UNIVERSITAT DE BARCELONA Facultat de Medicina Departament de Cirurgía i Especialitats Mèdico-Quirúrgiques TESIS DOCTORAL ASOCIACIÓN DE BRONQUIECTASIAS PULMONARES Y PATOLOGÍA NASOSINUSAL. ESTUDIO DE LOS ASPECTOS EPIDEMIOLÓGICOS, ETIOLÓGICOS, DE DIAGNÓSTICO Y TRATAMIENTO. José Mª Guilemany Toste
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UNIVERSITAT DE BARCELONA Facultat de Medicina
Departament de Cirurgía i Especialitats Mèdico-Quirúrgiques
TESIS DOCTORAL
ASOCIACIÓN DE BRONQUIECTASIAS PULMONARES Y PATOLOGÍA
NASOSINUSAL. ESTUDIO DE LOS ASPECTOS EPIDEMIOLÓGICOS,
ETIOLÓGICOS, DE DIAGNÓSTICO Y TRATAMIENTO.
José Mª Guilemany Toste
UNIVERSITAT DE BARCELONA Facultat de Medicina
Departament de Cirurgía i Especialitats Mèdico-Quirúrgiques
Tesis presentada por el Licenciado José Mª Guilemany Toste a fin de optar al título de Doctor por la Universidad de Barcelona, realizado en la Unitat de Rinologia i Clínica de l’Olfacte, Servei d’Oto-rino-laringologia, Hospital Clínic i Universitari de Barcelona. Directores de tesis Tutor de tesis Joaquim Mullol i Miret Manuel Bernal-Sprekelsen Cèsar Picado i Vallés
Alteración mucociliar Fibrosis quística Discinesia ciliar primaria Síndrome de Young
Neumonitis inflamatoria
Aspiración, reflujo gastroesofágico Inhalación de tóxicos (drogas, gases)
Anormalidad árbol traqueobronquial
Traqueobroncomegalia (síndrome de Mounier-Kuhn) Defectos del cartílago (síndrome de Williams-Campbell) Secuestro pulmonar Traqueobroncomalacia Bronquio traqueal
Asociada a otras enfermedades
Enfermedades sistémicas: artritis reumatoide, lupus, síndrome de Sjögren, síndrome de Marfan, policondritis recidivante, espondilitis anquilosante, sarcoidosis Enfermedad inflamatorio intestinal: colitis ulcerosa, enfermedad de Crohn Otras enfermedades respiratorias: asma, EPOC, síndroma de Swyer-James Déficit de alfa1-antitripsina, síndrome de la uñas amarillas
Aspergilosis o ABPA Panbronquiolitis difusa No conocida
I. Parte Teórica Tesis Doctoral
88
variable, deficiencias de la formación de anticuerpos). Algunas
bronquiectasias parecen haberse desarrollado a raíz de una bronquiolitis
infecciosa en la infancia (sarampión, virus respiratorio sincitial). También
pueden presentarse asociadas a enfermedades sistémicas (artritis
reumatoide, síndrome de Sjögren) o a enfermedades inflamatorias
intestinales (colitis ulcerosa, enfermedad de Crohn). En un número
reducido de casos pueden ser consecuencia de la aspiración de sustancias
tóxicas que lesionan los bronquios.
Entre las enfermedades que ocasionan bronquiectasias y patología
nasosinusal debemos destacar:
3.1 Fibrosis quística (FQ). Es la alteración genética de tipo
autosómico recesivo más común en la población de tipo caucásico. Uno de
cada 25 individuos es portador del gen.241,242 Se calcula que afecta
aproximadamente a 1 de cada 3.000-10.000 nacidos vivos por año. El gen
responsable de la FQ se encuentra en el locus simple del brazo largo del
cromosoma 7. La deleción de tres pares de bases o mutación Delta F508
acontece aproximadamente en el 70% de todos los cromosomas de la FQ.
La proteína defectuosa, codificada por este gen anormal, tiene una
estructura similar a una clase de proteínas conocida por ser activa en el
transporte epitelial y ha sido denominada Cystic Fibrosis Transmembrane
Regulator (CFTR).243 Esta proteína defectuosa contribuye a un mal
funcionamiento de las canales del cloro que provoca un aumento de la
viscosidad del moco dificultando su eliminación y favoreciendo la
colonización por Stafilococus aureus y Pseudomona mucoide.
Otras mutaciones han sido identificadas cerca del locus afectado. Los
pacientes afectos de FQ se caracterizan por presentar infecciones repetidas
en el tracto respiratorio, insuficiencia pancreática exocrina e infertilidad. La
radiografía de tórax244 muestra afectación de los lóbulos superiores en
estados precoces, que se vuelven difusos con la progresión de la
Tesis Doctoral I. Parte Teórica
89
enfermedad. La función pulmonar puede ser normal o presentar un patrón
de tipo obstructivo o mixto. En la presentación adulta los síntomas han
estado usualmente presentes por años, pero muchas veces no son tomados
en cuenta al ser moderados. El adulto puede presentar bronquiectasias,
rinosinusitis, insuficiencia pancreática, pancreatitis aguda, colelitiasis e
infertilidad. La obstrucción nasal es el síntoma más frecuente entre los
pacientes con FQ. La incidencia de poliposis nasal es de más del 20% de
los pacientes. Encontramos diferentes patrones de rinosinusitis: pólipos
nasales, rinosinusitis crónica purulenta y mucopiosinusitis del antro del
seno maxilar con protusión de la pared nasal lateral.245 Esta última entidad
recibe el nombre de pseudomucocele maxilar. En el diagnóstico de la FQ es
importante el test del sudor246 (en la enfermedad las concentraciones de
sodio o cloro son de 60 mmol/l o superior, siendo en individuos normales y
portadores del gen FQ de hasta 30 mmol/l), el estudio genotípico y la TC
torácica y nasosinusal. Los objetivos del tratamiento de la FQ son: reducir
la obstrucción, controlar las infecciones, disminuir la inflamación y mejorar
el estado nutricional. A nivel nasal el tratamiento consiste en lavados
nasales con suero fisiológico, corticoterapia intranasal, antibioticoterapia y,
en caso necesario, la cirugía endoscópica nasosinusal (CENS).
3.2 Discinesia ciliar primaria (DCP). Es una enfermedad congénita
en la que existe una alteración total o parcial en la función de las células
ciliadas.247 La DCP es una enfermedad autosómica recesiva que afecta a
uno de cada 16.000 nacidos vivos, presentándose clínicamente con
rinosinusitis y bronquiectasias y, de forma menos frecuente, esterilidad en
los varones. En el síndrome de discinesia (dificultad para el movimiento)
ciliar primaria existen alteraciones estructurales o funcionales en los
microtúbulos de los cilios que son responsables del movimiento de los
mismos. Estas alteraciones originan un mal aclaramiento del moco de los
cilios, con las consiguientes infecciones bronquiales supurativas y
I. Parte Teórica Tesis Doctoral
90
bronquiectasias. Se alteran todas las estructuras donde existen cilios:
epitelios de las vías respiratorias, senos paranasales, trompa de Eustaquio, y
espermatozoides (astenospermia).248
Entre los individuos afectados, el 50% presenta el síndrome de
Kartagener caracterizado por la triada de bronquiectasias, rinosinusitis
crónica y situs inversus (dextrocardia).249 Una rinitis con presencia de
rinorrea anterior se encuentra en todos los pacientes afectos de DCP,
acompañados en algunos casos de pólipos nasales y disminución o pérdida
parcial o completa del olfato. En la TC de senos es típico encontrar
ocupación de los senos etmoidales y maxilares, junto a hipoplasia de seno
frontal. El diagnóstico se realiza mediante una combinación de pruebas
como son: tiempo de sacarina, ON nasal, biopsia nasal en la que se puede
observar la frecuencia de batida de los cilios y la densidad de los mismos
mediante microscopía electrónica.250 En el manejo del paciente con DCP
resulta de gran importancia la fisioterapia respiratoria con drenaje postural
y el uso de antibióticos en las agudizaciones por infecciones respiratorias.
La realización de una polipectomía endoscópica o una CENS es
beneficiosa en aquellos pacientes con una rinosinusitis crónica rebelde al
tratamiento.
El diagnóstico se establece por estudio ultraestructural de muestras
obtenidas de mucosa nasal, en las que se suele observar la ausencia de los
brazos de la dineína o disposición anómala de los microtúbulos. Estudios
recientes han demostrado unos niveles bajos de ON nasal en los pacientes
afectos,251 considerándose diagnóstico niveles de ON inferiores a 100 ppb.
3.3 Síndrome de Young. Consiste en la presencia de la triada:
bronquiectasias, rinosinusitis crónica e infertilidad. En estos pacientes la
actividad ciliar es normal siendo el moco muy viscoso. La biopsia nasal
estudiada bajo microscopía electrónica no muestra cambios en la estructura
de los cilios en estos pacientes.252 La azoespermia causante de la
Tesis Doctoral I. Parte Teórica
91
infertilidad es debida a la obstrucción del epidídimo, ya que la
espermiogénesis es totalmente normal. El diagnóstico se basa en la clínica
(enfermedad sinopulmonar crónica, azoespermia), así como en la exclusión
de fibrosis quística y de síndromes de inmovilidad ciliar.253
3.4 Deficiencia de alfa1-antitripsina (ATT). Esta es una
glicoproteína producida por los hepatocitos, cuya función es la de inhibir
las proteasas (elastasa), en particular las liberadas por los neutrófilos, en su
misión reparadora y de limpieza de agentes externos a nivel pulmonar. Al
inhabilitar las proteasas evita la destrucción de tejidos sanos en nuestro
organismo.254 El gen que la codifica está situado en el cromosoma 14. En el
pulmón el déficit de ATT produce enfisema por una destrucción progresiva
de los alveolos en la tercera y cuarta década de la vida. El humo del tabaco
contribuye a la destrucción pulmonar, dado que aumenta la actividad de la
elastasa, disminuye la actividad de la ATT por su oxidación e inactiva la
síntesis de elastina, interfiriendo en la reparación pulmonar; por lo que
dejar de fumar debe ser la principal prioridad del paciente diagnosticado
con déficit de ATT.255
El enfisema producido por el déficit de ATT es panacinar, donde
existe destrucción de todo el acini. Se localiza frecuentemente en las bases,
existiendo un aumento de la distensibilidad “compliance" pulmonar. La
disminución de los niveles de ATT produce un desequilibrio entre esta
proteína (antiproteasa) y la elastasa (proteasa). Al no existir suficiente
cantidad de ATT, las elastasas siguen destruyendo progresivamente la
elastina de las paredes alveolares.256 Se consideran como niveles normales
de la proteína ATT en sangre los comprendidos entre 150 a 350 mg/dl ó
20-53 µM. Niveles por debajo de los 80 mg/dl u 11 µM ponen en riesgo al
individuo de padecer alguna de las enfermedades relacionadas con su
déficit. A nivel pulmonar se observan enfisema, bronquitis crónica,
bronquiectasias, asma de difícil tratamiento y neumonías de repetición. Las
I. Parte Teórica Tesis Doctoral
92
recomendaciones para realizar mediciones cuantitativas de ATT son:
enfisema precoz, antecedentes familiares, disnea o tos en varios miembros
de una misma familia de las mismas o diferentes generaciones, adultos con
bronquiectasias sin etiología evidente, todos los pacientes con enfermedad
obstructiva pulmonar, enfermedad hepática de causa desconocida,
pacientes asmáticos que no responden a tratamiento o padecen paniculitis
inexplicable.257 La rinitis alérgica y las rinosinusitis de repetición también
constituyen una manifestación frecuente en estos pacientes, incluso en
ausencia de enfermedad obstructiva pulmonar.258
4. Histopatología. La bronquiectasia (BQ) es la destrucción y la
dilatación anormal, permanente e irreversible de uno o más bronquios
medianos y pequeños, producidas por la pérdida de los componentes
musculares y elásticos de la pared bronquial. En las bronquiectasias se
encuentran áreas de la pared bronquial destruidas e inflamadas
crónicamente constituyendo un círculo vicioso; las células ciliadas están
dañadas o destruidas y la producción de moco está aumentada, perdiéndose
el tono normal de la pared.259 El aumento de la producción de moco facilita
el crecimiento de las bacterias, obstruye los bronquios y favorece el
estancamiento de las secreciones infectadas, con un daño posterior de la
pared bronquial.260 La inflamación puede extenderse a los alvéolos y
producir bronconeumonía, formación de tejido cicatricial y pérdida del
tejido pulmonar sano. Además, la inflamación de los vasos sanguíneos de
la pared bronquial puede ocasionar expectoración hemoptóica o hemoptisis
franca. En el examen anatomopatológico se observan dilataciones
bronquiales, hipertrofia de la mucosa, en ocasiones con metaplasia
escamosa, infiltrado linfocítario de la pared bronquial y desaparición de
cartílago, músculo y fibras elásticas que son substituidas por tejido
cicatricial.261 El análisis del esputo y las biopsias de la mucosa bronquial
han mostrado un aumento de la concentración de la elastasa, IL-8, TNF-α y
Tesis Doctoral I. Parte Teórica
93
prostanoides.262,263 Los marcadores de inflamación sistémica también estan
elevados en los pacientes con BQ en fase estable.263
5. Aspectos clínicos y diagnóstico. El curso clínico de las BQ no
quísticas es muy variable. Algunos pacientes no tienen síntomas o son muy
leves, mientras que otros los presentan a diario con progresiva pérdida de
funcionalidad pulmonar y por consiguiente de calidad de vida. El síntoma
que caracteriza a esta enfermedad es la tos productiva crónica ó broncorrea
mucopurulenta y maloliente. Es típico que la tos sea intermitente durante el
día y que predomine por las mañanas al levantarse, debido a la retención de
las secreciones durante la noche y que, a su vez, aumente con las
infecciones agudas. En ocasiones no existe ningún síntoma evidente o una
simple tos seca. En un 50-70% de los casos hay esputo sanguinolento
(hemoptoico). Con frecuencia suelen haberse padecido neumonías de
repetición o crisis de disnea (dificultad para respirar) antes de ser
diagnosticados de esta enfermedad. No es rara la presencia de episodios
febriles, deterioro del estado general, adelgazamiento del paciente y, en
ocasiones, olor nauseabundo de las secreciones y, en consecuencia, del
paciente.
Actualmente, el manejo apropiado (fundamentalmente por el
correcto uso de los antibióticos) de las bronquiectasias ha conseguido
reducir o hacer desaparecer las complicaciones que tradicionalmente
presentaban éstos pacientes debidas a la extensión local o a distancia de la
infección (abscesos cerebrales, abscesos pulmonares). Por este motivo, las
complicaciones más frecuentes son: hemoptisis, obstrucción crónica al
flujo aéreo, acropaquia, insuficiencia respiratoria crónica y el cor
pulmonale.
El diagnóstico de las BQ es clínico-radiológico.264 En la auscultación
pulmonar pueden encontrarse crepitantes, roncus y/o sibilancias, todos
I. Parte Teórica Tesis Doctoral
94
ellos indicativos de abundante secreción bronquial. Inicialmente en las
bronquiectasias difusas puede haber un patrón obstructivo moderado-
severo y al avanzar la enfermedad aparecer un patrón restrictivo. Es
bastante frecuente la hiperreactividad bronquial. La placa de tórax y la TC
pulmonar convencional no son suficientemente sensibles en el diagnóstico
de BQ. Actualmente la confirmación de las mismas es por la TC de alta
resolución pulmonar, que ha desplazado a la broncografía con contraste. La
extensión de las BQ en la TC de alta resolución está correlacionada con
cambios funcionales y pronóstico del paciente. Otras pruebas
complementarias van encaminadas a demostrar la causa de las
bronquiectasias.
6. Microbiología. La complicación más frecuente de las BQs es la
sobreinfección.265 La colonización más frecuente en estos pacientes es por
cm2; Volumen: cm3) /pulmonar (espirometría: l) y NO nasal (ppb) y
exhalado (ppb).
Resultados: la mayoria de los pacientes (n=68; 77%) con bronquiectasias
en fase estable cumplieron criterios EP3OS para RSC, presentando como
síntomas nasales predominantes: rinorrea anterior (98,5%) y rinorrea
posterior (91%) y obstrucción nasal (90%). Además, la pérdida de olfato
fué uno de los síntomas más frecuentes (77,2%) en los pacientes con RSC
con pólipos. El tamaño de los pólipos fué de leve a moderado (1,6±0,1)
encontrándose en el 25% de los pacientes. Los pacientes con RSC
presentaron en la TC una mayor frecuencia de ocupación de los senos
III. Trabajo Experimental Tesis Doctoral
106
maxilares, etmoidales y complejo ostiomeatal (puntuación total: 8,4±0,4).
También se observó una mayor afectación en la rinomanometría entre los
pacientes con (590±37 cm3/s) y sin RSC (854±81,5 cm3/s), y en la
rinometría acústica entre los pacientes con RSC, con o sin pólipos nasales.
El óxido nítrico nasal está disminuido en los pacientes con RSC con
pólipos (347±62 ppb; p<0,001) comparado con los que no tienen pólipos
(683±76 ppb). Se observó una correlación inversa entre la puntuación del
complejo ostiomeatal y el NO nasal (R= -0,36; p<0,01). El óxido nítrico
exhalado está incrementado en los pacientes con poliposis nasal (11,1±2
ppb), pero sin significancia estadística. A nivel sistémico, la PCR está más
elevada en los paciente que cumplen criterios de rinosinusitis crónica. Los
pacientes con RSC (7,2±0,5; p<0,001) presentan un mayor índice de
extensión de BQs que los pacientes sin RSC (3,7±0,7). La prevalencia de
patología nasosinusal es similar entre los pacientes con bronquiectasias de
origen postinfeccioso e idiopático.
Conclusiones: Los pacientes con BQs presentaron una alta prevalencia de
rinosinusitis crónica (77%) y poliposis nasal (25%). La PCR está
significativamente elevada en los pacientes con RSC comparada con los
pacientes sin patología nasosinusal. Los pacientes con BQs, los senos
maxilares y los etmoidales, junto a obliteración del complejo ostiomeatal
fueron los más afectados entre los pacientes con RSC con o sin pólipos,
mientras que los pacientes con RSC sin PN tienen una puntuación total
inferior en la TC nasosinusal que los pacientes con RSC con PN.
La gravedad de las BQs se relaciona con la presencia de RSC o PN.
Los pacientes con RSC presentaron una mayor afectación pulmonar
evaluada mediante la TC pulmonar de alta resolución en comparación con
los pacientes sin RSC, sin existir diferencias entre pacientes con o sin PN.
Tesis Doctoral III. Trabajo Experimental
107
La prevalencia de RSC y de PN es alta en los pacientes con BQs,
independientemente de que la causa sea post-infecciosa o idiopática.
El ON nasal está disminuido en los pacientes con RSC con PN y su
valor disminuye conforme aumenta la afectación del complejo ostiomeatal.
Las concentraciones de ON nasal fueron similares en los diferentes grupos,
excepto en los pacientes con PN, en los cuales el NO nasal se encontró en
concentraciones menores que en los pacientes sin RSC y sin pólipos.
También se observó que el ON nasal estaba más bajo conforme aumentaba
la puntuación del complejo ostiomeatal en la TC nasosinusal.
Conclusión general: los pacientes con BQs deberían ser evaluados
siempre a fin de descartar una RSC con o sin pólipos, y a su vez los
pacientes con RSC con o sin pólipos deberían ser estudiados para
enfermedades de la vía aérea inferior, incluyendo BQs.
Tesis Doctoral III. Trabajo Experimental
109
Estudio 2: The impact of bronchiectasis associated to sinonasal disease
on quality of life. Respir Med 2006;100:1997-2003. DOI: 10.1016/j.rmed.2006.02.016
Introducción: los pacientes afectos de BQs se caracterizan por presentar
tos productica crónica lo cual supone un empeoramiento de su calidad de
vida. No se han realizado estudios sobre la afectación de la calidad de vida
en pacientes con BQs y patologia nasosinusal.
Objetivos: se estudió si los pacientes afectos de bronquiectasias con
patología a nivel nasal presentan una peor calidad de vida comparado con
la población general española utilizando un cuestionario genérico de
calidad de vida (SF-36).
Métodos: se incluyeron 60 pacientes con BQs y patología nasosinusal que
fueron evaluados por: síntomas nasales (obstrucción, rinorrea anterior,
rinorrea posterior, dolor facial, estornudos, picor nasal, pérdida de olfato;
RASP: 0-3), tamaño de los pólipos (Lildholdt: 0-3) y calidad de vidad (SF-
36: 0-100).
Resultados: La edad media de los pacientes con BQs fué de 52±16 años
(rango: 18-78 años). 39 pacientes (65%) fueron mujeres. Los pacientes con
BQs presentaban predominantemente rinorrea anterior (1,9±0,9) y posterior
(1,8±0,9), pérdida del olfato (0,9±1), obstrucción nasal (1,65±0,9) y
estornudos (1,2±1). Veinticinco pacientes (41,6%) con BQs presentaban
pólipos nasales en la endoscopia con un tamaño medio de Lildholdt:
1,5±0,4 (rango:1–2). Los pacientes con BQ y PN tenían puntuaciones
mayores (P<0,05) de obstrucción nasal (2,05±0,8) y pérdida del olfato
(1,4±1) que los pacientes con BQs sin pólipos (1,4±0,8; 0,5±0,8)
respectivamente. En comparación con la población general española, los
pacientes con BQs presentaban peor calidad de vida en todos los dominios
del SF-36 (Función física: 90,3±17,1 vs. 76±22; Rol físico: 87,6±30,4 vs.
III. Trabajo Experimental Tesis Doctoral
110
71±42; Dolor corporal: 81,9±26 vs. 62,3±24,9; Salud general: 70,9±19,6
vs. 35,5±18; Vitalidad: 71,6±21 vs. 48,7±17,3; Rol emocional: 94,6±21,8
vs. 71,3±42,5; Función social: 94,1±15,6 vs. 75,2±28,3; Salud mental:
77,7±18,7 vs. 65,4±21,4; Sumario físico: 82,7±23,3 vs. 46,5±26,7; Sumario
mental: 84,5±19,3 vs. 39,7±27,3). No existen diferencias significativas
entre la calidad de vida de los pacientes con BQs con o sin PN.
Las mujeres mostraron peor función física (diferencia: 13,1; P<0,05
y 95%IC: 1,7–24,5) y peor función social (diferencia: 15,7; P<0,05 y
95%IC: 0,4–31) que los hombres. Las mujeres con BQs tenían peores
puntuaciones de calidad de vida (P<0,05) que las mujeres de la población
general española en la función física, dolor corporal, salud general,
vitalidad, función social y el rol emocional. Los hombres también
mostraron peores puntuaciones de calidad de vida (P<0,05) que los
hombres de la población general española en el dolor corporal, salud
general y vitalidad. No existen diferencias significativas entre mujeres y
hombres en cuanto a la edad, función pulmonar, presencia de pólipos
nasales, síntomas nasales, tabaco y duración de la enfermedad.
Los pacientes mostraron una VEMS% de 81±3,4. No existía
correlación entre los 2 sumarios de calidad de vida y la función pulmonar:
SF (r: 0,21; P=0,242) y SM (r: 0,095; P=0,599).
Conclusiones: en comparación con la población general española, los
pacientes afectos de BQs presentaron peor puntuación (p<0,05) en todos
los dominios del SF-36. Los hombres presentaron puntuaciones más altas
en función física y social que las mujeres. La afectación en la calidad de
vida resultó ser independiente de la edad, función pulmonar, síntomas
nasales, tabaquismo y duración de la enfermedad. En el sexo masculino, los
pacientes con BQs presentaron peor calidad de vida que los de la población
general española en dolor corporal, salud general y vitalidad. En el sexo
femenino, las pacientes con BQs presentaron peor calidad de vida que las
Tesis Doctoral III. Trabajo Experimental
111
de la población general española, además de los dominios anteriores, en
función física, función social y rol emocional.
Conclusión general: estos resultados sugieren que las BQs con RSC
producen una importante impacto en la calidad de vida, sin que exista un
impacto adicional en los pacientes con RSC y pólipos nasales.
Tesis Doctoral III. Trabajo Experimental
113
Estudio 3. United airways: the impact of chronic rhinosinusitis and nasal
polyps in bronchiectasic patient’s quality of life. Allergy 2009;64:1524-9. DOI:10.1111/j.1398-9995.2009.02011.x
Introducción: resultados anteriores sugieren que las BQs con RSC
producen una importante impacto en la calidad de vida, sin que exista un
impacto añadido en los pacientes con RSC y pólipos nasales. No obstante,
no se han realizado estudios comparativos sobre calidad de vida en
pacientes con BQs con o sin patologia nasosinusal.
Objetivos: se evaluó el impacto de la CRS con o sin pólipos en la calidad
de vida de los pacientes con BQs, y a su vez si existía correlación en la
calidad de vida entre la vía aérea superior e inferior y a nivel general.
Métodos: se estudiaron prospectivamente 80 pacientes con BQs, de los
cuales 60 presentaban RSC según los criterios EP3OS. Los pacientes
realizaron cuestionarios de calidad de vida específicos de vía superior
(SNOT-20), de vía inferior (SGRQ) y genéricos (SF-36).
Resultados: los pacientes con RSC presentaron unos valores superiores del
SNOT-20 total (2,1±0,1; p<0,001) que los pacientes sin patología nasal
(0,4±0,06). Los pacientes con RSC presentaron también valores superiores
del SGRQ total (43,7±2,2; p<0,001) que los pacientes sin patología
nasosinusal (24,7±2,5). En el SF-36, los pacientes con RSC presentaron
una peor calidad de vida tanto en el sumario mental (65,5±4,7; p<0,05)
como en el físico (64±3,4; p<0,05) en comparación a los pacientes sin
patología nasosinusal (SM: 78,3±5,3; SF: 76,2±3,3; respectivamente). La
puntuación total del SNOT-20 se correlacionó tanto con la puntuación total
del SGRQ (r:0,72; p<0,01) como con el componente físico del SF-36 (r:-
0,63; p<0,01). La puntuación total del SGRQ se correlacionó con el
componente físico del SF-36 (r:-0,58; p<0,05) y con el VEMS (r:-
0,41;p<0,05).
III. Trabajo Experimental Tesis Doctoral
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Conclusiones: La RSC con o sin pólipos tiene un considerable impacto en
la calidad de vida de los pacientes con BQs. La puntuación global del
SNOT-20 en pacientes con BQ que presentaban criterios de RSC, con o sin
pólipos, fue de 2,1. A su vez, la puntuación en los pacientes con BQs sin
RSC fue de 0,4. Así pues, en nuestro estudio en la calidad de vida, no
existen diferencias medidas por SNOT-20 entre pacientes con RSC con o
sin pólipos.
Los pacientes con BQs mostraban una importante reducción de su
calidad de vida cuando presentaban RSC asociada, sin existir una
repercusión añadida por tener PN. En los pacientes afectados de EPOC con
síntomas nasales, no se ha observado ninguna correlación entre el SNOT-
20 y el SGRQ total, o alguno de sus dominios (impacto, actividades o
síntomas). Sin embargo, en los pacientes con BQ sí que hay correlación
entre el SNOT-20, el SGRQ y el SF-36, asociándose la intensidad de los
síntomas nasales con el empeoramiento de la calidad de vida tanto en el
SNOT-20 y el SGRQ como en el SF-36. Los pacientes con RSC con PN
presentaron una mayor pérdida de olfato que los pacientes con RSC sin PN,
pero sin provocar un empeoramiento de la calidad de vida de los pacientes
(SNOT-20, SGRQ, y SF-36).
Conclusión general: estos resultados sugieren que la RSC evaluada, tanto
mediante cuestionarios específicos como genéricos, tiene un considerable
impacto sobre la calidad de vida de los pacientes con BQs.
Tesis Doctoral III. Trabajo Experimental
115
Estudio 1. United airway again: high prevalence of rhinosinusitis and nasal
polyps in bronchiectasis. Allergy 2009;64:790-7. DOI: 10.111/j.1398-9995.2008.01892.x
Original article
United airways again: high prevalence of rhinosinusitis and nasal
polyps in bronchiectasis
Bronchiectasis (BQ) is a chronic bronchial disease with astructural derangement of the bronchial wall, withpermanent and irreversible destruction and dilatation,retained secretions and recurrent infections that causeinflammation, obstruction, damage of the lower airway,significant impact on health care and impairment of thequality of life (1, 2). BQ are a consequence of a variety ofdifferent diseases where infection and excessive mucousproduction appear to be the most important contributoryfactors. Although more than 50% of BQ cases are stillconsidered idiopathic, the study of contributing potentialcauses may have important implications for the manage-ment of the disease (3).Chronic rhinosinusitis (CRS) is an inflammatory dis-
ease of the nose and sinus mucosa that, despite differenthypotheses about its cause, remains poorly understood
(4). CRS has become one of the most common chronicdiseases (5), with studies reporting that in the generalpopulation up to 6% of subjects suffered from chronicnasal discharge (6). Nasal polyps (NP) are smooth, grape-like structures that arise from the inflamed nasal mucosa.NP usually occurs in association with CRS. Smelldisorders are more prevalent in patients with NP thanin CRS patients with no NP (7).
The recently coined concept �united airways�, alsoknown as �one airway, one disease�, maintains thatinflammatory processes of the upper and lower airwayoften co-exist and share common etiopathogenic mech-anisms. It has been mainly explored with reference toasthma and rhinitis. Epidemiological data indicate thatasthma and rhinitis frequently occur in the same patient.It has also been reported that the severity of rhinitis
Background: Although various relationships between the lower and upperairways have been found, the association of bronchiectasis with chronic rhin-osinusitis and nasal polyps has not been thoroughly evaluated. This study wasundertaken to examine the association of idiopathic and postinfective bronchi-ectasis with chronic rhinosinusitis and nasal polyposis.Methods: In a prospective study, 56 patients with idiopathic and 32 withpostinfective bronchiectasis were evaluated for chronic rhinosinusitis and nasalpolyposis by using EP3OS criteria and assessing: symptoms score, nasal endos-copy, sinonasal and chest CT scan, nasal and lung function and nasal andexhaled NO.Results: Most bronchiectasis patients (77%) satisfied the EP3OS criteria forchronic rhinosinusitis, with anterior (98.5%) and posterior (91%) rhinorrheaand nasal congestion (90%) being the major symptoms. Patients presentedmaxillary, ethmoidal and ostiomeatal complex occupancy with a total CT scoreof 8.4 ± 0.4 (0–24). Using endoscopy, nasal polyps with a moderate score of1.6 ± 0.1 (0–3) were found in 25% of patients. Nasal NO was significantlylower in patients with nasal polyposis (347 ± 62 ppb) than in those withoutthem (683 ± 76 ppb; P < 0.001), and inversely correlated (R = )0.36;P < 0.01) with the ostiomeatal complex occupancy. In the chest CT scan,patients with chronic rhinosinusitis showed a higher bronchiectasis severityscore (7.2 ± 0.5; P < 0.001) than patients without (3.7 ± 0.7). The prevalenceof chronic rhinosinusitis, nasal polyps and other outcomes were similar inidiopathic and postinfective bronchiectasis.Conclusions: The frequent association of chronic rhinosinusitis and nasalpolyposis with idiopathic and postinfective BQ supports the united airwaysconcept, and it suggests that the two type of bronchiectasis share commonetiopathogenic mechanisms.
J. M. Guilemany1,4, J. Angrill2,I. Alobid1,4, S. Centellas1,4,L. Pujols3,4, J. Bartra2,4,M. Bernal-Sprekelsen1,4, A. Valero2,4,C. Picado2,3,4, J. Mullol1,3,4
1Department of Otorhinolaryngology, Rhinology Unitand Smell Clinic; 2Department of Medicine,Pneumology and Respiratory Allergy, Hospital Cl�nic,University of Barcelona; 3Institut d�InvestigacionsBiom�diques August Pi i Sunyer (IDIBAPS); 4Centrode Investigaci�n Biom�dica en Red deEnfermedades Respiratorias (CIBERes), Barcelona,Catalonia, Spain
Joaquim MullolRhinology Unit & Smell ClinicDepartment of OtorhinolaryngologyHospital Cl�nic i Universitaric/ Villarroel 17008036 BarcelonaCataloniaSpain
directly correlates with asthma severity. NP are alsofrequently associated with asthma. Over 84% of sino-nasal CT scans have been found to be abnormal in severeasthmatic patients, with a correlation between the CTscores, sputum eosinophilia and pulmonary function (8).In addition, both the medical and surgical treatments ofCRS and NP may benefit concomitant asthma (9).Upper airway symptoms are also frequent in patients
with chronic obstructive pulmonary disease (COPD) andcause impairment in patients� quality of life (10).Increased nasal inflammation has also been reported inCOPD patients (11). Patients with allergic and nonaller-gic asthma and COPD show increased nasal symptomsand more nasal inflammation (12).CRS and NP frequently occur in cystic fibrosis and
primary ciliary dyskinesia. Both are distinguish diseaseswith clear pathological mechanisms and with a conse-quence of pulmonary pathology due to recurrent airwayinfections (13). However, few studies have addressed thepotential co-morbidity between noncystic BQ and upperairway disease, including CRS and NP. We hypothesizethat, according to the �united airway� concept, mostso-called idiopathic bronchiectasis should be the conse-quence of a process affecting the entire airways, includingthe nose and the paranasal sinuses. In contrast, BQconsidered secondary to infectious insults of the lowerairways (postinfective BQ) usually occurring in early years,such as after pneumonia or in whooping cough, should notbe necessarily associatedwithCRS. If this hypothesis holdstrue, most patients with idiopathic bronchiectasis shouldsuffer from nasal and sinus diseases, and the severity ofCRS and bronchiectasis should also be correlated. Incontrast, in postinfective BQ, the upper airway shouldrarely be involved. To test this hypothesis, we: (1) examinedthe association of idiopathic and postinfective BQ andCRS with and without NP and (2) assessed the prevalenceof symptoms, sinusal occupancy, nasal polyp size, nasaland lung function and inflammation in patients with BQand concomitant CRS and NP.
Methods
Study subjects
Eighty-eight consecutive patients with idiopathic and postinfectiveBQ, diagnosed in the pneumology clinic, were included in a pro-spective study from April 2004–June 2006. The diagnosis of BQ wasperformed on the basis of characteristic clinical symptoms and CTscanning. The Ethics Committee of our institution approved thestudy and signed informed consent was obtained from all patients.
Diagnosis and extent of BQ
BQ predisposing factors were assessed: serum immunoglobulin (Ig),IgG, IgA, IgM, IgG subclasses, specific antibody response topneumococal antigens, alpha1-antitrypsin deficiency, cystic fibrosis(sweat test and genotyping), allergic bronchopulmonary aspergil-losis and ciliary dysfunction. A high resolution CT (HRCT) scan of
the chest was performed during the 3-month period prior to thesinonasal examination and the extent of BQ in each lobe was gra-ded, using a scale from 0 to 3 (0, no involvement; 1, segmentinvolved; 2, more than one segment involved and 3, gross cystic BQinvolving the entire lobe) (14). Forced spirometry was performedaccording to standard methods and percent-predicted FEV1
(FEV1%), FVC and FEV1/FVC was chosen for analysis, as previ-ously reported. Exhaled nitric oxide (eNO) was measured accordingto standardized methods (15).Postinfective BQ was diagnosed when the patient reported a
history of symptoms appearing immediately after a severe infection,such as pneumonia, tuberculosis or whooping cough. Idiopathic BQwas diagnosed when known causes of BQ had been ruled-out.
Diagnosis and extent of sinusitis and nasal polyps
Patients with BQ were evaluated for CRS and NP following EP3OSguidelines (4). The diagnosis of NP was based on the visualizationof nasal polyps under endoscopic examination. To characterize theinvolvement of upper airway disease in patients with BQ, the fol-lowing diagnostic tools were used: nasal symptom score, nasalendoscopy, sinonasal CT-scan, nasal function and nasal NO.Nasal congestion/obstruction/blockage, reduction or loss of the
sense of smell, anterior rhinorrhea, postnasal drip, facial pain/pressure, itching and sneezing were scored using the Rasp classifi-cation (0–3) (16). Polyp size was scored from 0 to 3 for each nasalcavity using nasal endoscopy, following Lildholdt�s classification(17). A radiologist blindly staged sinus occupation for each patient,using CT scanning and the Lund-MacKay score system (0–24) (18).Nasal airflow was measured by active anterior rhinomanometry andexpressed as the flow generated at a pressure of 150 Pa (cm3/s).Nasal volume within the distance of 6 cm from the nostrils (volume0–6 cm3) was measured using acoustic rhinometry, according to amethod previously reported (15). nNO was obtained from onenostril using a negative pressure pump with a flow rate of 3 l/min, asreported elsewhere (15).
Other studies
Skin prick testing to most common allergens, nasal eosinophilia,blood eosinophil counts and serum total and specific IgE levels werecarried out, using previously reported standard methods.
Statistical analysis
Data analysis and statistics were performed using spss for Windows(SPSS 12.0, Chicago, IL, USA). Comparisons between categoricalvariables used the Pearson�s v2 statistic (or the Fisher�s exact test forsmall samples). When comparing continuous variables with cate-gorical predictors, the Student�s t-test was used. Pearson correlationcoefficients were used to examine the association between gender,age, nasal symptoms, nasal polyps, CT opacification, lung function,nasal patency and nasal/exhaled nitric oxide. Values of P < 0.05were considered statistically significant.
Results
Demographic data
Fifty-six of the 88 patients (64%) were classified as havinga postinfective disease, while 32 (36%) were classified ashaving an idiopathic disease, of those one had an
inflammatory bowel disease, and another rheumatoidarthritis. The mean age was 55 ± 2 years (ranging from21 years to 78 years), 6% were current smokers and 24%were ex-smokers. The mean age at BQ diagnosis was40 ± 2 years. Patients with NP (36.5 ± 5 years) werediagnosed with BQ earlier than patients with no sinonasalpathology (47 ± 4 years). Patients with CRS, 69% ofthem female, had a significantly higher female ratio(3 : 1), and this was even higher in patients with CRS-NP(5.6 : 1), compared to patients with no CRS (1 : 1)(Table 1).
Allergic and immunologic studies
C-reactive protein level was significantly increased inpatients with CRS (1.3 ± 0.2 mg/dl; P < 0.05) com-pared with patients with no CRS (0.6 ± 0.2 mg/dl). Themain allergic and immunologic characteristics aredescribed and compared with normal values in Table 2.No significant differences between groups (including CRSvs No CRS) were found.
Lung function
Mean FEV1 was 83 ± 3% predicted. FEV1 in patientswith CRS (81 ± 3%) was lower than in those with noCRS (90 ± 4%) but the difference did not reach statis-tical significance (P = 0.06). No other differences werefound in spirometry between groups, and no correlationwas observed with nasal symptoms, nasal polyposis orCT scores (Table 1).
Chest CT-scan
Patients with CRS (7.2 ± 0.5; P < 0.001) showed ahigher BQ severity score than patients with no CRS(3.7 ± 0.7) (Fig. 1). No differences were observedbetween patients with and without NP.
Sinonasal symptoms
Seventy-seven percent of patients fulfilled the EP3OScriteria for CRS. Anterior rhinorrhea (89%), postnasaldrip (77%) and nasal congestion (77%) were scored bypatients as major complaints, while sneezing (59%), facialpain (40%), reduction/loss of smell (39%) and itching(36%) were less frequent. Patients with CRS reportedanterior rhinorrhea (98.5%), postnasal drip (91%) andnasal congestion (90%), with significant differences(P < 0.001) in all symptoms except sneezing, comparedto patients with no CRS. Patients with CRS hadsignificant higher scores (P < 0.001) in total symptom
Table 1. Epidemiological characteristics of BQ patients included in the study
All BQ patients No CRS CRS CRS without NP CRS with NP ID PI
BQ, bronchiectasis; CRS, chronic rhinosinusitis; NP, nasal polyposis; ID, idiopathic BQ; PI, postinfectious BQ; SEM, standard error of the mean; M, male; F, female; FEV1, forcedexpiratory volume at 1 s; FVC, forced vital capacity. Unpaired Student�s t-test: *P < 0.05, compared to CRS– patients; **P < 0.05, compared to patients with CRS without NP.�Data presented as mean € SEM.
Table 2. Allergic and immunologic outcomes of BQ patients
BQ patients Normal values
OutcomesPositive nasal eosinophilia, n (%) 3 <1�Positive skin prick test to allergen, n (%) 20 20–30�Positive prick test to moulds, n (%) 9 6–12�Positive Aspergillus recombinant
allergens, n (%)3 Not described
Positive IgE to mould, n (%) 7 Not describedBlood eosinophils (%)� 3.5 € 0.3 <5�Blood eosinophils (cells/vol)� 0.26 € 0.02 <0.5�Positive AspergillusPrecipitins (%) 4.5 Not described
score (8.4 ± 0.4), especially for anterior rhinorrhea(1.9 ± 0.1), postnasal drip (1.8 ± 0.1) and nasalobstruction (1.6 ± 0.1), than patients with no CRS.
Patients with NP reported more reduction/loss of smell(77%; P < 0.001) compared to patients with no NP(30%), as well as higher total symptom scores, nasalobstruction and itching (Fig. 2).
Nasal polyp size
By nasal endoscopy, 22 patients (26%) with BQs hadmild-moderate nasal polyps (1.6 ± 0.1), of whom only32% of patients with NP had previously been diagnosed.The diagnosis of BQs had been performed 9 years earlierin patients with CRS (38 ± 2.5 years) than in thosewithout CRS (47 ± 4 years).
Sinusal occupancy
CT scan was affected in 66 patients (86%), with a score of6.6 ± 0.5, and a predominance of maxillary sinus(1.8 ± 0.1), ostiomeatal complex (1.7 ± 0.2) and ante-rior ethmoid sinus (1.5 ± 0.1). Patients that fulfilled theEP3OS criteria of CRS showed a total CT score of8.4 ± 0.4 (Fig. 3).
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Figure 1. Chest HRCT scan score (BQ severity) in patients withidiopathic or postinfectious bronchiectasis without (CRS–) andwith (CRS+) chronic rhinosinusitis. Unpaired Student�s t-test:***P < 0.001 compared to CRS– patients.
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Figure 2. Nasal symptom scores (Table 1in patients with bronchiectasis without (CRS–) and with (CRS+) chronic rhinosinusitis,and without (NP–) or with (NP+) nasal polyposis. (A) Total symptom score (TSS5), (B) anterior rhinorrhea, (C) postnasal drip, (D)nasal congestion/blockage, (E) loss of sense of smell and (F) facial pain/pressure. Unpaired Student�s t-test: *P < 0.05, **P < 0.01,***P < 0.001, compared to CRS– patients.
Patients with CRS mainly presented maxillary andethmoid opacification. Patients with CRS reported signif-icantly higher CT scores (P < 0001) than patients withoutCRS in: total score (8.4 ± 0.4 vs 0.7 ± 0.2), maxillary(2.1 ± 0.1 vs 0.4 ± 0.1), ostiomeatal complex (2.2 ± 0.2vs 0), anterior ethmoid (1.9 ± 0.1 vs 0.1 ± 0.1), posteriorethmoid (0.8 ± 0.1 vs 0.1 ± 0), frontal (0.5 ± 0.1 vs0.1 ± 0.1) and sphenoid (0.8 ± 0.1 vs 0) sinuses.Patients with NP presented significantly higher CT
scores (P < 0.05) than patients with no NP in: total score(10.8 ± 0.7 vs 7.3 ± 0.4), ostiomeatal complex(3.1 ± 0.2 vs 1.8 ± 0.2), posterior ethmoid (1.2 ± 0.2vs 0.7 ± 0.1), frontal (1 ± 0.2 vs 0.3 ± 0.1) andsphenoid (1.2 ± 0.2 vs 0.7 ± 0.1) sinuses.
Nasal function
Using anterior rhinomanometry, patients with CRSshowed a greater nasal obstruction (590 ± 37 cm3/s)compared to those with no CRS (854 ± 81.5 cm3/s;P < 0.01) (Fig. 4A) Acoustic rhinometry carried out onpatients with NP showed a significantly lower nasalvolume (13 ± 0.7 cm3) than those with no CRS(15 ± 0.8 cm3, P < 0.05) (Fig. 4B).
Inflammation markers
nNO was significantly lower in patients with NP(347 ± 62 ppb) compared to those with no CRS(683 ± 76 ppb, P < 0.001) and CRS with no NP(620 ± 47 ppb) (Fig. 4C). Nasal NO was inversely cor-related with the occupancy of the ostiomeatal complex
(R = )0.36; P < 0.01) in patients with NP. No differ-ences between groups were found on exhaled NOproduction (Fig. 4D).
CRS and nasal polyps in idiopathic vs postinfective bronchiectasis
We were interested in contrasting the results of patientswith postinfective with those classified as idiopathic. Nosignificant differences were observed between patientsdiagnosed with idiopathic and postinfective BQs, intotal symptoms score (6.9 ± 0.8 vs 7 ± 0.5), nasalpolyp prevalence (25% vs 25%) and the sinonasaloccupancy, as detected by the CT score (6.7 ± 1.1 vs6.0 ± 0.5). The only exception was olfaction, whichwas more affected in idiopathic bronchiectasis(1.08 ± 0.2 vs 0.5 ± 0.1). No significant differencesbetween idiopathic and postinfective BQs were found inallergic and immunologic studies, lung function, chestCT-scan, nasal function and inflammation markers(data not shown).
Discussion
The main findings of the present study are: (1) there is ahigh prevalence of CRS (77%) and NP (26%) in BQpatients (postinfective and idiopathic), (2) the severity ofBQ is related to the presence of CRS and NP, (3) thepercentage of patients with CRS and NP is similar inpostinfective and idiopathic BQ and (4) nasal NO isinversely correlated to the severity of CRS and thepresence of NP.
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Figure 3. Sinonasal CT occupancy in patients with bronchiectasis without (CRS–) and with (CRS+) chronic rhinosinusitis, andwithout (NP–) and with (NP+) nasal polyposis. (A) Total CT score, (B) maxillary sinus, (C) ostiomeatal complex, (D) anteriorethmoid sinus, (E) posterior ethmoid sinus, (F) sphenoid sinus and (G) frontal sinus. Unpaired Student�s t-test: **P < 0.01,***P < 0.001, compared to CRS– patients.
This is the first study that deeply examines and describesthe presence and extension of sinonasal pathology inpatients affected by stable BQs. Many studies haverelated upper and lower airway pathology and haveconfirmed a correlation between the degree of upper andlower airway inflammation in asthma (4) and COPD (4),but no studies have thoroughly assessed sinonasalpathology in stable bronchiectasis. Previous studiesobserved an increased prevalence of rhinosinusitis inpatients with BQs ranging from 58% to 70% (14, 19–21). However, the diagnostic criteria used in thesestudies were not clearly mentioned and, in some cases,the diagnosis was based only on symptoms and sinusalstandard X-ray. Because the assessment of CRS and NPwas made without using the support of CT scanning andendoscopy, the disease was imprecisely defined and its
extension poorly assessed. In one study, 47% of patientsreported a history of rhinosinusitis but the data on nasalsymptoms were not specified, while no sinonasalCT-scan or nasal endoscopy were not performed (20).Another recent study concluded that chronic rhinosi-nusitis was present in 70% of BQ patients (21). Thisstudy defined CRS as a chronic upper respiratory tractdisease present for more than a year, with commonsymptoms that vary from mild intermittent nasaldischarge to severe purulent sinusitis. Forty-sevenpercent of patients had sinus anomalies ranging frommucosal thickening to severe pan-sinusitis in a conven-tional radiological study. Other nasal symptoms presentin CRS, such as nasal obstruction and smell disorders,were not reported.
Currently, the European Academy of Allergologyand Clinical Immunology (EAACI) has publishedevidence-based recommendations on diagnosis and
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Figure 4. Nasal function measurements and nasal and bronchial inflammation measured by nitric oxide (NO) in patients with bronch-iectasis without (CRS–) and with (CRS+) chronic rhinosinusitis, and without (NP–) and with nasal polyposis (NP+). (A) Anteriorrhinomanometry, (B) acoustic rhinometry, (C) Nasal NO and (D) Exhaled NO. Unpaired Student�s t-test: *P < 0.05, **P < 0.01,***P < 0.001 compared to CRS– patients.
treatment: the EP3OS consensus (4). Clinical symptoms,endoscopic signs and/or CT changes persisting morethan 12 weeks define CRS, including nasal polyps. Inour study, 98% of patients with bronchiectasispresented nasal symptoms. Patients with BQs pre-sented anterior rhinorrhea, postnasal drip and nasalblockage as the major complaints, in accordance withthe major symptoms reported in EP3OS. An importantendoscopic sign, observed in more than 60% ofpatients, was mucous discharge from the middlemeatus. Using EP3OS criteria, 77% of patients withBQ presented CRS, while 25% presented mild tomoderate NP.C-reactive protein level was significantly increased in
patients with CRS, compared with patients with no CRS.Patients with NP were diagnosed with BQs more than10 years earlier than patients with no sinonasal pathol-ogy. Maxillary and ethmoid sinuses were mostly affectedin patients with CRS, either with or without NP, whilepatients with no NP had significant lower scores in CTthan patients with NP. Chest imaging (HRCT) is thegold-standard method for diagnosing BQ (22), and in ourstudy patients with CRS presented a significant increasein BQ imaging score, with no differences between CRS,with or without NP.All in all, these findings suggest that the presence of
CRS and NP in a patient with BQ is a marker of a moreactive and extended airway inflammatory process.
CRS and NP occur with similar frequency in idiopathic andpostinfectious bronchiectasis
A number of bronchiectasis is commonly consideredpostinfectious, mostly on the basis of a previous historyof severe pulmonary infections preceding the symptomsof bronchiectasis and radiological abnormalities. How-ever, the existence of either permanent bronchialdilatations before the infective episode or a defectivedefensive mechanism that precedes and/or accounts forboth the infective episode and the posterior develop-ment of bronchiectasis cannot be excluded as the originof some of these supposedly postinfective BQs. Weassumed that in the case of bronchiectasis resultingfrom a direct injury to the lower airways, the upperairways should remain preserved from any nasal andsinusal process. Conversely, and according to the unitedairway theory, most idiopathic BQs resulting from asyet unknown airway defensive or metabolic deficiencyshould be associated with upper airway diseases. Sincewe could not find significant differences between post-infectious and idiopathic bronchiectasis, in either theprevalence or the extension of CRS and NP, our resultssuggest that most of BQs considered as secondary todirect infectious injuries of the lower airways sharecommon mechanisms with idiopathic BQs.Nasal NO is inversely correlated to the occupation of
the ostiomeatal complex. In asthma patients, the ethmoi-
dal sinus is the most severely involved when CRS ispresent (23), while in our study, BQ patients show apredominant maxilo-ethmoidal involvement withobstruction of the ostiomeatal complex.
In healthy upper airways, nitric oxide is continuouslygenerated and secreted by the maxillary sinus through theostiomeatal complex and then diffuses into the nasalcavities (24). The ostiomeatal complex is a functional unitthat comprises maxillary sinus ostia, anterior ethmoidcells and their ostia, ethmoid infundibulum, hiatussemilunaris and middle meatus. NO has antiviral andantibacterial properties and plays a major role in innateimmunity.
It is known that nasal NO is increased in allergicrhinitis but the data on CRS and NP are controversial(25). A previous study found lower levels of nNO in CRSpatients than in healthy controls (26). Other studies alsoshow that nasal NO levels are inversely correlated withthe extent of NP, possibly related to the blockage of theostiomeatal complex (27, 28). nNO levels have also beenshown to inversely correlate with both the extent of theCT scan and the number of occluded paranasal sinuses(25, 27). In our study, nasal NO concentrations did notdiffer between groups, except in patients with NP, inwhom the nNO was found at lower concentrations, withan inverse correlation with the ostiomeatal complex CTscore.
Kharitonov et al. (29) have reported increased exhaledNO concentrations in BQ, in contrast with findings inother studies (30, 31). Our results concur with thosereporting no increase in exhaled NO in BQ.
In summary, almost four out of five patients with BQ(77%) presented criteria for CRS, and one out of everyfour patients had NP at nasal endoscopy (25%). Theseresults support the �united airways� concept and suggestthat most of the so-called postinfective bronchiectasisprobably result from as yet unknown processes thataffect the entire airways, rather than being the conse-quence of an injury (postinfectious and others) specifi-cally affecting only the lower airways. Finally, ourfindings also suggest that patients with BQ shouldalways be evaluated for CRS and NP, while patientswith CRS and NP should also be assessed for lowerairway diseases, including BQ.
Acknowledgments
Josep M Guilemany has been supported by the National Plan forScientific Research, Development and Technologic Innovation ofthe Health�s Institute Carlos III – Health Research Fund (CM06/00071), and the Spanish Society of Oto-Rhino-Laryngology, Head& Neck Pathology. The study has been partially sponsored by theFundacio Catalana de Pneumologia (FUCAP). Josep M Guilemanyand co-workers were awarded with the first prize on JMA posterpresentation for this study during the annual EAACI congress heldin Goteborg on June 2007.
1. Barker AF. Bronchiectasis. N Engl JMed 2002;346:1383–1393.
2. Guilemany JM, Alobid I, Angrill J,Ballesteros F, Bernal-Sprekelsen M,Picado C et al. The impact of bronchi-ectasis associated to sinonasal disease onquality of life. Respir Med 2006;100:1997–2003.
3. King P, Holdsworth S, Freezer N,Holmes P. Bronchiectasis. Intern Med J2006;36:729–737.
4. Fokkens W, Lund V, Mullol J, BachertC, Cohen N, Cobo R et al. EP3OS 2007:European position paper on rhinosi-nusitis and nasal polyps. Rhinology2007;20:1–136.
5. Kaliner MA, Osguthorpe JD, FiremanP, Anon J, Georgitis J, Davis ML et al.Sinusitis: bench to bedside. Currentfindings, future directions. J Allergy ClinImmunol 1997;99:s829–s848.
6. Gordts F, Clement PAR, Buisseret T.Prevalence of sinusitis signs in a non-ENT population. Otorhinolaringology1996;58:315–319.
7. Benitez P, Alobid I, de Haro J,Berenguer J, Bernal-Sprekelsen M,Pujols L et al. A short course of oralprednisone followed by intranasalbudesonide is an effective treatment ofsevere nasal polyps. Laryngoscope2006;116:770–775.
8. ten Brinke A, Grootendorst DC,Schmidt JT, De Bruine FT, van BuchemMA, Sterk PJ et al. Chronic sinusitis insevere asthma is related to sputumeosinophilia. J Allergy Clin Immunol2002;109:621–626.
9. Alobid I, Benıtez P, Bernal-SprekelsenM, Roca J, Alonso J, Picado C et al.Nasal polyposis and its impact onquality of life. Comparison between theeffects of medical and surgical treat-ments. Allergy 2005;60:452–458.
10. Haave E, Hyland ME, Skumlien S. Therelation between measures of healthstatus and quality of life in COPD.Chron Respir Dis 2006;3:195–199.
11. Roberts NJ, Lloyd-Owen SJ, Rapado F,Patel IS, Wilkinson TM, Donaldson GCet al. Relationship between chronicnasal and respiratory symptoms inpatients with COPD. Respir Med 2003;97:909–914.
12. Hens G, Vanaudenaerde BM, BullensDM, Piessens M, Decramer M, DupontLJ et al. Allergy 2008;63:261–267.
14. Angrill J, Agusti C, de Celis R, Rano A,Gonzalez J, Sole T et al. Bacterial col-onisation in patients with bronchiecta-sis: microbiological pattern and riskfactors. Thorax 2002;57:15–19.
15. Valero A, Serrano C, Valera JL,Barbera A, Torrego A, Mullol J et al.Nasal and bronchial response to exercisein patients with asthma and rhinitis: therole of nitric oxide. Allergy 2005;60:1126–1131.
16. Rasp G, Schuk A, Kastenbauer ER. Anew grading system for nasal polyps ofthe ethmoid bone. HNO-online 1996.http://www.link.springer.de/link//service//journals/00106.
17. Lildholdt T, Rundcrantz H, LindqvistN. Efficacy of topical corticosteroidpowder for nasal polyps: a double-blind,placebo-controlled study of budesonide.Clin Otolaryngol 1995;20:26–30.
18. Lund VJ, MacKay IS. Staging in rhino-sinusitus. Rhinology 1993;31:183–184.
19. King PT, Holdsworth SR, Freezer NJ,Villanueva E, Holmes PW. Characteri-sation of the onset and presenting clini-cal features of adult bronchiectasis.Respir Med 2006;100:2183–2189.
20. Pasteur MC, Helliwell SM, HoughtonSJ, Webb SC, Foweraker JE, CouldenRA et al. An investigation into causa-tive factors in patients with bronchiec-tasis. Am J Respir Crit Care Med2000;162:1277–1284.
21. Smith IE, Jurriaans E, Diederich S, AliN, Shneerson JM, Flower CD. Chronicsputum production: correlationsbetween clinical features and findings onhigh resolution computed tomographicscanning of the chest. Thorax 1996;51:914–918.
22. Judge EP, Dodd JD, Masterson JB,Gallagher CG. Pulmonary abnormali-ties on high-resolution CT demonstratemore rapid decline than FEV1 in adultswith cystic fibrosis. Chest 2006;130:1424–1432.
23. Hun-Jong D, Hyo Yeol K, Young-JunC, Tae Wook K, Joon Ho K, Seung-Kyu C et al. Computed tomographicassessment of chronic rhinosinusitis withasthma. Am J Rhinol 2006;5:450–452.
24. Lundberg JO, Rinder J, Weitzberg E,Lundberg JM, Alving K. Nasallyexhaled nitric oxide in humans origi-nates mainly in the paranasal sinuses.Acta Physiol Scand 1994;152:431–432.
25. Ragab SM, Lund VJ, Saleh HA,Scadding G. Nasal nitric oxide inobjective evaluation of chronic rhino-sinusitis therapy. Allergy 2006;61:717–724.
26. Lindberg S, Cervin A, Runer T. Nitricoxide (NO) production in the upperairways is decreased in chronic sinusitis.Acta Otolaryngol 1997;117:113–117.
27. Arnal JF, Flores P, Rami J, Murris-Espin M, Bremont F, Pasto I et al.Nasal nitric oxide concentration inparanasal sinus inflammatory diseases.Eur Respir J 1999;13:307–312.
28. Colantonio D, Brouillette A, Parikh A,Scadding GK. Paradoxical low nasalnitric oxide in nasal polyposis. Clin ExpAllergy 2002;32:698–701.
29. Kharitonov SA, Wells AU, O¢ConnorBJ, Cole PJ, Hansell DM, Logan-Sinclair RB et al. Elevated levels ofexhaled nitric oxide in bronchiectasis.Am J Respir Crit Care Med 1995;151:1889–1893.
30. Narang I, Ersu R, Wilson NM, Bush A.Nitric oxide in chronic airway inflam-mation in children: diagnostic use andpathophysiological significance. Thorax2002;57:586–589.
31. Foley SC, Hopkins NO, Fitzgerald MX,Donnelly SC, McLoughlin P. Airwaynitric oxide output is reduced in bron-chiectasis. Respir Med 2007;101:1549–1555.
32. Colas C, Chivato T, Dıaz de Rojas F,Lleonart R, Nieto A, Pelaez Aet al. Alergologica 2005. Factoresepidemiologicos, clınicos ysocioeconomicos de las enfermedadesalergicas en Espana en 2005 (SEAIC).Vol. 5. Madrid: ed. Luzan, 2006.
Estudio 2. The impact of bronchiectasis associated to sinonasal disease on
quality of life. Respir Med 2006;100:1997-2003. DOI: 10.1016/j.rmed.2006.02.016
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Respiratory Medicine (2006) 100, 1997–2003
0954-6111/$ - sdoi:10.1016/j.r
�CorrespondiE-mail addr
The impact of bronchiectasis associated tosinonasal disease on quality of life
J.M. Guilemanya,�, I. Alobida,b, J. Angrillc, F. Ballesterosa,M. Bernal-Sprekelsena, C. Picadoc, J. Mullola,d
aRhinology Unit, Department of Otorhinolaryngology, Hospital Clinic de Barcelona, ENT, Barcelona, SpainbDepartment of Otorhinolaryngology, Hospital Municipal de Badalona, Badalona, SpaincDepartment of Pneumology, Hospital Clınic, Department of Medicine, University of Barcelona, SpaindInstitut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Received 20 September 2005; accepted 19 February 2006
KEYWORDSBronchiectasis;Nasal polyposis;Quality of life;SF-36 questionnaire
SummaryBackground: Bronchiectasis (BQs) is an uncommon disease with the potential tocause devastating complications. All patients with BQs have cough and chronicsputum production that may have a great impact on patient’s quality of life. Upperairway symptoms are also frequent in patients with BQs. Associations between upperand lower airways diseases have been demonstrated in allergic rhinitis and asthma,nasal polyposis and asthma, chronic obstructive lung disease and chronicrhinosinusitis.Objective: (1) To investigate the impact of bronchiectasis and nasal symptoms onquality of life. (2) To evaluate the added impact of nasal polyposis on quality of lifein patients with BQs.Methods: Sixty patients with bronchiectasis and upper airway symptoms wereincluded. Patients were evaluated for nasal symptoms, nasal polyp size byendoscopy, and quality of life using the SF-36 generic questionnaire.Results: In comparison with the Spanish general population, patients with BQs hadworse scores in all SF-36 domains (Po0.05). Males reported significantly higherquality of life scores on physical functioning and social functioning than females did.Although the age, pulmonary function, presence of nasal polyps, upper airwaysymptoms, tobacco smoking history, and disease duration was similar between them.Males with BQs had worse quality of life than males from the Spanish generalpopulation on body pain, general health, and vitality (Po0.05). Females with BQshad worse quality of life than females from the Spanish general population onphysical function, body pain, general health, vitality, social function, and emotionalrole (Po0.05). Nasal polyps were found in 25 (41.6%) of 60 patients with BQs.
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No significant differences were observed on quality of life outcomes betweenpatients with BQs with and without nasal polyposis.Conclusion: These results suggest that BQs has a considerable impact on quality oflife while nasal polyposis has no additional impact on the quality of life of patientswith BQs.& 2006 Elsevier Ltd. All rights reserved.
Introduction
Bronchiectasis (BQs) consists of a permanent andirreversible destruction and dilatation of bronchiand bronchioles due to retained secretions andrecurrent infections that cause inflammation, ob-struction, and damage of the lower airway. BQs area consequence of a variety of different diseaseswhere infection and obstruction appears to be themost important contributory factors. BQs arefrequently associated with cystic fibrosis, primaryciliary dyskinesia, immunodeficiency, rheumatoidarthritis, and inflammatory bowel disease.1
Nasal polyposis (NP) is a chronic inflammatorydisease of the nose and sinus mucosa that, despitediffering hypotheses of its cause, remains poorlyunderstood.2,3 NP can lead to progressive nasalobstruction, loss of smell, rhinorrhea, and sneez-ing. NP is frequently associated with asthma andother pulmonary disorders such as cystic fibrosis,primary ciliary dyskinesia, and aspirin sensitivity.4,5
BQs is a disease with the potential to causedevastating complications. The patients with BQshave cough and chronic sputum production thathave a great impact on patient’s quality of life(QoL). Most patients undergo slow and progressivehealth deterioration over decades. It can havedetrimental effects on physical, psychological, andsocial aspects of the patient0s life, significantlyworsening the patient’s QoL. The lung functiondoes not reflect the impact of the disease in thepatient0s health status and thus should be supple-mented using QoL questionnaires.6 However, theimpact of BQs to patients’ general health status hasnot been reported for the Spanish patients. Gen-erally, there are two major types of QoL instru-ments used in clinical trials: specific and generic.Specific questionnaires are usually focused on oneparticular area such as a disease state, a selectedpopulation, or a certain function or problem. TheSt. George Respiratory Questionnaire (SGRQ) hasbeen used to assess the QoL in patients withasthma, COPD, a1-antitrypsin deficiency, intersti-cial lung diseases and BQ.7
Generic QoL questionnaires are also availableand may be administrated to any individual,
thereby making it possible to assess the burden ofillness in different conditions. The Short Form-36Health Survey (SF-36) is the most widely usedgeneric instrument to measure health status. Thisquestionnaire has been recently adapted for theSpanish-speaking general population according tothe International Quality of Life Assessment (IQO-LA) project showing a good reproducibility andvalidity.8–10
The aims of this study were: (1) to investigatethe impact of BQs and nasal symptoms on QoLcompared with the Spanish general populationusing the SF-36 questionnaire; and (2) to evaluatethe additional impact of mild-moderate nasalpolyposis on QoL in patients with BQs.
Material and methods
Study population: sixty patients with non-cysticfibrosis BQs in a stable phase of their illnes withupper airways symptoms were included in thisprospective study from April 2002 to July 2004.
Design: the diagnosis of BQs was based onsymptoms, physical findings, and thoracic high-resolution CT scan. Stability of the BQs conditionwas assessed with a complete clinical evaluation, aforced spirometry, and if is necessary a thoraxradiology. Stable BQs condition was defined as theabsence of fever, no impairment of airflow limita-tion, no increase in sputum overproduction orchange of the macroscopic characteristics (puru-lent), and no increase in chronic cough. Insummary, no increase in respiratory symptoms ormodifications in the treatment over the previous 6weeks. The day of the study, a complete clinicalevaluation and a forced spirometry (Collins SurveyIII, plus, USA) were performed. Exclusion criteriawere hospitalization in the previous 2 months, useof antibiotics in the last 4 weeks or presence of aserious concomitant illness.
The diagnosis of nasal polyposis was based on thevisualization of bilateral polyps under nasal endo-scopic examination. Approval for the study wasobtained from the Ethic’s Committee of ourinstitution and a signed informed consent wasobtained from all patients.
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The impact of bronchiectasis 1999
After a 4-week washout period of oral andintranasal steroids, all patients with BQs completedthe SF-36 survey. Nasal symptoms and nasalendoscopy were also scored. Most of experimentalstudies and clinical trails investigating nasal poly-posis consider adequate a washout period of 4weeks since patients with sinonasal pathology oftenfollow treatments with oral antihistamines, oraland intranasal corticosteroids, oral antibiotics, andnasal lavages that may improve the clinicalsymptoms.11,12
Quality of life: the Health Survey SF-36 consistsof 36 self-administered questions and was devel-oped to measure eight health domains: physicalfunctioning (PF), role physical (RP), bodily pain(BP), general health (GH), vitality (VT), roleemotional (RE), social functioning (SF), and mentalhealth (MH). Two summary scales are also included:the physical component summary (PCS) and themental component summary (MCS). Spanish versionof the SF-36 Health Survey was used. This version isvery similar to the original US questionnaire inabsolute values, age and gender. We needed ageneric questionnaire to assess QoL in pathologypotentially involved both upper and lower airways:bronchiectasis and sinonasal pathology (with orwithout nasal polyposis). Scale scores in eachdomain and summaries range from 0 to 100, higherscores indicating better QoL.13
Nasal symptoms: obstruction, loss of the sense ofsmell, rhinorrhea (anterior and posterior), facialpain, itching, and sneezing was scored. The severityof nasal symptoms was assessed and scored, follow-ing the system designed by Rasp et al.,14 andpublished before11,12 by our group, as follows: 0, nosymptom; 1, mild but not troublesome symptom; 2,moderate symptom somewhat troublesome but notenough to interfere with daily activities or sleep;and 3, severe and troublesome symptom thatinterferes with daily activities or sleep.
Nasal endoscopy: polyp size was scored from 0 to3 for each nasal cavity following Lildholdt0sclassification: 0, no polyps; 1, mild polyposis (smallpolyps not reaching the upper edge of the inferiorturbinate); 2, moderate polyposis (polyps betweenthe upper and lower edges of the inferior turbi-nate); 3, severe polyposis (large polyps reachingthe lower edge of the inferior turbinate).15,16 Allpatients had upper airway symptoms and wereexamined by the same otorhinolaryngologist at theDepartment of Otolaryngology of our Hospital.
Lung function: evaluated by forced spirometryaccording to standard methods. The best one-second forced expiratory volume (FEV1) was chosenfor analysis and expressed as percent predictedFEV1 (FEV1%).
Statistical analysis: was performed using SPSS forWindows (SPSS 11.0, Chicago, IL, USA). All analyseswere performed using two-tailed tests significanceat the 0.05 level. The data are presented asmean7SD (standard deviation). All data wereassesed for normal distribution and the Bonferronicorrection for multiple comparisons was used. Ourfirst objective was to investigate the impact of BQsand nasal symptoms on QoL compared with theSpanish general population using the SF-36 ques-tionnaire. A study population size of 29 patients pergroup, achieves 95% power to detect a differenceof 20% between the null hypothesis mean of 82.7(PCS) and the alternative hypothesis mean of 66.4with an estimated standard deviation of 23.3 andwith a significance level (alpha) of 0.05 using a two-sided one-sample t-test.
Unpaired Student’s t test was used to comparenasal symptoms and SF-36 scores of patients withBQs with those from the Spanish general popula-tion, and between patients with or without NP. SF-36 scores for healthy control subjects from theSpanish population used in comparative analyseswere derived from a sample of 9984 people ofwhom 51.8% were females. Males of the Spanishgeneral population have demonstrated significanthigher scores than females in all SF-36 dimensions.7
After analyzing matching for age, no significantdifference on the mean age between patients ofour study and the Spanish general population.
Pearson correlation coefficients were used toexamine the association between QoL scores andgender, age, nasal symptoms, nasal polyps, andlung function. Multiple linear regression analysiswith SF-36 scores were used, alternatively the PCSand MCS scores as the dependent variable and age,sex, nasal polyps size as independent variables.Internal consistency was calculated by Cronbach’s acoefficient for each SF-36 scale. This coefficientranges from 0 to 1, and a minimum coefficient of0.7 is recommended to ensure a good internalconsistency.17
Results
The mean age of patients with BQs was 52716years (ranging from 18 to 78 years). Thirty-ninepatients (65%) were female (Table 1). Patients withBQs scored anterior and posterior rhinorrhea, lossof the sense of smell, and nasal obstruction as themajor complaints, while itching, facial pain andsneezing were much less frequent and discomfort-ing (Table 2).
Twenty-five patients (41.6%) with BQs had nasalpolyps with a size score of 1.570.4 with a range(1–2).15 The patients distribution by lildholdt is:
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Table 1 Characteristics of patients with bronchiectasis (BQs).
Table 2 Nasal symptoms in patients with bronchiectasis (BQs).
N Nasalobstruction
Loss of sense ofsmell
Anteriorrhinorrhea
Posteriorrhinorrhea
Sneezing
All patientswith BQs
60 1.6570.9 0.971 1.970.9 1.870.9 1.271
BQs without NP 35 1.470.8 0.570.8 1.870.9 1.970.9 1.270.9BQs with NP 25 2.0570.8y 1.471.0y 270.8 1.770.9 1.271
Nasal symptoms and polyp size were scored from 0 to 3. yPo0.05, compared to patients with bronchiectasis without nasalpolyposis.
0
20
40
60
80
100
PF RP BP GH VT SF RE MH PCS MCS
Spanish population
All BQs
without NP
with NP
**
**
**
*
*
*
*
SF-36 domains
Scor
e
Figure 1 Quality of life in patients with bronchiectasisand sinonasal disease compared to the Spanish generalpopulation. Physical functioning (PF), role physicalfunctioning (RP), bodily pain (BP), general health (GH),vitality (VT), social functioning (SF), role emotionalfunctioning (RE), mental health (MH), mental componentsummary (MCS), and physical component summary (PCS).All patients (with and without polyps) had significantlyworse scores in all SF-36 domains. Unpaired student’s ttest was used, *Po0.05.
J.M. Guilemany et al.2000
Lildholdt 1: 8 patients; Lildholdt 1.5: 10 patients(a NP punctuation of 2 in a fossa and 1 in the other);Lildholdt 2: 7 patients. Patients with BQ and NPhad higher scores (Po0.05) of nasal obstructionand loss of sense of smell than patients with BQwithout NP.
In comparison with the Spanish general popula-tion,8 patients with BQs had significantly (Po0.05)worse QoL scores in all SF-36 domains (Fig. 1) aswell as in MCS and PCS (Table 3). No significantdifferences on QoL of patients with BQs and NP orwithout NP were observed.
Females showed lower physical functioning (dif-ference: 13.1, Po0.05 and 95%CI: 1.7–24.5), andlower social functioning (difference: 15.7, Po0.05and 95%CI: 0.4–31) than males. Females withBQs had lower scores of QoL (Po0.05) thanfemales from the Spanish general population onphysical functioning, body pain, general health,vitality, social functioning, and role emotional.Males with BQs also showed lower scores of QoL(Po0.05) than males from the Spanish generalpopulation on body pain, general health, andvitality. No significant differences were observedbetween males and females on age, pulmonaryfunction, presence of nasal polyps, upper airwaysymptoms, tobacco smoking history, and diseaseduration. Analysis of internal consistencies for allSF-36 domains showed a Cronbach’s a value higherthan 0.7 (0.75–0.91). Age, nasal symptoms, andpolyp size score were not statistically correlated toSF-36 scores.
Patients showed a degree of pulmonary functionimpairment on the FEV1% (8173.4). There were nosignificant correlation between the two QoL sum-maries and the degree of pulmonary function are:SCF (r: 0.21; P ¼ 0:242) and SCM (r: 0.095;P ¼ 0:599). Multiple linear regression analysis with
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Table 3 Quality of life domains and summary data of patients with bronchiectasis and sinonasal disease.
�Po0.05 bronchiectasis with nasal pathology compared to the Spanish general population.
The impact of bronchiectasis 2001
SF-36 scores were used, alternatively the PCS andMCS scores as the dependent variable and age, sex,nasal polyps size as independent variables withoutsignificant results.
Discussion
No studies have reported the impact of BQ andupper airway disease on QoL using the SF-36questionnaire. The main findings of our study were:(1) patients with BQ have an impaired QoL whencompared to the Spanish general population; (2)nasal polyposis has no additional impact on QoL inpatients with BQs.
This study demonstrates that QoL in patients withBQ is impaired compared to the general populationsin all SF-36 domains. No associations between QoLand age, nasal symptoms, and polyp size wereobserved. Furthermore, our findings supported thedeveloper’s claim of internal consistency for the SF-36 questionnaire since all the coefficients were atvalues above those recommended.
This study also demonstrates that women withBQ report poorer QoL scores on physical functioningand social functioning than males. Using the SF-36questionnaire, Bousquet et al. have observed thatmales with asthma report higher QoL scores thanfemales with asthma.18 Gender-related differencesin response to a chronic disease such as asthma isimportant in tailoring an education and manage-ment plan to each individual patient.19 Allergicrhinitis and asthma usually coexist. Patients withboth diseases experience more physical limitationsthan patients with allergic rhinitis alone, but nodifferences were found between these two groupsfor concepts related to social/mental health.20
Cystic fibrosis is the most common autosomalrecessive disease with fatal outcome in Caucasians
due to chronic infection of the lung resulting infibrosis and bronchiectasis followed by respiratoryinsufficiency. Some differences emerged betweenmales and females, with females generally report-ing poorer QoL scores. Evidence indicated thatmales and females perceived their health statusdifferently, with females having a more accurateperception of objective clinical health status.21
The St. George Respiratory Questionnaire (SGRQ)is a self-administrated health-related QoL measurecontaining 50 items and 76 weighted responsesdivided into three components: symptoms, activity,and impacts. The SGRQ has been used to assess theQoL in patients with asthma, COPD, a1-antitrypsindeficiency,22–25 and more recently BQ.26 Anxietyand depression are quite common in patients withBQ.27 QoL measured by the SGRQ in patients withBQ assessing the pulmonary function and thepresence of colonization (with pseudomonas orother microorganisms) shows that patients with BQcolonized with pseudomonas have worse pulmonaryfunction and QoL than uncolonized patients. More-over, patients having microorganisms other thanpseudomonas have a worse QoL than those withoutmicroorganisms.28 Pseudomonas aeruginosa is themost relevant pathogen producing chronic lunginfections in patients with chronic underlyingdiseases such as cystic fibrosis (CF), bronchiectasis,and chronic obstructive pulmonary disease (COPD).Hypermutation of pseudomona is found to be a keyfactor for the development of multiple-antimicro-bial resistance, and therefore these findings areexpected to have important consequences for thetreatment of chronic infections.29,30
Chronic rhinosinusitis (CRS) is an inflammatorydisease of the mucosa of the nasal cavity andparanasal sinuses with symptoms lasting longerthan 12 weeks. Currently, it is unclear, whetherCRS with NP and CRS without NP represent different
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disease entities or just different stages of onesingle disease. Recent evidence suggests that,despite clinical similarities, CRS with and withoutNP have different inflammatory pathways andcytokine profiles. Although the similar clinicalsymptoms found in these patients, the greatclinical differences probably remains in the inten-sity on nasal obstruction and smell disorders.31
Nasal polyps are often an indicative of airwaydisease involving both the upper and lower respira-tory tracts.32 Radenne et al.33 has investigated theimpact of NP in QoL demonstrating that nasal polypsimpaired QoL in all SF-36 domains. More recently ourgroup demonstrated that asthma but not aspirinsensitivity has an additional negative impact on theQoL of patients with NP.11 QoL improved after NPtreatment, the improvement being related to nasalsymptoms. Both medical and surgical treatment ledto similar effects in improving QoL.12,34 Gliklich andMetson35 assessed the burden of chronic rhinosinusitisby using the SF-36 questionnaire and demonstrated asignificant decrease in body pain, general health,vitality, and social functioning domains comparedwith the American general population. Using the SF-36, other studies have also demonstrated thatchronic rhinosinusitis has a considerable impact onall SF-36 domains except for physical functioning andcompared with a healthy population.36–38
Patients with NP had lower scores in all SF-36domains except for physical functioning and roleemotional than patients with coronary arterydisease,39 chronic obstructive pulmonary disease,9
and asthma.40
In the present study patients with BQ and mild-moderate NP (Lildholdt classification o1.5), showedno further negative impact on QoL. The three mostdisabling symptoms were anterior rhinorrhea, pos-terior rhinorrhea and nasal obstruction. This studyprovides additional evidence that the degree ofabnormality on nasal symptoms is not associatedwith impairment of QoL. Patients with nasal polypshad a higher nasal obstruction and loss of sense ofsmell that did provoke no significant differences onQoL compared to patients without NP.
In conclusion, these results suggest that BQ has aconsiderable impact on QoL, but that nasal polypshave no additional impact on QoL of patients withBQ. Further studies are needed to better under-standing of the association between the upper andlower airways diseases.
Acknowledgements
The authors are grateful for Dr. Jordi Alonso of theHealth Services Research Unit, Institut Municipald0Investigacio Medica (IMIM-IMAS) of Barcelona, and
for Llorenc- Quinto of the Statistic Department inour Hospital, for their comments that greatlyimproved the presentation of the paper.
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13. Ware JE, Konsinski M, Keller SD. SF-36 Physical and mentalhealth summary scales: a user’s manual. Boston, MA: TheHealth Institute, New England Medical Center; 1994.
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15. Lildholdt T, Rundcrantz H, Lindqvist N. Efficacy of topicalcorticosteroid powder for nasal polyps: a double-blind,placebo-controlled study of budesonide. Clin Otolaryngol1995;20:26–30.
16. Johansen LV, Illum P, Kristensen S, Winther L, Petersen SV,Synnerstad B. The effect of Budesonide (Rhinocorts) in thetreatment of small and medium sized nasal polyps. ClinOtolaryngol 1993;18:524–7.
17. Cronbach LJ. Coefficient alpha and internal structure of atest. Psychometrika 1951;16:297–334.
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21. Gee L, Abbott J, Conway SP, Etherington C, Webb AK.Quality of life in cystic fibrosis: the impact of gender,general health perceptions and disease severity. J CystFibros 2003;2:206–13.
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26. Wilson CB, Jones PW, O’Leary CJ, Cole PJ, Wilson R.Validation of the St. George’s Respiratory Questionnaire inbronchiectasis. Am J Respir Crit Care Med 1997;156:536–41.
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28. Hernandez C, Abreu J, Jimenez A, Fernandez R, Martin C.Pulmonary function and quality of life in relation tobronchial colonization in adults with bronchiectasis notcaused by cystic fibrosis. Med Clin (Barc) 2002;118:130–4.
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31. Gillespie MB, Osguthorpe JD. Pharmacologic management ofchronic rhinosinusitis, alone or with nasal polyposis. CurrAllergy Asthma Rep 2004;4:478–85.
32. Johansson L, Bramerson A, Holmberg K, Melen I, Akerlund A,Bende M. Clinical relevance of nasal polyps in individualsrecruited from a general population-based study. ActaOtolaryngol 2004;124:77–81.
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34. Alobid I, Benıtez P, Pujols L, Maldonado M, Bernal-Sprekelsen M, Morello A, et al. Severe nasal polyposis andits impact on quality of life. The effect of short course oforal steroids followed by long term intranasal steroidstreatment. Rhinology 2006;44:8–13.
35. Gliklich RE, Metson R. Effect of sinus surgery on quality oflife. Otolaryngol Head Neck Surg 1997;117:12–7.
36. Winstead W, Barnett S. Impact of endoscopic sinus surgeryon global health perception: an outcomes study. OtolaryngolHead Neck Surg 1998;119:486–91.
37. Durr DG, Desrosiers MY, Dassa C. Quality of life in patientswith rhinosinusitis. J Otolaryngol 1999;28:108–11.
38. Wang PC, Tai CJ, Lin MS, Chu CC, Liang SC. Quality of life inTaiwanese adults with chronic rhino-sinusitis. Qual Life Res2003;12:443–8.
39. Failde I, Ramos I. Validity and reliability of the SF-36 healthsurvey questionnaire in patients with coronary arterydisease. J Clin Epidemiol 2000;53:359–65.
40. Espinosa De Los Monteros MJ, Alonso J, Ancochea J,Gonzalez A. Quality of life in asthma: reliability and validityof the short form generic questionnaire (SF-36) applied tothe population of asthmatics in a public health area. ArchBronconeumol 2002;38:4–9.
Tesis Doctoral III. Trabajo Experimental
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Estudio 3. United airways: the impact of chronic rhinosinusitis and nasal
polyps in bronchiectasic patient’s quality of life. Allergy 2009;64:1524-9. DOI:10.1111/j.1398-9995.2009.02011.x
Original article
United airways: the impact of chronic rhinosinusitis and nasal
polyps in bronchiectasic patient�s quality of life
Bronchiectasis (BQ) consists of a permanent and irrevers-ible dilatation of bronchi and bronchioles caused byretained secretions and recurrent infections that causeinflammation, obstruction, and damage of the lowerairway. Bronchiectasis is a consequence of a variety ofdifferent diseases inwhich airway infection andobstructionappear to be the most important contributory factors.Bronchiectasis is frequently associated with cystic fibrosis,primary ciliary dyskinesia, immunodeficiency, rheumatoidarthritis, and inflammatory bowel diseases (1).Chronic rhinosinusitis (CRS), one of the most common
chronic diseases (2), is an inflammatory disease of the
nose and sinus mucosa that is still little understood,despite various hypotheses about its cause (3). Chronicrhinosinusitis with nasal polyps (NP) is considered asubgroup of CRS. Chronic rhinosinusitis with or withoutNP is often taken together as one disease entity, becauseit seems impossible to clearly differentiate both entities(4–6). The reason why polyps develop in some patientsand not in others remains unknown. In the generalpopulation, the prevalence of NP is 4%. Although thecause of NPs is still unknown, it has been reported to beassociated with asthma and other pulmonary disorders,such as cystic fibrosis, primary ciliary dyskinesia, aspirin
Background: The nose and the bronchi belong, in anatomical and physiopath-ological terms, to the concept of united airways. Associations between upper andlower airways diseases have been demonstrated in allergic rhinitis and asthma,nasal polyposis (NP) and asthma, chronic rhinosinusitis (CRS) and chronicobstructive pulmonary disease, and more recently CRS/NP and bronchiectasis(BQ).Objective: To evaluate the impact of CRS on quality of life (QoL) of patientswith BQ, and to correlate these findings with the pulmonary status, nasalsymptoms, and general health status.Methods: In a prospective study, patients with BQ (n = 80) were evaluated forCRS and NP using EP3OS criteria, and severity of BQ using chest highresolution computed tomography (HRCT)-scan. Quality of life was assessed inall patients by using specific [Sinonasal Outcome Test-20 (SNOT-20), St GeorgeRespiratory Questionnaire (SGRQ)], and generic (Short Form-36; SF-36)questionnaires.Results: Using SNOT-20, patients with CRS had worse QoL (2.1 ± 0.1;P < 0.001) than patients without CRS (0.4 ± 0.06). Using SGRQ total score,patients with CRS had worse QoL (43.7 ± 2.2; P < 0.001) than patientswithout CRS (24.7 ± 2.5). Using SF-36, patients with CRS had worse QoL,both in the physical summary (64 ± 3.4; P < 0.05) and the mental summary(65.5 ± 4.7; P < 0.05), than patients without CRS (physical summary [PS]:76.2 ± 3.3; mental summary [MS]: 78.3 ± 5.3, respectively). SinonasalOutcome Test-20 was correlated with SGRQ total score (r = 0.72; P < 0.01),and SF-36 physical summary (r = )0.63; P < 0.01). St George RespiratoryQuestionnaire was correlated with SF-36 on physical summary (r = )0.58;P < 0.05) and with forced expiratory volume in 1 s (r = )0.41; P < 0.05).Conclusion: These results suggested that CRS, measured by both specific andgeneric questionnaires, has a considerable impact on the QoL of patients withBQ.
J. M. Guilemany1,5, J. Angrill2,I. Alobid1,5, S. Centellas1,5, E. Prades1,J. Roca1,4,5, L. Pujols1,5, M. Bernal-Sprekelsen1,5, C. Picado2,3,5,*,J. Mullol1,3,4,5,*1Rhinology Unit and Smell Clinic, Department ofOtorhinolaryngology, Hospital Cl�nic i Universitari,Barcelona; 2Pneumology and Respiratory Allergy,Hospital Cl�nic, Barcelona; 3Department ofMedicine, University of Barcelona, Barcelona;4Institut d�Investigacions Biom�diques August Pi iSunyer (IDIBAPS), Barcelona; 5Centro deInvestigaci�n Biom�dica en Red de EnfermedadesRespiratorias (CIBERes), Barcelona, Spain
Key words: bronchiectasis; chronic rhinosinusitis; nasalpolyposis; quality of life; Short Form-36 questionnaire;St George Respiratory Questionnaire; SinonasalOutcome Test-20.
Jos� Mara Guilemany TosteDepartment of OtorhinolaryngologyHospital Cl�nic i Universitaric/Villarroel, 17008036 BarcelonaCataloniaSpain
*Both senior investigators participated with equalresponsibilities.Hospital Cl�nic – IDIBAPS is a partner center ofGA2LEN (Global Allergy and Asthma EuropeanNetwork).
Accepted for publication 29 January 2009
Allergy 2009: 64: 1524–1529 � 2009 John Wiley & Sons A/S
DOI: 10.1111/j.1398-9995.2009.02011.x
1524
sensitivity (7, 8), and more recently BQ (9). Almost fourout of five patients with BQ (77%) presented criteria forCRS, and one out of every four patients had NP on nasalendoscopy (25%) (9).Bronchiectasis is a disease with the potential to cause
devastating complications. The patients with BQ presentcough and chronic sputum production, which have agreat impact on patient�s quality of life (QoL) (10). Mostpatients undergo slow and progressive health deteriora-tion over decades. Chronic rhinosinusitis and BQ canhave detrimental effects on physical, psychological, andsocial aspects of patients� lives, significantly worseningtheir QoL. Symptoms and lung function do not reflect theimpact of the disease on the patient�s health status, whichshould be supplemented by the use of QoL questionnaires(11). Studies have reported that patients with CRS havemore bodily pain (BP) and worse social functioning (SF)than for example patients with chronic obstructivepulmonary disease (COPD), congestive heart failure,diabetes, and back pain (12, 13).There are two major types of QoL instruments used in
clinical trials: specific and generic questionnaires (14, 15).Specific questionnaires are usually focussed on oneparticular area such as a disease state, a selectedpopulation, or a certain function or problem. The StGeorge Respiratory Questionnaire (SGRQ) has beenused to assess the QoL in patients with asthma, COPD,a1-antitrypsin deficiency, interstitial lung diseases, andBQ (16). The Sinonasal Outcome Test (SNOT-20) is alsoa validated, disease-specific, health-related QoL question-naire for upper airway pathology (17). This has been usedin a number of studies of CRS (18, 19). Rhinosinusitis-related impairment of QoL was assessed with theSNOT-20 questionnaire in allergic asthmatic, nonallergicasthmatic, and COPD patients. Patients with allergic andnonallergic asthma and COPD show increased nasalsymptoms, more nasal inflammation, and significantimpairment of their QoL related to rhinosinusitis (20).No studies have reported the impact of upper airwaydisease on QoL in patients affected by BQ on the basis ofspecific questionnaires such as SNOT-20 and SGRQ.Generic QoL questionnaires are also available and
may be administrated to any individual, thereby makingit possible to assess the burden of illness in variousconditions. The Short Form-36 Health Survey (SF-36) isthe most widely used generic instrument for measuringhealth status. This questionnaire has been adapted forthe Spanish-speaking general population in accordancewith the International Quality of Life Assessmentproject and has demonstrated a good reproducibilityand validity (21–23). In a previous study performed byour group with SF-36, we demonstrated that patientswith BQ and CRS have a significantly impaired QoLcompared with the Spanish general population with nodifferences between CRS, either with or without NP(24). The aim of this study was to evaluate the impact ofCRS, with or without NP, on the QoL of patients with
BQ using a specific QoL questionnaire (SNOT-20,SGRQ), and to correlate the findings with: SF-36, nasalsymptoms, and lung function.
Material and methods
Study population
Patients with noncystic fibrosis BQ in a stable phase of their illness(n = 80) were included in this prospective study from January 2005to February 2006. Sixty patients fulfilled EP3OS criteria (2) forCRS, 20 of whom with NP (9).
Design
The diagnosis of BQ was performed on the basis of characteristicclinical symptoms and chest-CT scanning (Siemens Emotion DuoTwo-slice 5 mm with high resolution slices 1 mm for pulmonaryparenchyma; Siemens, Munich, Germany). The stability of the BQcondition was assessed with a complete clinical evaluation, a forcedspirometry, and wherever necessary also with a thorax radiology.Stable BQ condition was defined as the absence of fever, no impair-ment of airflow limitation, no increase in sputum overproduction orchange in the macroscopic characteristics (purulence), and noincrease in chronic cough. In summary, no increase in respiratorysymptoms or modifications in the treatment over the previous6 weeks. The Ethics Committee of our institution approved the studyand signed informed consent was obtained from all the patients.Exclusion criteria were hospitalization in the previous 2 months,
use of antibiotics in the last 4 weeks, pseudomonas colonization, orpresence of a serious concomitant illness.To characterize the involvement of upper airway disease in
patients with BQ, the following diagnostic tools were used in thestudy: nasal symptom score, nasal endoscopy, sinonasal CT-scan(Siemens Somaton P4 Unislice 3 mm). Nasal congestion/obstruc-tion/blockage, reduction or loss of the sense of smell, anteriorrhinorrhea, postnasal drip, facial pain/pressure, itching, andsneezing were scored using the Rasp classification (0–3) (25). Polypsize was scored from 0 to 3 for each nasal cavity using nasalendoscopy, following Lildholdt�s classification (26). A radiologistblindly staged sinus occupation for each patient, using CT scanningand the Lund-MacKay score system (0–24) (27). All these resultshave been already published in a previous study (9).To characterize the involvement of lower airway disease, a chest
HRCT-scan was performed during the 3-month period prior to thesinonasal examination and the extent of BQ in each lobe wasgraded, using a scale from 0 to 3 (0, no involvement; 1, segmentinvolved; 2, more than one segment involved; and 3, gross cystic BQinvolving the entire lobe) (28).After a 4-week washout period for oral and intranasal steroids,
SNOT-20, SGRQ, and SF-36 questionnaires were completed by allpatients (29, 30).
Quality of life
1 The SNOT-20 comprises 20 items that assess symptoms ofCRS and the impact that they have on health status. Each itemis graded from 0 to 5. Higher scores represented a worseimpairment of health status because of upper airway symp-toms. A control group without CRS, studied to validate thequestionnaire, had a mean score of 0.6 (17).
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2 The SGRQ is a disease-specific instrument designed to measureimpact on overall health, daily life, and perceived well-being.The SGRQ was developed for use by patients with fixed andreversible airway obstruction, and has been widely used inCOPD, asthma and more recently in BQ research, including 56items (76 weighted responses) across three domains: symptoms(frequency and severity), activity (activities that cause or arelimited by breathlessness), and impact (SF, psychologicaldisturbances resulting from airways disease). Scores range from0 to 100, with higher scores indicating poorer QoL.
3 The Medical Outcomes Study SF-36 consists of 36 self-administered questions and was developed to measure eighthealth domains: physical functioning (PF), role physical, BP,general health (GH), vitality, role emotional (RE), SF, andmental health. Two summary scales are also included: thephysical component summary (PCS) and the mental compo-nent summary (MCS). We needed a generic questionnaire toassess QoL in pathology potentially involving both upper andlower airways: BQ and CRS (with or without NP). The Spanishversion of the SF-36 Health Survey was used (21). This versionis very similar to the original US questionnaire in absolutevalues, age, and gender. Scale scores in each domain andsummaries range from 0 to 100, higher scores indicating betterQoL (31). Data on SF-36 has already been published and willbe used here only to correlate with specific QoL questionnaires,and to support our objectives including a subgroup of patientswith BQ with no nasal pathology; given that only the PCS andthe MCS will be reported here.
Statistical analysis
Statistics were performed using spss for Windows (spss 11.0; SPSSInc., Chicago, IL, USA). All analyses were performed using two-tailed tests significance at the 0.05 level. The data are presented asmean ± SEM. All data were assessed for normal distribution andthe Bonferroni correction for multiple comparisons was used.Unpaired Student�s t-test was used to compare SNOT-20, SGRQ,and SF-36 of patients with BQ with and without CRS, and betweenpatients with or without NP. Pearson correlation coefficients wereused to examine the association between QoL scores (SNOT-20,SGRQ, SF-36) with nasal symptoms, and lung function.
Results
Demographic data
The mean age of BQ patients was 56.6 ± 1.8 years, 8%were smokers and 27% ex-smokers. No significantdifferences exist on the presence of CRS depending on
smoking history. Patients with CRS (81% female sub-jects) had a significantly higher female ratio (4.4 : 1), andthis was even higher in patients with CRS without NP(8.3 : 1), when compared with patients without CRS(1 : 1) (Table 1).
Quality of life
1 SNOT-20. Patients with CRS had significantly highertotal scores (2.1 ± 0.1; P < 0.001) than patientswithout CRS (0.4 ± 0.06) (Fig. 1). No significantdifferences were observed between patients with orwithout NP and depending on the BQ aetiology(idiopathic vs postinfectious).
2 SGRQ. Patients with CRS had significantly higherscores in total score (43.7 ± 2.2; P < 0.001), symp-toms (56.7 ± 3; P < 0.001), activities (41.6 ± 2.4;P < 0.001), and impact (33 ± 2.5; P < 0.001), thanpatients with no CRS (total: 24.7 ± 2.5; symptoms:35.9 ± 3.2; activities: 18.2 ± 3; impact: 19.9 ± 2.7)respectively (Fig. 1). No significant differences werefound between patients with or without NP or be-tween those with a different BQ aetiology (idiopathicvs postinfectious).
St George Respiratory Questionnaire total score (r =0.72; P < 0.01), symptoms (r = 0.56; P < 0.01), activ-ities (r = 0.72; P < 0.01), and impact (r = 0.64;P < 0.01) were correlated with the SNOT-20 totalscore.
3 SF-36. Patients with CRS had significantly lowerscores in PCS (64 ± 3.4; P < 0.05), and MCS(65.5 ± 4.7; P < 0.05) than patients with no CRS(PS: 76.2 ± 3.3; MS: 78.3 ± 5.3) respectively(Fig. 1). No significant differences were foundbetween patients with or without NP and dependingon the BQ aetiology (idiopathic vs postinfectious).
SF-36 PCS (r = )0.63; P < 0.01), and SF-36 MCS(r = )0.43; P < 0.01) correlated with SNOT-20 totalscore, while only PCS (r = )0.58; <0.05) correlated withSGRQ total score.
4 Correlation of QoL questionnaires (SNOT-20,SGRQ, SF-36) with nasal symptoms, lung function
Table 1. Epidemiologic characteristics of BQ patients included in the study
All BQ patients Non-CRS CRS CRS without NP CRS with NP
BQ, bronchiectasis; CRS, chronic rhinosinusitis; NP, nasal polyposis; M, male; F, female; FEV1, forced expiratory volume in 1 s.Unpaired Student�s t test: *P < 0.05, when compared with non-CRS patients; **P < 0.05, when compared with patients with CRS without NP.�Data presented as mean € SEM.
Guilemany et al.
1526 � 2009 John Wiley & Sons A/S Allergy 2009: 64: 1524–1529
(forced expiratory volume in 1 s; FEV1), and BQseverity (chest HRCT-scan).
(i) Nasal symptoms. Total nasal symptom scorecorrelated with SNOT-20 total score (r = 0.8;P < 0.01), SGRQ total score (r = 0.67;P < 0.01), as well as with the SF-36 PCS(r = )0.72; P < 0.01), and MCS (r = )0.48;P < 0.01).
(ii) Lung function. A mild but significant correla-tion was observed between FEV1 and SGRQtotal score (r = )0.41; P < 0.05), but notwith SGRQ total score and SF-36 componentsummaries.
(iii) Chest HRCT-scan. Patients with CRS(6.2 ± 0.5; P < 0.001) showed a higher BQseverity score than patients with no CRS(4.2 ± 0.7). No differences were observed be-tween patients with and without NP. Amild butsignificant correlation was observed betweenextension ofBQandSGRQ total score (r = 0.4;P < 0.05), but not with SNOT-20 total scoreand SF-36 component summaries.
Discussion
The main findings of our study were: (i) patients with BQand CRS had an impaired QoL when compared with BQ
patients with no CRS measured by SNOT-20, SGRQ,and SF-36; (ii) NP had no additional impact on QoL inpatients with BQs; (iii) upper airway QoL (SNOT-20)have been shown to correlate with both the lower airwaysQoL (SGRQ) and the GH QoL (SF-36). This studydemonstrates that CRS contributed to the impairment ofhealth status in patients with BQ.
The mean SNOT-20 score in patients with BQ whofulfill EP3OS criteria for CRS, with or without NP, was2.1. This was higher than the score registered in apopulation of patients with CRS, studied during thevalidation of the SNOT-20 questionnaire, who had amean score of 1.9 (17). Moreover, the SNOT-20 score inpatients with BQ without CRS (0.4) was similar to thatpreviously reported in normal control patients (0.6) (17).There were no differences between patients with CRSwith or without NP, although the SNOT-20 question-naire does not include sections on nasal congestion orsmell disorders. Although SNOT-22, which includes bothitems, could be more adequate for differentiating betweenCRS with NP and CRS without NP, this questionnairehas not yet been validated. The absence of a relationshipbetween current smoking status and the nasal or SNOT-20 scores is interesting as active smoking is known to beassociated with symptoms of CRS (32).
Quality of life measured by the SGRQ in patients withBQ assessing the pulmonary function and the presence ofcolonization (with pseudomonas or other microorganisms)
5SNOT-20 (total) SGRQ (total)
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Figure 1. Quality of life depending on the existence (CRS+, gray bars) or absence (CRS), white bars) of chronic rhinosinusitis,measured by SNOT-20, SGRQ, and SF-36 (MCS, PCS) questionnaires.
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has shown that patients with BQ colonized with pseudo-monas have worse pulmonary function and QoL thanuncolonized patients. Moreover, patients having microor-ganisms other than pseudomonas have a worse QoL thanthose without microorganisms (33). In our study, none ofthe patients with BQwere colonized by pseudomonas. Withrespect to the aetiology (idiopathic vs postinfectious), nodifferences in QoL were found in patients with BQ.Patients with NP have shown lower scores in all SF-36
domains except for PF and RE than patients withcoronary artery disease (34), COPD (22), and asthma(35). Nasal polyps are often an indicator of airway diseaseinvolving both the upper and lower respiratory tracts(36). Radenne et al. (37) have investigated the impact ofNP on QoL demonstrating that NPs impaired QoL in allSF-36 domains. Other studies have shown statisticallysignificant differences in seven of the eight domains of theSF-36, the exception being PF (12, 28, 38). More recentlyour group has demonstrated that asthma – but notaspirin sensitivity – has an additional negative impact onthe QoL of patients with NP (29).A previous study by our group demonstrated that
patients with BQ and CRS present a significantlyimpaired QoL when compared with the Spanish generalpopulation with no differences between CRS with NP andCRS without NP (24). In this study, patients with BQwith CRS showed an important negative impact on QoLwhen compared with patients with BQ without CRS, withno additional impact from the presence of NPs. Upperairway QoL (SNOT-20) have been shown to correlatewith both the lower airways QoL (SGRQ) and the GH
QoL (SF-36). This study provides additional evidencethat the degree of abnormality in nasal symptoms isassociated with the impairment of QoL in SNOT-20,SGRQ, and SF-36. Patients of the group CRS with NPhad a higher loss of sense of smell, without provoking anysignificant differences in QoL (SNOT-20, SGRQ, and SF-36), when compared with patients of the group CRSwithout NP. Otherwise, there was no significant correla-tion between the SNOT-20 and SGRQ total score(r = 0.21, P < 0.09), or between the SNOT-20 and theindividual impact, activity, or symptoms domains of theSGRQ in patients with upper airway symptoms andCOPD (39).
In conclusion, these results are the first to suggest thatCRS with and without NP have a considerable impact onthe QoL of patients with BQ. Hence, our data alsoconfirm that the �united airway� concept goes beyond thescope of asthma and COPD. In addition, treating thenose might also have beneficial effects on the health statusof patients with BQ.
Acknowledgments
Jose M. Guilemany has been supported by the National Plan forScientific Research, Development and Technologic Innovation ofthe Health�s Institute Carlos III – Health Research Fund (CM06/00071), and the Spanish Society of Oto-Rhino-Laryngology, Head& Neck Pathology. This study has been partially sponsored by theFundacio Catalana de Pneumologia (FUCAP).
2. Kaliner MA, Osguthorpe JD, FiremanP, Anon J, Georgitis J, Davis ML et al.Sinusitis: bench to bedside. Currentfindings, future directions. J Allergy ClinImmunol 1997;99:s829–s848.
3. Fokkens W, Lund V, Mullol J, Onbehalf of the European Position Paperon Rhinosinusitis and Nasal PolypsGroup. EP3OS 2007: European positionpaper on rhinosinusitis and nasal polyps2007. Rhinol Suppl 2007;20:1–136.
5. Ichimura K, Shimazaki Y, Ishibashi T,Higo R. Effect of new macrolide roxi-thromycin upon nasal polyps associatedwith chronic sinusitis. Auris NasusLarynx 1996;23:48–56.
9. Guilemany JM, Angrill J, Alobid I,Centellas S, Pujols L, Bartra J et al.United airways again: high pre-valence of rhinosinusitis and nasalpolyps in bronchiectasis. Allergy2009;64:790–797.
10. Polley L, Yaman N, Heaney L, CardwellC, Murtagh E, Ramsey J et al. Impactof cough across different chronic respi-ratory diseases: comparison of twocough-specific health-related quality oflife questionnaires. Chest 2008;134:295–302.
11. Jones PW, Quirk FH, Baveystock CM.Why quality of life measures should beused in the treatment of patients withrespiratory illness. Monaldi Arch ChestDis 1994;49:79–82.
12. Van Agthoven M, Fokkens WJ, van deMerwe JP, Marijke van Bolhuis E, Uyl-de Groot CA, Busschbach JJ. Quality oflife of patients with refractory chronicrhinosinusitis: effects of filgrastim treat-ment. Am J Rhinol 2001;15:231–237.
13. Gliklich RE, Metson R. The healthimpact of chronic sinusitis in patientsseeking otolaryngologic care. Otolaryn-gol Head Neck Surg 1995;113:104–109.
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14. Alobid I, Guilemany JM, Mullol J. Theimpact of chronic rhinosinusitis andnasal polyposis in quality of life. FrontBiosci 2009, in press.
15. Alobid I, Bernal-Sprekelsen M, MullolJ. Chronic rhinosinusitis and nasal pol-yps: the role of generic and specificquestionnaires on assessing its impact onpatient�s quality of life. Allergy2008;63:1267–1279.
16. Chan SL, Chan-Yeung MM, Ooi GC,Lam CL, Cheung TF, Lam WK et al.Validation of the Hong Kong Chineseversion of the St. George RespiratoryQuestionnaire in patients with bronchi-ectasis. Chest 2002;122:2030–2037.
17. Piccirillo JF, Merritt MG Jr, RichardsML. Psychometric and clinimetricvalidity of the 20-Item Sino-NasalOutcome Test (SNOT-20). OtolaryngolHead Neck Surg 2002;126:41–47.
18. Ragab SM, Lund VJ, Scadding G.Evaluation of the medical and surgicaltreatment of chronic rhinosinusitis: aprospective, randomised, controlledtrial. Laryngoscope 2004;114:923–930.
19. Hopkins C, Browne JP, Slack R, LundV, Topham J, Reeves B et al. The na-tional comparative audit of surgery fornasal polyposis and chronic rhinosinus-itis. Clin Otolaryngol 2006;31:390–398.
20. Hens G, Vanaudenaerde BM, BullensDM, Piessens M, Decramer M, DupontLJ et al. Sinonasal pathology in nonal-lergic asthma and COPD: �united airwaydisease� beyond the scope of allergy.Allergy 2008;63:261–267.
21. Alonso J, Regidor E, Barrio G, Prieto L,Rodriguez C, de la Fuente L. Popula-tion reference values of the Spanishversion of the Health QuestionnaireSF-36. Med Clin (Barc) 1998;111:410–416.
22. Alonso J, Prieto L, Ferrer M, Vilagut G,Broquetas JM, Roca J et al. Testing themeasurement properties of the Spanishversion of the SF-36 Health Surveyamong male patients with chronicobstructive pulmonary disease. Qualityof life in COPD study group. J ClinEpidemiol 1998;51:1087–1094.
23. Alonso J, Ferrer M, Gandek B, Ware JEJr, Aaronson NK, Mosconi P et al.Health-related quality of life associatedwith chronic conditions in eight coun-tries: results from the InternationalQuality of Life Assessment (IQOLA)Project. Qual Life Res 2004;13:283–298.
24. Guilemany JM, Alobid I, Angrill J,Ballesteros F, Bernal-Sprekelsen M,Picado C et al. The impact of bronchi-ectasis associated to sinonasal disease onquality of life. Respir Med2006;100:1997–2003.
25. Rasp G, Kramer MF, Ostertag P,Kastenbauer E. A new system for theclassification of ethmoid polyposis.Effect of combined local and systemicsteroid therapy. Laryngorhinootologie2000;79:266–272.
26. Lildholdt T, Rundcrantz H, LindqvistN. Efficacy of topical corticosteroidpowder for nasal polyps: a double-blind,placebo-controlled study of budesonide.Clin Otolaryngol 1995;20:26–30.
27. Lund VJ, MacKay IS. Staging inrhinosinusitus. Rhinology 1993;31:183–184.
28. Angrill J, Agusti C, de Celis R, Rano A,Gonzalez J, Sole T et al. Bacterial col-onisation in patients with bronchiecta-sis: microbiological pattern and riskfactors. Thorax 2002;57:15–19.
29. Alobid I, Benıtez P, Bernal-SprekelsenM, Guilemany JM, Picado C, Mullol J.The impact of asthma and aspirin sen-sitivity on quality of life of patients withnasal polyposis. Qual Life Res2005;14:789–793.
30. Alobid I, Benıtez P, Bernal M, Roca J,Alonso J, Picado C et al. Nasal polyp-osis and its impact on quality of life.Comparison between the effects ofmedical and surgical treatments. Allergy2005;60:452–458.
31. Ware JE, Konsinski M, Keller SD.SF-36 Physical and Mental HealthSummary Scales: a user�s manual.Boston, MA: The Health Institute, NewEngland Medical Center, 1994.
32. Benninger MS. The impact of cigarettesmoking and environmental tobaccosmoke on nasal and sinus disease: areview of the literature. Am J Rhinol1999;13:435–438.
33. Hernandez C, Abreu J, Jimenez A,Fernandez R, Martin C. Pulmonaryfunction and quality of life in relation tobronchial colonization in adults withbronchiectasis not caused by cysticfibrosis. Med Clin (Barc) 2002;118:130–134.
34. Failde I, Ramos I. Validity and reli-ability of the SF-36 health survey ques-tionnaire in patients with coronaryartery disease. J Clin Epidemiol2000;53:359–365.
35. Espinosa De Los Monteros MJ,Alonso J, Ancochea J, Gonzalez A.Quality of life in asthma: reliabilityand validity of the short form genericquestionnaire (SF-36) applied to thepopulation of asthmatics in a publichealth area. Arch Bronconeumol2002;38:4–9.
36. Johansson L, Bramerson A, HolmbergK, Melen I, Akerlund A, Bende M.Clinical relevance of nasal polyps inindividuals recruited from a generalpopulation-based study. Acta Otolar-yngol 2004;124:77–81.
37. Radenne F, Lamblin C, VandezandeLM, Tillie-Leblond I, Darras J, TonnelAB et al. Quality of life in nasal polyp-osis. J Allergy Clin Immunol1999;104:79–84.
38. Dur DG, Desrosiers MY, Dassa C.Quality of life in patients with rhinosi-nusitis. J Otolarymgol 1999;28:108–111.
39. Hurst JR, Wilkinson TM, DonaldsonGC, Wedzicha JA. Upper airwaysymptoms and quality of life in chronicobstructive pulmonary disease (COPD).Respir Med 2004;98:767–770.
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Bronconeumol 2006;42:135-40.
Introducción
En los últimos años se ha demostrado que enferme-dades que se suponía exclusivamente pulmonares obronquiales suelen asociarse a afección nasal y parana-sal. El concepto de rinobronquitis1 ha suscitado la ideade que las vías respiratorias superior e inferior constitu-yen una única vía, con una enfermedad común que afec-ta a todo el aparato respiratorio. Esto se ha demostrado yconfirmado en múltiples estudios epidemiológicos, conlo que ha aparecido el concepto de “una única vía, unaúnica enfermedad” (fig. 1). El ejemplo más claro de di-cha asociación es la rinitis y el asma2, pues se ha de-mostrado que ambas se dan de forma conjunta en la ma-yoría de los asmáticos y que el tratamiento de la rinitispuede tener efectos beneficiosos en el curso del asma3.
Las vías respiratorias superiores e inferiores tienencomo función común la de acondicionar y canalizar elaire del exterior al interior de los pulmones. Dentro deesta función común existen unas funciones especializa-das propias de las diferentes áreas que la forman: humi-dificación, calentamiento, filtración, fonación e inter-cambio gaseoso4.
Mucosas nasal y bronquial
Las mucosas nasal y bronquial tienen una estructurasimilar en el epitelio y la lámina propia. Una de las fun-
ciones más importantes de la nariz es actuar como ba-rrera para evitar la inhalación de sustancias nocivas tan-to infecciosas como de naturaleza no infecciosa. La na-riz actúa, además, como acondicionador del airerespirado calentándolo y humidificándolo. La funciónque más diferencia la nariz de las vías aéreas inferioreses sin duda la olfativa, que le es propia y tiene su baseen la pituitaria, situada en el techo de la fosa nasal5.
El epitelio escamoso que se encuentra en la válvulanasal se transforma en el resto de la nariz en un epiteliorespiratorio columnar ciliado seudoestratificado. En lanariz dicho epitelio columnar está formado por célulasciliadas, células no ciliadas, células basales, células ca-liciformes o goblet, y se diferencia del epitelio respira-torio bajo porque no existen células serosas, células deClara y células en cepillo6. La membrana basal estácompuesta por colágeno tipo IV, proteoglucanos, lami-nina y fibronectina. Debajo de ésta existe la denomina-da lamina reticularis, que se encuentra engrosada demanera difusa en los pacientes asmáticos7. Se observanengrosamientos focales de dicha membrana en los pa-cientes afectados de bronquiectasias, tuberculosis y ri-nosinusitis crónica8. En los pacientes con rinitis no sehan detectado cambios en esta zona9.
En la submucosa hay glándulas, vasos sanguíneos,nervios, células extravasculares y matriz extracelular.Una de las grandes diferencias se encuentran aquí, yaque el músculo liso se halla en la capa submucosa delbronquio, pero no en la submucosa de la nariz6.
En la nariz predominan las glándulas y los vasos.Aparte de los vasos arteriales, la vascularización nasalestá formada por lechos capilares, cortocircuitos arte-
Correspondencia: Dr. J.M. Guilemany.Servei d’ORL. Hospital Clínic.Villarroel, 170, esc. 8, pl. 2. 08015. Barcelona. España.Correo electrónico:[email protected]
Recibido: 15-3-2005; aceptado para su publicación: 5-4-2005.
Arch Bronconeumol. 2006;42(3):135-40 135
REVISIÓN
Relaciones entre rinosinusitis y bronquiectasias
J.M. Guilemanya, J. Mullola y C. Picadob
aUnitat de Rinologia. Servei d’ORL (ICEMEQ). Hospital Clínic. Universitat de Barcelona. Barcelona. España.bServei de Pneumologia (ICPCT). Hospital Clínic. Universitat de Barcelona. Barcelona. España.
La nariz y el bronquio presentan similitudes y diferenciastanto histológicas como funcionales. Son muchas las enfer-medades en que se asocian la afección nasosinusal y la bron-quial. La fibrosis quística, la discinesia ciliar primaria, elsíndrome de Young y el déficit de alfa-1-antitripsina son en-fermedades en las que se asocian bronquiectasias y rinosinu-sitis. En este artículo se realiza una revisión de las bron-quiectasias y de las enfermedades que las asocian junto aafección nasosinusal. El propósito es dar un nuevo enfoquede la patología nasosinusal observada en los pacientes afec-tados de bronquiectasias.
Relation Between Rhinosinusitis and Bronchiectasis
The nose and lungs have both histological and functionalsimilarities and differences. Sinonasal and bronchialinvolvement are associated in many diseases. Cystic fibrosis,primary ciliary dyskinesia, Young’s syndrome, and α-1antitrypsin deficiency are diseases in which bronchiectasisand rhinosinusitis are both present. This review considersthe diseases in which bronchiectasis occurs along withsinonasal manifestations. We propose examining sinonasaldisease from a new perspective by observing it in patientswith bronchiectasis.
Key words: Rhinitis. Sinusitis. Bronchiectasis.
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riovenosos, sinusoides y vasos venosos. Las venas quedrenan los sinusoides contienen músculo liso. Cuandodichas venas se contraen, se produce una expansión delos sinusoides, por lo que se incrementa el tamaño delos cornetes (tejido eréctil) y se refleja en los flujos na-sales. Esto no sucede en los bronquios, donde los cam-bios de resistencia al flujo se deben a la contracción dela musculatura lisa.
Transporte mucociliar
El aparato mucociliar está formado por los numero-sos cilios que emergen de la superficie de las célulasepiteliales columnares seudoestratificadas. Cada célulaciliada contiene alrededor de 200-300 cilios que reali-zan unas 500 batidas por minuto. La frecuencia de bati-das disminuye distalmente10, de modo que en las víasmedias la frecuencia es menor. Su alteración en estazona puede conducir al estancamiento de secreciones ypredisposición a padecer infecciones locales, lo que po-siblemente contribuya al desarrollo de bronquiectasiasen esa parte de las vías respiratorias11. El defecto en laultraestructura de los cilios, que altera y evita su normalmotilidad, predispone a las infecciones crónicas y recu-rrentes (rinosinusitis crónica), infecciones pulmonaresque provocan la aparición de bronquiectasias.
Aproximadamente, el 70-80% de los asmáticos pre-sentan rinitis y, según estudios recientes, la rinitis es unfactor que predispone al desarrollo ulterior de asma12.Este hecho ha llevado a la realización de estudios confinalidad preventiva dirigidos a tratar precozmente la ri-nitis para evitar el asma.
La poliposis nasal se detecta en el 2-4% de la pobla-ción, mientras que en los pacientes asmáticos la prevalen-cia llega al 7%. En quienes padecen asma leve es pocohabitual encontrar poliposis; a medida que aumenta lagravedad de la enfermedad, aparecen sinusopatía y poli-posis nasal con mucha mayor frecuencia, hasta el puntode que es excepcional que entre los pacientes con asma eintolerancia a la aspirina no se observe poliposis nasal13.
También se ha observado que existe relación entre laenfermedad pulmonar obstructiva crónica (EPOC) y la
rinitis14, pues en las biopsias de mucosa nasal de los in-dividuos con EPOC se han apreciado alteraciones infla-matorias similares a las halladas en las biopsias bron-quiales de estos mismos pacientes15.
La asociación de la rinorrea anterior y posterior, delos estornudos, de la congestión nasal y de la pérdidadel olfato con los síntomas respiratorios induce asimis-mo a pensar en la relación entre las vías respiratorias al-tas y bajas16.
Bronquiectasias
La bronquiectasia es la destrucción y dilatación anor-mal, permanente e irreversible de uno o más bronquiosmedianos y pequeños (de la cuarta a la novena genera-ción), producida, por destrucción de los componentesmusculares y elásticos de la pared bronquial. Se ignoracuál es su prevalencia en la población general y tampo-co se conoce bien la historia natural de la enfermedad,ya que no se han realizado estudios desde el inicio delproceso y con posterior análisis de su evolución17.
Laennec18 (1819) fue quien describió la bronquiecta-sia y señaló que se debía a la retención de secrecionesbronquiales con destrucción secundaria de la pared yposterior debilitamiento y dilatación de la misma. Estainterpretación es aún válida y se considera que la infla-mación bronquial desempeña un papel central. En 1922,con la introducción de la broncografía con contraste porSicard, se pudo observar con mejor precisión la imagende las bronquiectasias19.
Etiopatogenia
La bronquiectasia no es en sí misma una única en-fermedad, sino que puede ser el resultado de diversasenfermedades que lesionan la pared bronquial e inter-fieren así en sus defensas, ya sea de forma directa o in-directa. La afección puede ser difusa o local. Es típicala dilatación de los bronquios de tamaño medio, pero amenudo los bronquios pequeños también presentan en-grosamiento u obliteración. En las bronquiectasias seencuentran áreas de la pared bronquial destruidas e in-
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136 Arch Bronconeumol. 2006;42(3):135-40
Fig. 1. Rinosinusopatía crónica en laregión maxiloetmoidal bilateral (tomo-grafía axial computarizada de senos)junto a bronquiectasias bilaterales (to-mografía pulmonar) en un mismo pa-ciente.
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flamadas crónicamente; las células ciliadas están daña-das o destruidas y la producción de moco está aumen-tada, con lo que se pierde el tono normal de la pared.El aumento de la producción de moco facilita el creci-miento de las bacterias, obstruye los bronquios y favo-rece el estancamiento de las secreciones infectadas,con lesión posterior de la pared bronquial20. La infla-mación puede extenderse a los alveolos y producirbronconeumonía, formación de tejido cicatrizal y pér-dida del tejido pulmonar sano. Además, la inflamaciónde los vasos sanguíneos de la pared bronquial puedeocasionar expectoración hemoptoica o hemoptisis fran-ca. En el examen anatomopatológico se observan dila-taciones bronquiales, hipertrofia de la mucosa, en oca-siones con metaplasia escamosa, infiltrado linfocitariode la pared bronquial y desaparición de cartílago, mús-culo y fibras elásticas, que son sustituidas por tejido ci-catrizal21.
Las bronquiectasias localizadas suelen estar motiva-das por estenosis de algún bronquio debido a procesosinflamatorios, neoformativos o cuerpos extraños22.Cualquier circunstancia que produzca colapso por ab-sorción en la zona y fibrosis del tejido pulmonar adya-cente contribuye a la formación de bronquiectasias pordilatación compensadora del bronquio.
Las bronquiectasias difusas pueden deberse a múlti-ples causas (tabla I), entre las que destacan las enferme-dades congénitas que afectan a la función mucociliar,como son la fibrosis quística o las discinesias (síndromede Kartagener, síndrome de Young). En otras ocasionesse asocian a defectos en los mecanismos de defensa quefavorecen el desarrollo de infecciones bronquiales repe-tidas (inmunodeficiencia común variable, deficienciasde la formación de anticuerpos). Algunas bronquiecta-sias parecen haberse desarrollado a raíz de una bron-quiolitis infecciosa en la infancia (sarampión, virus res-piratorio sincitial). También pueden presentarse aso-ciadas a enfermedades sistémicas (artritis reumatoide,síndrome de Sjögren) o a enfermedades inflamatoriasintestinales (colitis ulcerosa, enfermedad de Crohn). Enun número reducido de casos pueden ser la consecuen-cia de la aspiración de sustancias tóxicas que lesionanlos bronquios.
Según su forma, existen 3 tipos de bronquiectasias:cilíndricas, varicosas y saculares (las 2 últimas suelenser las más graves clínicamente).
La biopsia de la mucosa bronquial revela la infiltra-ción por neutrófilos y linfocitos T21, además de un au-mento del contenido de elastasa en el esputo23 y un in-cremento de las concentraciones de interleucina 824,factor de necrosis tumoral alfa25 y prostanoides26.
La complicación más frecuente de las bronquiecta-sias es la sobreinfección27. La colonización más fre-cuente en estos pacientes es por Haemophilus influen-zae (55%) y Pseudomonas spp. (26%)28. Menosfrecuentes son el desarrollo de abscesos metastásicos depredomino en el sistema nervioso central (12-16%) ylas acumulaciones de amiloide tipo AA (6%). Otrascomplicaciones son la hipertensión pulmonar y el corpulmonale crónico. En las bronquiectasias saculares esmás frecuente encontrar los dedos en palillo de tambor.
Clínica
A pesar de que las bronquiectasias pueden producirsea cualquier edad, la enfermedad se inicia con mayor fre-cuencia en las primeras 2 décadas de la vida. Dado quelos síntomas pueden no manifestarse hasta mucho mástarde o incluso nunca, en algunas ocasiones se realiza eldiagnóstico radiológico cuando las bronquiectasias aúnson asintomáticas. La clínica más frecuente suele con-sistir en tos con expectoración abundante (broncorrea) yocasionalmente hemoptoica. La cantidad y el tipo de es-puto dependen de lo extensa que sea la enfermedad y dela presencia de una infección activa. En algunas ocasio-nes puede producirse hemoptisis masiva. Las neumo-nías son relativamente frecuentes y en algunos casos sepresentan de forma repetida. Las bronquiectasias exten-sas pueden llegar a ocasionar insuficiencia respiratoria,hipertensión pulmonar y cor pulmonale29.
Diagnóstico
El diagnóstico se realiza por historia clínica y radiolo-gía. La radiografía simple de tórax puede mostrar imá-genes muy indicativas de bronquiectasias como las de-nominadas en “raíl de tren”, quistes y bronquios rellenosde moco (imagen en dedos de guante), aunque lo másfrecuente es que sea normal o muestre cambios inespecí-ficos como el aumento de las marcas broncovasculares.Hoy día, la tomografía axial computarizada (TAC) de tó-rax permite diagnosticar la enfermedad con certeza altiempo que evalúa su localización y extensión30. Labroncografía, técnica usada en el diagnóstico antes de laintroducción de la TAC, ya no se utiliza.
El examen de la función pulmonar puede mostrar unpatrón obstructivo de grado diverso según la extensiónde la enfermedad, aunque no es infrecuente observar
GUILEMANY JM ET AL. RELACIONES ENTRE RINOSINUSITIS Y BRONQUIECTASIAS
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TABLA IEtiología de las bronquiectasias
Bronquiectasias localizadasObstrucción bronquial: aspiración de cuerpo extraño,
adenopatías, tumores pulmonares, tapón de moco
Bronquiectasias generalizadasCongénitas: discinesia ciliar primaria (síndrome de Kartagener),
fibrosis quística, deficiencia de alfa-1-antitripsina,traqueobroncomegalia (síndrome de Mounier-Kühn),deficiencia del cartílago (síndrome de Williams-Campbell),síndrome de Marfan, secuestro pulmonar
Postinfecciosa: viral (paramyxovirus, adenovirus,influenzavirus, virus de la inmunodeficiencia humana),bacteriana (Haemophilus, Pseudomonas, Klebsiella,Staphylococcus, Bordetella, Mycobacterium [M. tuberculosis]Mycoplasma [M. pneumoniae]), hongos (Aspergillus)
Alteraciones del sistema inmunitario: primaria(hipogammaglobulinemia, deficiencias del complemento),secundaria (leucemia linfocítica crónica, quimioterapia)
Tóxicos: inhalación de vapores tóxicos, aspiración de contenidogástrico
Otras: enfermedades inflamatorias intestinales (colitis ulcerosa,enfermedad de Crohn), síndrome de las uñas amarillas
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patrones mixtos ocasionados por la frecuente pérdida devolumen por colapso de algunos lóbulos asociada a laobstrucción. El intercambio de gases puede estar muyalterado debido a la presencia de zonas de cortocircuitoque causan en ocasiones hipoxemia acentuada31.
Tratamiento
El objetivo principal del tratamiento es controlar lasinfecciones y las secreciones, evitando la obstrucciónde las vías aéreas y sus complicaciones. Es fundamentalla fisioterapia respiratoria efectiva, con el fin de expul-sar las secreciones bronquiales. La disminución de al-gunas infecciones virales en la infancia gracias a la va-cunación ha permitido reducir el riesgo de desarrollarbronquiectasias. La vacunación contra el neumococo yHaemophilus y la vacunación anual contra el virus de lagripe contribuyen muy probablemente a disminuir elnúmero de episodios infecciosos graves32.
Enfermedades que ocasionan bronquiectasias y afección nasal asociada
Fibrosis quística
La fibrosis quística (FQ) es la alteración genética detipo autosómico recesivo más común en la poblacióncaucásica. Uno de cada 25 individuos es portador delgen33,34. Se calcula que afecta aproximadamente a unode cada 3.000-10.000 nacidos vivos por año. El gen res-ponsable de la FQ se encuentra en el locus simple delbrazo largo del cromosoma 7. La deleción de 3 pares debases o mutación delta F508 acontece aproximadamen-te en el 70% de todos los cromosomas de la FQ. La pro-teína defectuosa codificada por este gen anormal tieneuna estructura similar a la de una clase de proteínas co-nocidas por ser activas en el transporte epitelial y se hadenominado CFTR (cystic fibrosis transmembrane re-gulator)35. Esta proteína defectuosa contribuye al malfuncionamiento de los canales del cloro, lo cual provocaun aumento de la viscosidad del moco que dificulta sueliminación y favorece la colonización por Staphylococ-cus aureus y Pseudomonas mucoide.
Se han identificado muchas otras mutaciones cercadel locus afectado. Los pacientes con FQ se caracteri-zan por presentar infecciones repetidas en el tracto res-piratorio, insuficiencia pancreática exocrina e infertili-dad. En estadios tempranos la radiografía de tórax36
muestra afectación de los lóbulos superiores, que sevuelven difusos con la progresión de la enfermedad. Lafunción pulmonar puede ser normal o presentar un pa-trón de tipo obstructivo o mixto. En la presentaciónadulta de la enfermedad, los síntomas normalmente hanestado presentes durante años, pero muchas veces no setienen en cuenta al ser moderados. El adulto puede pre-sentar bronquiectasias, rinosinusitis, insuficiencia pan-creática, pancreatitis aguda, colelitiasis e infertilidad.La obstrucción nasal es el síntoma más frecuente entrelos pacientes con FQ. La incidencia de poliposis nasales de más del 20% de los pacientes. Hay diferentes pa-trones de rinosinusitis: pólipos nasales, rinosinusitiscrónica purulenta y mucopiosinusitis del antro del seno
maxilar con protrusión de la pared nasal lateral37. Estaúltima entidad recibe el nombre de seudomucocele ma-xilar. En el diagnóstico de la FQ es importante la prue-ba del sudor38 (las concentraciones de sodio o cloro sonde 60 mmol/l, mientras que en individuos sanos y porta-dores del gen de la FQ son de 30 mmol/l), el estudio ge-notípico y la TAC pulmonar y sinusal. Los objetivos deltratamiento son: reducir la obstrucción, controlar las in-fecciones39, disminuir la inflamación y mejorar el esta-do nutricional. El tratamiento nasal consiste en lavadoscon suero fisiológico, corticoterapia intranasal, antibio-terapia y, en caso necesario, cirugía endoscópica funcio-nal de senos.
Discinesia ciliar primaria
La discinesia ciliar primaria (DCP) es una enferme-dad congénita en la que existe una alteración total oparcial de la función de las células ciliadas40. Es una en-fermedad autosómica recesiva que afecta a uno de cada16.000 nacidos vivos y se presenta clínicamente con ri-nosinusitis, bronquiectasias y, de forma menos frecuen-te, esterilidad en los varones. En el síndrome de discine-sia (dificultad para el movimiento) ciliar primariaexisten alteraciones estructurales o funcionales en losmicrotúbulos de los cilios que son responsables del mo-vimiento de éstos. Tales alteraciones originan un malaclaramiento del moco de los cilios, con las consiguien-tes infecciones bronquiales supurativas y bronquiecta-sias. Se alteran todas las estructuras donde existen cilios: epitelios de las vías respiratorias, senos paranasa-les, trompa de Eustaquio y espermatozoides (astenos-permia)41.
El 50% de los individuos afectados presenta síndro-me de Kartagener, que se caracteriza por la tríada debronquiectasias, rinosinusitis crónica y situs inversus(dextrocardia)42,43. La rinitis con presencia de rinorreaanterior se encuentra en todos los enfermos afectadosde DCP, y en algunos casos se acompañan de póliposnasales y disminución o pérdida completa del olfato. Enla TAC de senos es típico observar ocupación de los se-nos etmoidales y maxilares, junto a hipoplasia del senofrontal. El diagnóstico se realiza mediante una combi-nación de pruebas, como son: tiempo de sacarina, óxidonítrico nasal, biopsia nasal, en la que se observa la fre-cuencia de batida de los cilios y la densidad de éstosmediante microscopia electrónica44. En el tratamientodel paciente con DCP resulta de gran importancia la fi-sioterapia respiratoria con drenaje postural y la antibio-terapia en las agudizaciones por infecciones respirato-rias. La realización de polipectomía endoscópica o decirugía endoscópica funcional de senos es beneficiosaen los pacientes con rinosinusitis crónica rebelde al tra-tamiento.
El diagnóstico se establece por el estudio ultraestruc-tural de muestras obtenidas de la mucosa nasal, en lasque se suele observar la ausencia de los brazos de la di-neína o la disposición anómala de los microtúbulos. Es-tudios recientes han demostrado concentraciones bajasde óxido nítrico nasal en los pacientes afectados de di-cha enfermedad45.
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Síndrome de Young
El síndrome de Young se caracteriza por la tríada:bronquiectasias, rinosinusitis crónica e infertilidad. Enlos pacientes que lo presentan la actividad ciliar es nor-mal y el moco, muy viscoso. La biopsia nasal bajo mi-croscopia electrónica no muestra cambios en la estruc-tura de los cilios46. La azoospermia causante de lainfertilidad se debe a la obstrucción del epidídimo, yaque la espermiogénesis es totalmente normal. El diag-nóstico se basa en la clínica (enfermedad sinopulmonarcrónica, azoospermia), así como en la exclusión de FQy de síndromes de inmovilidad ciliar47.
Deficiencia de alfa-1-antitripsina
La alfa-1-antitripsina es una glucoproteína producidapor los hepatocitos, cuya función es inhibir las protea-sas (elastasa), en particular las liberadas por los neutró-filos, en su misión reparadora y de limpieza de agentesexternos en el pulmón. Al inhabilitar las proteasas, evitala destrucción de tejidos sanos en el organismo48. El genque la codifica está situado en el cromosoma 14. El dé-ficit pulmonar de alfa-1-antitripsina produce enfisemapor la destrucción progresiva de los alveolos en la terce-ra y cuarta décadas de la vida. El humo del tabaco con-tribuye a la destrucción pulmonar, ya que aumenta laactividad de la elastasa, disminuye la actividad de laalfa-1-antitripsina por su oxidación e inactiva la síntesisde elastina, lo que interfiere en la reparación pulmonar;por lo tanto, dejar de fumar debe ser la principal priori-dad del paciente diagnosticado de déficit de alfa-1-anti-tripsina49.
El enfisema producido por el déficit de alfa-1-anti-tripsina es paracinar, con destrucción de todo el ácino.Se localiza frecuentemente en las bases y existe un au-mento de la distensibilidad (compliance) pulmonar. Ladisminución de las concentraciones de alfa-1-antitripsi-na produce un desequilibrio entre esta proteína (antipro-teasa) y la elastasa (proteasa). Al no existir suficientecantidad de alfa-1-antitripsina, las elastasas siguen des-truyendo progresivamente la elastina de las paredes al-veolares50. Se consideran valores normales de proteínaalfa-1-antitripsina en sangre los comprendidos en el in-tervalo de 150 a 350 mg/dl o 20-53 µM. Con concentra-ciones inferiores a 80 mg/dl u 11 µM existe el riesgo depadecer alguna de las enfermedades relacionadas con sudéficit51. El segundo órgano más afectado es el hígado,afectando más frecuentemente a recién nacidos y niños.Los pacientes afectados presentan historia previa de dé-ficit de alfa-1-antitripsina o de enfermedad pulmonar.En el pulmón se observan enfisema, bronquitis crónica,bronquiectasias, asma de difícil tratamiento y neumo-nías de repetición. Se recomienda realizar medicionescuantitativas de alfa-1-antitripsina en los siguientes ca-sos: enfisema precoz, antecedentes familiares, disnea otos en varios miembros de una misma familia o diferen-tes generaciones, adultos con bronquiectasias sin etiolo-gía evidente, pacientes con enfermedad obstructiva pul-monar, enfermedad hepática de causa desconocida,pacientes asmáticos que no responden a tratamiento yen la paniculitis inexplicable52. La rinitis alérgica y las
rinosinusitis de repetición también constituyen una ma-nifestación frecuente en estos pacientes incluso en au-sencia de enfermedad obstructiva pulmonar53.
Conclusiones
De acuerdo con el concepto de “una única vía, unasola enfermedad”, los pacientes afectados de bronquiec-tasias presentan en muchos casos afectación nasosinu-sal. Se desconoce la frecuencia de esta asociación, yaque no se ha realizado un estudio sistemático de afecta-ción nasosinusal en pacientes con bronquiectasias. Nose sabe, por ejemplo, si los gérmenes que colonizan lasvías inferiores son los responsables del proceso nasal.Tampoco se ha investigado si las características de larespuesta inflamatoria de las vías bajas son similares alas nasales y sinusales. Dada la mejor accesibilidad dela nariz en la realización de exploraciones (endoscopia,biopsia, recogida de secreciones nasales) en compara-ción con las vías inferiores (fibrobroncoscopia), el con-trol evolutivo de la enfermedad pulmonar podría mejo-rar y ser menos invasivo. Se ha demostrado que eltratamiento de la rinitis alérgica y la poliposis nasal me-jora la evolución del paciente con asma, pero se desco-noce si algo similar puede ocurrir entre la sinusitis y lasbronquiectasias. La demostración de la presencia de unproceso infeccioso e inflamatorio similar de las vías aé-reas superiores e inferiores de los pacientes con bron-quiectasias permitirá realizar estudios encaminados aaclarar los mecanismos responsables de su origen.
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Tesis Doctoral III. Trabajo Experimental
149
Cartas al Editor 1. "Una vía respiratoria unificada": las bronquiectasias
también se asocian a rinosinusitis crónica y pólipos nasales. Arch
Bronconeumol 2009 (en prensa). DOI:10.1016/j.arbres.2009.03.006
ARTICLE IN PRESS
Arch Bronconeumol. ]]]];](]):]]]–]]]
0300-28
doi:10.1
Comrinos
www.archbronconeumol.org
Carta al Director
Una vıa respiratoria unificada: las bronquiectasias tambien seasocian a rinosinusitis cronica y polipos nasales
A United Airway: Bronchiectasis Is Also Associated With ChronicRhinosinusitis and Nasal Polyps
Sr. Director:
En noviembre de 2008, ARCHIVOS DE BRONCONEUMOLOGIA publico lanormativa de la Sociedad Espanola de Neumologıa y CirugıaToracica (SEPAR) sobre el diagnostico y tratamiento de lasbronquiectasias1. Aunque de enorme importancia para el diag-nostico y tratamiento de las bronquiectasias, el documento nomenciona en absoluto el impacto que dicha enfermedad tiene enla vıa respiratoria superior en forma de rinosinusitis cronica con ysin polipos nasales, hecho que ya se habıa puntualizado en unartıculo de revision publicado en esta Revista en 20062.
El concepto de ‘‘una vıa unica’’ se ha demostrado mediante laasociacion epidemiologica, fisiopatologica, de diagnostico ytratamiento de la enfermedad broncopulmonar con la nasosinu-sal: asma con rinitis alergica3, asma con poliposis nasal4, asma noalergica y enfermedad pulmonar obstructiva cronica con rinosi-nusitis cronica5. La experiencia clınica en los Servicios deOtorrinolaringologıa y Neumologıa del Hospital Clınic de Barce-lona ha llevado a investigar desde hace varios anos la asociacionde enfermedad nasosinusal en pacientes con bronquiectasias.
Como fruto de esta investigacion, contamos hoy dıa con 2artıculos publicados6,7 y uno actualmente en prensa sobre laasociacion de bronquiectasias y rinosinusitis cronica con o sinpoliposis nasal. Entre sus conclusiones, debemos destacar que 3de cada 4 (77%) pacientes con bronquiectasias reunen criteriosclınicos y radiologicos de rinosinusitis cronica, mientras uno decada 4 (25%) presenta polipos nasales en la endoscopia nasal7.Dichos resultados apoyan el concepto de ‘‘una unica vıa aerea’’ eindican que en las llamadas bronquiectasias postinfecciosaspodrıa haber algun proceso todavıa desconocido que afectara atoda la vıa aerea. Ademas, los pacientes con bronquiectasias yrinosinusitis cronica tienen una peor calidad de vida, medidatanto con cuestionarios genericos como especıficos, que losafectados de bronquiectasias sin sinusopatıa cronica6.
De estos resultados se puede concluir que los pacientes conbronquiectasias deberıan evaluarse siempre, tanto clınicamentocomo mediante endoscopia nasal y/o tomografıa computarizada
96/$ - see front matter & 2009 SEPAR. Publicado por Elsevier Espana, S.L. Todo
016/j.arbres.2009.03.006
o citar este artıculo: Guilemany Toste JM, et al. Una vıa resinusitis cronica y polipos nasales. Arch Bronconeumol. 2009. d
nasosinusal, a fin de diagnosticar una posible rinosinusitis cronica,con o sin polipos nasales. Ası pues, a todos los pacientes conbronquiectasias, ademas de aquellos con asma y enfermedadpulmonar obstructiva cronica, se les deberıa realizar un estudiootorrinolaringologico, idealmente en unidades multidisciplinarias,con el objetivo de mejorar su diagnostico, tratamiento yseguimiento tanto de la enfermedad broncopulmonar como dela nasosinusal.
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Josep Maria Guilemany Toste a,b,c, Cesar Picado Valles b,c,d yJoaquim Mullol i Miret a,b,c,�
aUnitat de Rinologia i Clınica de l’Olfacte, Servei d’Otorrino-
laringologia, Hospital Clınic, Barcelona, EspanabCentro de Investigacion Biomedica en Red de Enfermedades
Respiratorias (CibeRes)cImmunoal � lergia Respiratoria Clınica i Experimental, IDIBAPS,
Barcelona, EspanadServei de Pneumologia i Al � lergia Respiratoria, Institut Clınic del
Torax, Hospital Clınic, Barcelona, Espana
�Autor para correspondencia.Correo electronico: [email protected] (J. Mullol i Miret)
s los derechos reservados.
piratoria unificada: las bronquiectasias tambien se asocian aoi:10.1016/j.arbres.2009.03.006