manos&#46; Al menos&#44; se realizaron 3 registros aceptables &#40;valores de coherencia a 5 y 20<span class="elsevierStyleHsp" style=""></span>Hz<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#44;7 y 0&#44;9&#44; respectivamente&#41; con una duraci&#243;n de 30 segundos&#44; utilizando para el an&#225;lisis el promedio de 3 pruebas aceptables y repetibles &#40;variabilidad &#60;<span class="elsevierStyleHsp" style=""></span>10&#37;&#41;&#46; Como &#237;ndices de resistencia total y proximal de las v&#237;as a&#233;reas&#44; se utilizaron las resistencias respiratorias a 5 y 20<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5 y R20&#41;&#44; mientras que la ca&#237;da en la resistencia de 5 a 20<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5-R20&#41; fue considerada un indicador de la resistencia de las v&#237;as a&#233;reas perif&#233;ricas&#46; Adem&#225;s&#44; se determin&#243; la reactancia a 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;X5&#41; y el &#237;ndice de &#225;rea de reactancia de baja frecuencia &#40;AX&#41; como indicadores de la funci&#243;n de las v&#237;as respiratorias perif&#233;ricas&#46; Los datos obtenidos fueron interpretados en funci&#243;n de los valores de referencia europeos de Oostveen<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a>&#46; Inmediatamente despu&#233;s&#44; se realiz&#243; una espirometr&#237;a pre- y posbroncodilatador&#44; seg&#250;n la normativa vigente<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a>&#44; utilizando los valores de referencia <span class="elsevierStyleItalic">GLI</span><a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clasificaci&#243;n de los pacientes</span><p id="par0050" class="elsevierStylePara elsevierViewall">Se defini&#243; LFA compatible con EPOC un FEV<span class="elsevierStyleInf">1</span>&#47;FVC posbroncodilatador menor del l&#237;mite inferior de la normalidad<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a>&#46; La DPV fue definida por la presencia de una R5&#44; R5-R20 y AX mayores de su l&#237;mite superior de la normalidad<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a>&#46; En ausencia de LFA y DPV&#44; los sujetos fueron considerados control&#46; Seg&#250;n estos criterios&#44; los sujetos del estudio fueron clasificados en 4 grupos mutuamente excluyentes&#58; no fumadores control&#44; fumadores sin DPV&#44; fumadores con DPV y fumadores con LFA &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Por &#250;ltimo&#44; los pacientes con LFA fueron clasificados por gravedad&#44; grupo de riesgo y fenotipo de EPOC&#44; seg&#250;n las recomendaciones vigentes<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0055" class="elsevierStylePara elsevierViewall">La estimaci&#243;n del tama&#241;o muestral se realiz&#243; en funci&#243;n de una puntuaci&#243;n del componente f&#237;sico del cuestionario SF-36 de 49&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;7 obtenida en un estudio piloto en fumadores sin LFA &#40;datos no publicados&#41;&#46; Para detectar una diferencia de al menos 5 unidades&#44; mediante contraste bilateral&#44; con un riesgo alfa de 0&#44;05 y un riesgo beta de 0&#44;10&#44; se necesitar&#237;an 20 sujetos por cada grupo&#46; Seg&#250;n un estudio previo que refiri&#243; una prevalencia de DPV del 26&#44;3&#37; entre fumadores o exfumadores con cardiopat&#237;a isqu&#233;mica&#44; alcanzando el 38&#37; en fumadores activos<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a>&#44; para obtener 2 subgrupos de fumadores sin LFA comparables seg&#250;n la existencia o no de DPV&#44; se necesitar&#237;an 53 sujetos&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Los datos se presentan como n&#250;mero &#40;porcentaje&#41; o media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desviaci&#243;n est&#225;ndar&#44; seg&#250;n sus caracter&#237;sticas y una vez comprobado su ajuste a la distribuci&#243;n normal&#44; mediante la prueba de Shapiro-Wilk&#46; Para las comparaciones entre grupos se utiliz&#243; la prueba de chi-cuadrado y el an&#225;lisis de varianza con comparaciones m&#250;ltiples post-hoc mediante la prueba de Bonferroni&#46; La relaci&#243;n entre variables fue evaluada utilizando el an&#225;lisis de correlaci&#243;n de Pearson&#46; Aquellas variables que alcanzaron una relaci&#243;n significativa fueron introducidas en un an&#225;lisis de regresi&#243;n lineal m&#250;ltiple&#44; que utiliz&#243; el m&#233;todo de pasos escalonados hacia delante&#46; Un valor de p menor de 0&#44;05 fue considerado significativo y todos los an&#225;lisis fueron realizados con el programa SPSS 15&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; EE&#46;<span class="elsevierStyleHsp" style=""></span>UU&#46;&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><p id="par0065" class="elsevierStylePara elsevierViewall">Seg&#250;n los criterios establecidos&#44; fueron reclutados 20 sujetos no fumadores&#44; 53 fumadores activos sin LFA y 20 fumadores activos con LFA compatible con EPOC &#40;<a class="elsevierStyleCrossRef" href="#sec0060">tabla S1 del material suplementario</a>&#41;&#46; Los tres grupos resultaron homog&#233;neos en sexo&#44; edad&#44; talla&#44; peso e &#237;ndice de masa corporal &#40;<a class="elsevierStyleCrossRef" href="#sec0060">tabla S2 del material suplementario</a>&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">En el grupo de fumadores sin LFA&#44; se evidenci&#243; DPV en 19 sujetos&#44; lo que supone una frecuencia del 35&#44;8&#37; &#40;IC95&#37;&#58; 22&#44;9-48&#44;81&#37;&#41;&#46; En ning&#250;n sujeto del grupo de no fumadores se evidenci&#243; DPV&#44; por lo que todos fueron considerados como sujetos control&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#44; se muestran las caracter&#237;sticas antropom&#233;tricas y de consumo de tabaco de los 4 grupos finalmente constituidos&#46; Los par&#225;metros antropom&#233;tricos resultaron similares y no se apreciaron diferencias en las caracter&#237;sticas del consumo de tabaco&#44; dependencia de la nicotina ni dependencia psicol&#243;gica&#44; social o gestual entre los fumadores&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Al margen de las l&#243;gicas diferencias en las variables de la oscilaci&#243;n forzada utilizadas para definir los grupos&#44; los &#250;nicos par&#225;metros espirom&#233;tricos que resultaron menores en los fumadores con DPV que en los fumadores sin DPV fueron el FEF<span class="elsevierStyleInf">25&#37;</span> y el FEF<span class="elsevierStyleInf">25-75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">La afectaci&#243;n morfol&#243;gica del par&#233;nquima pulmonar evidenci&#243; una menor densidad de atenuaci&#243;n en los fumadores con LFA con respecto a los otros 3 grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46; Tanto en inspiraci&#243;n como en espiraci&#243;n&#44; los pacientes con EPOC mostraban una menor densidad pulmonar media&#44; mayores porcentajes de volumen de baja atenuaci&#243;n y vol&#250;menes de atenuaci&#243;n de entre &#8722;1&#46;000 a &#8722;951<span class="elsevierStyleHsp" style=""></span>UH y de entre &#8722;950 a &#8722;901<span class="elsevierStyleHsp" style=""></span>UH&#44; as&#237; como un menor P15&#46; Sin embargo&#44; no se detectaron diferencias en las densidades de atenuaci&#243;n entre fumadores con o sin DPV&#46; A su vez&#44; tampoco se evidenci&#243; relaci&#243;n alguna entre las medidas de atenuaci&#243;n del par&#233;nquima pulmonar y las variables de oscilaci&#243;n forzada en los 2 grupos de fumadores sin LFA&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> muestra la comparaci&#243;n de la CVRS entre los 4 grupos del estudio&#46; Adem&#225;s de las previsibles diferencias entre fumadores con LFA y los otros grupos&#44; resulta interesante destacar que los fumadores con DPV tienen una peor puntuaci&#243;n en las escalas componente f&#237;sico y componente mental del cuestionario SF-36 y en el term&#243;metro del cuestionario EQ-5D&#44; tanto con respecto a los controles no fumadores como a los fumadores sin DPV&#44; lo que evidencia una situaci&#243;n intermedia de deterioro de la calidad de vida entre estos sujetos y los fumadores con EPOC &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 2</a>&#41;&#46; El an&#225;lisis de los distintos dominios del cuestionario SF-36 muestra un comportamiento similar&#44; que afecta principalmente a los dominios relacionados con el componente f&#237;sico &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> y <a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">En los fumadores sin LFA&#44; tanto con DPV como sin ella&#44; no se hall&#243; relaci&#243;n alguna entre la CVRS y las caracter&#237;sticas antropom&#233;tricas&#44; edad de inicio&#44; intensidad del consumo de tabaco&#44; a&#241;os de tabaquismo ni con las puntuaciones de los test de Fagerstr&#246;m o Glover-Nilsson&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la calidad de vida de estos sujetos se relacion&#243; con diversos par&#225;metros funcionales y morfol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; As&#237; la puntuaci&#243;n de la escala componente f&#237;sico del cuestionario SF-36 alcanz&#243; una moderada relaci&#243;n inversamente proporcional con R5&#44; R20&#44; X5 y AX y una d&#233;bil relaci&#243;n directamente proporcional con la FVC&#44; FEV<span class="elsevierStyleInf">1</span> y FEF<span class="elsevierStyleInf">25-75&#37;</span>&#44; as&#237; como con diversas medidas de atenuaci&#243;n del par&#233;nquima &#40;MLD y P15&#41; en inspiraci&#243;n&#46; A su vez&#44; la puntuaci&#243;n obtenida en el term&#243;metro del EQ-5D se relacion&#243; de forma inversamente proporcional con R5 y X5 &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; Finalmente&#44; los modelos de regresi&#243;n lineal m&#250;ltiple solo retuvieron a la R5 y X5 como predictores independientes del componente f&#237;sico del cuestionario SF-36 y del term&#243;metro EQ-5D&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0035">fig&#46; 4</a> y <a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">Los principales resultados de nuestro estudio consisten en la demostraci&#243;n que la DPV resulta frecuente en fumadores sin LFA&#44; afectando a m&#225;s de un tercio de los mismos&#46; Aunque la presencia de esta alteraci&#243;n no tiene repercusi&#243;n sobre la espirometr&#237;a ni sobre los cambios en la atenuaci&#243;n del par&#233;nquima pulmonar&#44; se asocia a un deterioro incipiente de la CVRS&#44; hasta el punto de identificar una relaci&#243;n independiente entre la misma y algunos par&#225;metros de oscilaci&#243;n forzada&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">La frecuencia de DPV detectada en nuestros fumadores es superior a la identificada en estudios previos&#44; que refer&#237;an que un 5-13&#37; de fumadores con espirometr&#237;a normal pod&#237;an tener una IOS alterada<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22&#44;23</span></a>&#46; Sin embargo&#44; en dichos estudios no se establec&#237;a un punto de corte concreto para la detecci&#243;n de DPV y se mezclaban fumadores activos con exfumadores de distinto tiempo de evoluci&#243;n&#46; En contraste&#44; empleando puntos de corte predeterminados para R5-R20&#44; se ha referido la presencia de DPV en un 33-42&#37; de sujetos con asma y una espirometr&#237;a normal<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24&#44;25</span></a>&#46; Aunque la informaci&#243;n disponible en fumadores sin LFA resulta escasa&#44; Jetmalani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> encontraron que hasta un 51&#37; de dichos sujetos ten&#237;an al menos una anomal&#237;a en&#44; predominantemente en la resistencia respiratoria&#44; mientras que Berger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> describen que un 56&#37; de fumadores asintom&#225;ticos con espirometr&#237;a normal tienen una R5 elevada&#46; En cualquier caso&#44; el porcentaje de DPV identificada en fumadores sin LFA resulta concordante con la hallada mediante lavado m&#250;ltiple de nitr&#243;geno&#44; que permite identificar afectaci&#243;n de las v&#237;as a&#233;reas de conducci&#243;n en un 24&#37; de los sujetos y de las v&#237;as accinares en un 38&#37;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Un an&#225;lisis previo de una submuestra del estudio ECLIPSE puso de manifiesto la potencial utilidad de la IOS en las fases preliminares del da&#241;o pulmonar inducido por el tabaco<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; Aunque en dicho estudio no se detectaron diferencias en los valores absolutos de los par&#225;metros oscilom&#233;tricos entre pacientes con EPOC&#44; fumadores sin LFA y no fumadores&#44; probablemente por las notables diferencias en las caracter&#237;sticas antropom&#233;tricas y de tabaquismo entre los grupos&#44; el estudio demostr&#243; que la variabilidad intraindividual a corto y medio plazo de la impedancia del sistema respiratorio es muy discreta y aceptable cl&#237;nicamente<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; Pero lo m&#225;s interesante&#44; fue la identificaci&#243;n de un grupo de fumadores &#171;aparentemente sanos&#187; que ten&#237;an una AX elevada&#44; lo que llev&#243; a los autores a plantear la existencia de una alteraci&#243;n de las peque&#241;as v&#237;as a&#233;reas&#44; que constituir&#237;a una evidencia precoz de LFA no detectada con los par&#225;metros espirom&#233;tricos convencionales<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; En la misma l&#237;nea&#44; Frantz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> compararon a pacientes con una espirometr&#237;a normal y un diagn&#243;stico autorreferido de bronquitis cr&#243;nica o enfisema con sujetos sin dicho diagn&#243;stico&#44; comprobando que los primeros ten&#237;an valores m&#225;s elevados de R5&#44; R5-R20&#44; X5 y AX&#44; adem&#225;s de una mayor utilizaci&#243;n de medicaci&#243;n respiratoria&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Es interesante destacar que en nuestros fumadores sin evidencia de LFA no se hall&#243; relaci&#243;n alguna entre los par&#225;metros oscilom&#233;tricos y las medidas de atenuaci&#243;n del par&#233;nquima pulmonar en inspiraci&#243;n o espiraci&#243;n&#44; al igual que se ha descrito en el estudio ECLIPSE con respecto a las medidas de TC realizadas en inspiraci&#243;n<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a>&#46; Para justificar esta discrepancia&#44; se ha propuesto la existencia de 3 tipos de afectaci&#243;n pulmonar evidenciada por TC&#58; engrosamiento de la pared de las v&#237;as a&#233;reas&#44; aumento de la atenuaci&#243;n pulmonar &#40;enfisema&#41; y mixto<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a>&#46; Las alteraciones de R5&#44; R5-R20&#44; <span class="elsevierStyleItalic">f</span>res y X5 se corresponder&#237;an sobre todo a la afectaci&#243;n de las v&#237;as a&#233;reas y a la mixta&#44; por lo que no es previsible su relaci&#243;n con los cambios de atenuaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a>&#46; Otra explicaci&#243;n complementaria podr&#237;a radicar en que la IOS y la TC son sensibles a cambios de la mec&#225;nica pulmonar producidos en distintas etapas de progresi&#243;n del da&#241;o de las v&#237;as a&#233;reas&#46; La resistencia se ve afectada por m&#250;ltiples factores&#44; entre los que destaca el calibre de las v&#237;as a&#233;reas&#44; particularmente cuando su estrechamiento es heterog&#233;neo&#44; generalizado e involucra a v&#237;as a&#233;reas centrales y perif&#233;ricas<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a>&#46; La reactancia tambi&#233;n es sensible al estrechamiento heterog&#233;neo y generalizado de la luz bronquial y bronquiolar&#44; pero adem&#225;s depende del cierre de las v&#237;as a&#233;reas<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a>&#44; por lo que tambi&#233;n podr&#237;a verse comprometida en caso de atrapamiento a&#233;reo&#46; Sin embargo&#44; se ha descrito que el atrapamiento a&#233;reo de los fumadores sin LFA es mucho menor al de los asm&#225;ticos<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a>&#44; por lo que probablemente esta alteraci&#243;n es muy discreta para inducir cambios relevantes en la atenuaci&#243;n pulmonar y generar un incremento adicional de la X5&#46; En definitiva&#44; se podr&#237;a plantear que la TC permite evaluar la afectaci&#243;n distal de par&#233;nquima&#44; mientras que la impedancia respiratoria&#44; y particularmente las resistencias respiratorias&#44; reflejan el calibre de las peque&#241;as v&#237;as a&#233;reas&#44; incluso mejor que el grosor de la pared bronquial&#44; puesto que esta &#250;ltima medida se realiza sobre generaciones bronquiales anteriores<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En nuestra opini&#243;n&#44; el resultado m&#225;s novedoso del presente estudio es el deterioro de la CVRS en fumadores activos con DPV que todav&#237;a no han desarrollado LFA&#46; Previamente&#44; se hab&#237;a descrito que los sujetos con una R5 elevada refieren sibilancias con mayor frecuencia<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a>&#46; La disminuci&#243;n de la CVRS en los fumadores con DPV&#44; situ&#225;ndose en una posici&#243;n intermedia entre los no fumadores o fumadores sin DPV y los fumadores con LFA&#44; podr&#237;a justificar las diferencias en la percepci&#243;n subjetiva de salud de los fumadores&#46; Resulta conocido que los fumadores tienen peor CVRS que los no fumadores<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> y que la persistencia del tabaquismo se asocia a un deterioro progresivo de la misma<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a>&#44; mientras que su abandono origina una mejor&#237;a de la calidad de vida<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&#46; Al igual que en nuestro estudio&#44; la afectaci&#243;n de la CVRS se puede detectar mediante cambios en las tarifas del cuestionario EQ-5D y en todos los dominios de los cuestionarios SF-12 y SF-36<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">33-35</span></a>&#44; aunque con un grado de afectaci&#243;n ligeramente superior al de nuestros pacientes&#44; probablemente por tratarse de sujetos de mayor edad&#44; con un mayor predominio de hombres&#44; sin una tasa acumulada de tabaquismo conocida y procedentes de otras &#225;reas geogr&#225;ficas&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Sin embargo&#44; lo m&#225;s destacado de la afectaci&#243;n de la CVRS en fumadores con espirometr&#237;a normal es la heterogeneidad de su intensidad&#44; que hasta el momento no ha podido ser adecuadamente justificada solo por una mayor intensidad del h&#225;bito<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> o una mayor dependencia de la nicotina<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a>&#46; La identificaci&#243;n que los fumadores con DPV son los que realmente experimentan un deterioro de su calidad de vida permite identificar un potencial riesgo de esta alteraci&#243;n funcional y es concordante con informaci&#243;n procedente de pacientes con EPOC&#44; en los que la DPV evaluada mediante IOS se relaciona con su estado de salud y con su nivel de disnea<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Resulta razonable asumir que la presencia de DPV en fumadores sin LFA es debida al estr&#233;s oxidativo y al da&#241;o directo originado por la inflamaci&#243;n local en las v&#237;as a&#233;reas perif&#233;ricas<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a>&#46; De hecho&#44; en fumadores con espirometr&#237;a normal&#44; se ha comprobado que aquellos que tienen DPV presentan un mayor recuento de linfocitos y neutr&#243;filos en su lavado broncoalveolar y mayores niveles de las citocinas IL-8 y eotaxina&#44; as&#237; como de la quimioquina CD3CL1<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a>&#44; que resulta particularmente importante por estar implicada en la diferenciaci&#243;n de c&#233;lulas Th17<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> y&#44; por lo tanto&#44; en la progresi&#243;n de las enfermedades respiratorias cr&#243;nicas&#46; A su vez&#44; la existencia de una relaci&#243;n directamente proporcional entre la R5 y los niveles en lavado broncoalveolar de IL-8&#44; eotaxina&#44; CD3CL1&#44; IL-12p70 y TGFalfa soporta su asociaci&#243;n con el grado de inflamaci&#243;n de las v&#237;as a&#233;reas distales<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">La informaci&#243;n disponible sobre el significado pron&#243;stico de la DPV en fumadores sin LFA todav&#237;a es incipiente&#44; aunque en fumadores y exfumadores sin EPOC del estudio COPDGene se ha comprobado que la alteraci&#243;n de las peque&#241;as v&#237;as a&#233;reas se relaciona con la tasa de deterioro anual del FEV<span class="elsevierStyleInf">1</span>&#44; que llega a equipararse con la de los pacientes con EPOC moderada&#44; aunque podr&#237;a resultar reversible si se controla la inflamaci&#243;n de las v&#237;as a&#233;reas m&#225;s distales<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&#46; Estos resultados parecen concordantes con los obtenidos en un peque&#241;o grupo de pacientes con EPOC moderada seguidos durante 5 a&#241;os&#44; en los que la X5&#44; AX y <span class="elsevierStyleItalic">f</span>res tambi&#233;n se relacionaron con la tasa de deterioro anual del FEV<span class="elsevierStyleInf">1</span><a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Nuestro estudio presenta diversas limitaciones&#46; Se trata de un estudio unic&#233;ntrico y con un limitado tama&#241;o muestral&#44; aunque suficiente para detectar diferencias en la CVRS entre los distintos grupos de sujetos&#46; Ello hace dif&#237;cil la extrapolaci&#243;n de los resultados a la poblaci&#243;n de fumadores en general&#46; A diferencia de otros an&#225;lisis&#44; hemos incluido un elevado n&#250;mero de mujeres y de sujetos en la edad media de la vida para disponer de una muestra m&#225;s representativa de la poblaci&#243;n fumadora actual&#44; aunque esto hace que la comparaci&#243;n con otros estudios deba ser cautelosa&#46; La evaluaci&#243;n de la atenuaci&#243;n del par&#233;nquima pulmonar se realiz&#243; mediante un software de uso cl&#237;nico&#44; que no proporciona medidas del grosor del calibre de las v&#237;as a&#233;reas&#46; A su vez&#44; tampoco se dispone de mediciones de la capacidad de difusi&#243;n pulmonar&#44; aunque la posibilidad de hallar alteraciones en este par&#225;metro entre los fumadores con o sin DPV parece poco probable por no mostrar diferencias en sus densidades de atenuaci&#243;n&#46; Por &#250;ltimo&#44; se trata de un estudio transversal&#44; por lo que del mismo no se pueden establecer inferencias pron&#243;sticas ni demostrar asociaci&#243;n o causalidad&#46; En esta misma l&#237;nea&#44; nuestros resultados no permiten establecer una recomendaci&#243;n sobre el manejo o tratamiento de los fumadores activos con DPV&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; la DPV en fumadores activos que todav&#237;a no han desarrollado LFA ni alteraciones en la densidad de atenuaci&#243;n pulmonar tiene impacto en la percepci&#243;n sintom&#225;tica de la salud&#44; puesto que los fumadores con DPV presentan un deterioro de su CVRS&#44; situ&#225;ndose en una posici&#243;n intermedia entre los no fumadores o fumadores sin DPV y los fumadores que han desarrollado una EPOC&#46; La utilizaci&#243;n de la oscilaci&#243;n forzada constituye un procedimiento simple&#44; r&#225;pido&#44; inocuo y de escaso coste que permite identificar DPV en m&#225;s de un tercio de fumadores activos&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financiaci&#243;n</span><p id="par0150" class="elsevierStylePara elsevierViewall">Proyecto de investigaci&#243;n parcialmente financiado por Chiesi&#46; Dicho patrocinador no ha participado en el dise&#241;o del estudio&#44; la recolecci&#243;n&#44; el an&#225;lisis y la interpretaci&#243;n de los datos&#44; la redacci&#243;n del manuscrito o la decisi&#243;n de enviar el art&#237;culo para su publicaci&#243;n&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0155" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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              "titulo" => "Clasificaci&#243;n de los pacientes"
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    "fechaRecibido" => "2018-12-10"
    "fechaAceptado" => "2019-01-11"
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          "palabras" => array:5 [
            0 => "Tabaco"
            1 => "Peque&#241;as v&#237;as a&#233;reas"
            2 => "Oscilaci&#243;n forzada"
            3 => "Calidad de vida"
            4 => "Limitaci&#243;n al flujo a&#233;reo"
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          "palabras" => array:5 [
            0 => "Smoking"
            1 => "Small airways"
            2 => "Forced oscillation"
            3 => "Quality of life"
            4 => "Airflow limitation"
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    "resumen" => array:2 [
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introducci&#243;n</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La disfunci&#243;n de las peque&#241;as v&#237;as a&#233;reas &#40;DPV&#41; inducida por el tabaco contribuye precozmente a la patogenia de la limitaci&#243;n al flujo a&#233;reo &#40;LFA&#41;&#44; aunque resulta poco conocida su repercusi&#243;n en la percepci&#243;n de salud&#46; Se pretende evaluar la frecuencia de DPV en fumadores activos sin LFA y comparar la calidad de vida relacionada con la salud &#40;CVRS&#41; de no fumadores&#44; fumadores sin DPV&#44; fumadores con DPV y fumadores con LFA&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">En 53 fumadores activos sin LFA&#44; 20 fumadores con LFA y 20 no fumadores&#44; se utilizaron los cuestionarios SF-36 y EuroQoL y se realiz&#243; oscilometr&#237;a de impulsos&#44; espirometr&#237;a y determinaci&#243;n de las densidades de atenuaci&#243;n del par&#233;nquima pulmonar en inspiraci&#243;n y espiraci&#243;n m&#225;ximas&#46; Se consider&#243; que exist&#237;a DPV cuando la resistencia a 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5&#41;&#44; la diferencia R5-R20 y el &#225;rea de reactancia &#40;AX&#41; exced&#237;an su l&#237;mite superior de la normalidad&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El 35&#44;8&#37; de los fumadores sin LFA ten&#237;a DPV&#46; No se detectaron diferencias en los par&#225;metros espirom&#233;tricos ni la atenuaci&#243;n pulmonar entre los fumadores con o sin DPV y los no fumadores&#46; Sin embargo&#44; los fumadores con DPV presentaban una peor puntuaci&#243;n en los cuestionarios de CVRS que los fumadores sin DPV o los no fumadores&#44; e intermedia a los fumadores con LFA&#46; R5 y X5 fueron identificados como determinantes independientes de la CVRS en los fumadores sin LFA&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La DPV es frecuente en fumadores sin LFA&#44; afectando a un tercio de los mismos&#44; y condicionando de forma independiente su percepci&#243;n de salud&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Small airway dysfunction &#40;SAD&#41; caused by smoking contributes to the early onset of airflow limitation &#40;AFL&#41;&#44; although its impact on patients&#8217; perception of health is largely unknown&#46; We aimed to evaluate the frequency of SAD in active smokers without AFL&#44; and to compare health-related quality of life &#40;HRQoL&#41; of non-smokers&#44; smokers without SAD&#44; smokers with SAD&#44; and smokers with AFL&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A total of 53 active smokers without AFL&#44; 20 smokers with AFL&#44; and 20 non-smokers completed the SF-36 and EuroQoL questionnaires and performed impulse oscillometry and spirometry&#46; Pulmonary parenchymal attenuation was determined in inspiration and expiration&#46; SAD was determined to exist when resistance at 5<span class="elsevierStyleHsp" style=""></span>Hz &#40;R5&#41;&#44; the difference between R5 and R20&#44; and reactance area &#40;AX&#41; exceeded the upper limit of normal&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">In total&#44; 35&#46;8&#37; of smokers without AFL had SAD&#46; No differences were detected in spirometric parameters or pulmonary attenuation between smokers with or without AFL and non-smokers&#46; However&#44; smokers with SAD had worse scores on HRQoL questionnaires than smokers without SAD or non-smokers&#44; and scores compared to smokers with AFL were intermediate&#46; R5 and X5 were identified as independent determinants of HRQoL in smokers without AFL&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SAD is common in smokers without AFL&#44; affecting one third of this population&#44; and independently affecting their perception of health&#46;</p></span>"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Distribuci&#243;n de los sujetos del estudio&#46;AX&#58; &#237;ndice de &#225;rea de reactancia de baja frecuencia&#59; DPV&#58; disfunci&#243;n peque&#241;as v&#237;as a&#233;reas&#59; FEV<span class="elsevierStyleInf">1</span>&#58; volumen espiratorios forzado en el primer segundo&#59; FVC&#58; capacidad vital forzada&#59; LFA&#58; limitaci&#243;n al flujo a&#233;reo&#59; LIN&#58; l&#237;mite inferior de la normalidad&#59; LSN&#58; l&#237;mite superior de la normalidad&#59; R5&#58; resistencia respiratoria a 5<span class="elsevierStyleHsp" style=""></span>Hz&#59; R20&#58; resistencia respiratoria a 20<span class="elsevierStyleHsp" style=""></span>Hz&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LAV insp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;3<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subrango 1 &#40;&#8722;1&#46;000 a &#8722;951 UH&#41; insp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;6<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P15 insp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;907<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;902<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;914<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;939<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28<a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0075"><span class="elsevierStyleSup">e</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0090"><span class="elsevierStyleSup">h</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MLD esp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;692<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;685<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;703<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;805<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>50<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LAV esp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;1<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subrango 1 &#40;&#8722;1&#46;000 a &#8722;951 UH&#41; esp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P15 esp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;817<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;821<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;827<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;910<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48<a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MLD insp-esp&#44; UH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;132<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;141<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;136<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>40<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0070"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0080"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LAV insp-esp&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dolor corporal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#44;1<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0115"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Salud general&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0105"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#44;1<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;0<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0125"><span class="elsevierStyleSup">g</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vitalidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;8<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0120"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;9<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0110"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0130"><span class="elsevierStyleSup">h</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Funcionamiento social&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0120"><span class="elsevierStyleSup">f</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;6<a class="elsevierStyleCrossRef" href="#tblfn0100"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rol emocional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Salud mental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;2<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;7<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;3<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">EQ-5D</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tarifa EVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;000<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;905<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;145&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;817<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;158<a class="elsevierStyleCrossRef" href="#tblfn0095"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;864<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;143<a class="elsevierStyleCrossRef" href="#tblfn0100"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tarifa ET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;000<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;937<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;871<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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Article information
ISSN: 03002896
Original language: Spanish
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