학술논문
Estudio de la función de los cilios mediante imagen digital de alta velocidad. comparación con la ultraestructura ciliar en la discinesia ciliar primaria
Document Type
Dissertation/Thesis
Author
Source
TDX (Tesis Doctorals en Xarxa)
Subject
Language
Spanish; Castilian
Abstract
Introducción La discinesia ciliar primaria (DCP) es una enfermedad rara (1:15.000 recién nacidos) caracterizada por una alteración en la estructura y función ciliar que impide el correcto aclaramiento de las secreciones respiratorias. Sus manifestaciones clínicas incluyen tos productiva, rinitis crónica, otitis de repetición, bronquitis recurrentes, bronquiectasias, infertilidad masculina, subfertilidad femenina y situs inversus (50%) o heterotaxia (6-12%). El diagnóstico se basaba inicialmente en la detección de las alteraciones estructurales mediante la microscopía electrónica. Se han desarrollado nuevos métodos diagnósticos que contribuyen a facilitar su diagnóstico, aunque éste sigue siendo difícil de realizar. Objetivos Valorar la utilidad diagnóstica del estudio de motilidad ciliar comparado con el estudio de la ultraestructura ciliar con microscopía electrónica. Establecer valores de normalidad del estudio de motilidad ciliar. Describir las características de un grupo de pacientes afectos de discinesia ciliar primaria. Valorar la utilidad de las pruebas de despistaje de esta enfermedad: cuestionario de síntomas PICADAR y óxido nítrico nasal en este grupo de pacientes y en una muestra ampliada. Métodos Selección de una muestra de población normal para establecer valores de referencia del estudio de motilidad ciliar. Realización del estudio de motilidad ciliar en una muestra de pacientes con sospecha de discinesia ciliar estudiados previamente mediante microscopía electrónica y comparación de ambas técnicas. Valorar la utilidad como pruebas de despistaje del cuestionario de síntomas PICADAR y del óxido nítrico nasal en esta muestra de pacientes y en una muestra ampliada. Resultados Los valores de normalidad del estudio de motilidad ciliar fueron: frecuencia del batido 9,94 Hz (8,56-11,32), índice de discinesia 12,10% (2,54-21,66) e índice de inmovilidad 0,13% (0-1,51). Las características clínicas más importantes que definieron al grupo de pacientes con discinesia ciliar primaria fueron: padecer distrés respiratorio neonatal y presentar tos y rinorrea desde el primer día de vida. La mayoría de los pacientes con situs inversus estaban en este grupo. También presentaban más frecuencia de tos continua productiva, rinorrea persistente, mayor porcentaje de sordera y de sensación de oídos tapados que el resto de los grupos. En el grupo de pacientes estudiados con microscopía electrónica su sensibilidad y especificidad fue del 90,9% y 48,3% y la del estudio de motilidad ciliar del 100% y 80%. En este grupo, la sensibilidad y especificidad del cuestionario PICADAR fue del 90,9% y 86,7% (con un punto de corte > 4 puntos), y la del óxido nítrico nasal del 80% y 100% (con un punto de corte en 220 ppb o 72,5 nL/min). En la muestra ampliada de pacientes, la sensibilidad y especificidad del estudio de motilidad ciliar fue del 100% y 82,8%, la del cuestionario PICADAR del 92,9% y 71,7% (con un punto de corte > 3 puntos) y la de la medida del óxido nítrico nasal del 91,9% y 97,5% (con un punto de corte en 248 ppb o 87,9 nL/min). Conclusiones El estudio de la motilidad ciliar (frecuencia y patrón de batido) mediante videomicroscopía óptica tuvo una mejor sensibilidad y sobretodo una mejor especificidad que el estudio de la ultraestructura con microscopía electrónica para el diagnóstico de discinesia ciliar primaria. La escala predictiva PICADAR y la determinación de óxido nítrico nasal son buenas pruebas de despistaje de la discinesia ciliar primaria, lo que se ha confirmado tanto en la muestra inicial como en la muestra ampliada de pacientes.
Introduction Primary ciliary dyskinesia (PCD) is a rare disease (1:15,000 newborns) characterized by an alteration in the ciliary structure and function that prevents the correct clearance of respiratory secretions. Its clinical manifestations include productive cough, chronic rhinitis, recurrent otitis, recurrent bronchitis, bronchiectasis, male infertility, female subfertility, and situs inversus (50%) or heterotaxia (6-12%). Some years ago, the diagnosis was based on the structural alterations detected by electron microscopy. New diagnostic methods have been developed to contribute its diagnosis, although it remains difficult to perform. Objectives To assess the diagnostic utility of the ciliary motility study compared with the study of the ciliary ultrastructure by electron microscopy. Establish normality values of the ciliary motility study. Describe the characteristics of a group of patients with primary ciliary dyskinesia. To assess the usefulness of screening tests for this disease: the PICADAR symptom questionnaire and nasal nitric oxide in this group of patients and in an extended sample. Methods Selection of a healthy population sample to establish reference values for the ciliary motility study. Ciliary motility study was performed in a sample of patients with suspected ciliary dyskinesia previously studied by electron microscopy and comparison of both techniques. To assess the usefulness of the PICADAR symptom questionnaire and nasal nitric oxide as screening tests in this sample of patients and in an extended sample. Results The normal values of the ciliary motility study were beat frequency 9.94 Hz (8.56-11.32), dyskinesia index 12.10% (2.54-21.66) and immotility index 0,13% (0-1.51). The most important clinical characteristics that defined the group of patients with primary ciliary dyskinesia were neonatal respiratory distress and presenting cough and rhinorrhea from the first day of life. Most of the patients with situs inversus were in this group. They also had a higher frequency of continuous productive cough, persistent rhinorrhea, a higher percentage of deafness and a sensation of blocked ears than the rest of the groups. In the group of patients studied by electron microscopy, its sensitivity and specificity were 90.9% and 48.3% and for the ciliary motility study was 100% and 80%. In this group, the sensitivity and specificity of the PICADAR questionnaire was 90.9% and 86.7% (with a cut-off point > 4 points), and for the nasal nitric oxide was 80% and 100% (with a point of cut-off at 220 ppb or 72.5 nL/min). For the expanded sample of patients, the sensitivity and specificity of the ciliary motility study was 100% and 82.8%, for the PICADAR questionnaire 92.9% and 71.7% (with a cut-off point > 3 points) and for the nasal nitric oxide measurement 91.9% and 97.5% (with a cut-off point of 248 ppb or 87.9 nL/min). Conclusions The study of ciliary motility (frequency and beat pattern) performed by high-speed videomicroscopy had better sensitivity and a better specificity than the study of the ultrastructure performed by electron microscopy for the diagnosis of primary ciliary dyskinesia. The PICADAR predictive questionnaire and the nasal nitric oxide determination are good screening tests for primary ciliary dyskinesia, which has been confirmed both in the initial sample and in the expanded sample of patients.
Introduction Primary ciliary dyskinesia (PCD) is a rare disease (1:15,000 newborns) characterized by an alteration in the ciliary structure and function that prevents the correct clearance of respiratory secretions. Its clinical manifestations include productive cough, chronic rhinitis, recurrent otitis, recurrent bronchitis, bronchiectasis, male infertility, female subfertility, and situs inversus (50%) or heterotaxia (6-12%). Some years ago, the diagnosis was based on the structural alterations detected by electron microscopy. New diagnostic methods have been developed to contribute its diagnosis, although it remains difficult to perform. Objectives To assess the diagnostic utility of the ciliary motility study compared with the study of the ciliary ultrastructure by electron microscopy. Establish normality values of the ciliary motility study. Describe the characteristics of a group of patients with primary ciliary dyskinesia. To assess the usefulness of screening tests for this disease: the PICADAR symptom questionnaire and nasal nitric oxide in this group of patients and in an extended sample. Methods Selection of a healthy population sample to establish reference values for the ciliary motility study. Ciliary motility study was performed in a sample of patients with suspected ciliary dyskinesia previously studied by electron microscopy and comparison of both techniques. To assess the usefulness of the PICADAR symptom questionnaire and nasal nitric oxide as screening tests in this sample of patients and in an extended sample. Results The normal values of the ciliary motility study were beat frequency 9.94 Hz (8.56-11.32), dyskinesia index 12.10% (2.54-21.66) and immotility index 0,13% (0-1.51). The most important clinical characteristics that defined the group of patients with primary ciliary dyskinesia were neonatal respiratory distress and presenting cough and rhinorrhea from the first day of life. Most of the patients with situs inversus were in this group. They also had a higher frequency of continuous productive cough, persistent rhinorrhea, a higher percentage of deafness and a sensation of blocked ears than the rest of the groups. In the group of patients studied by electron microscopy, its sensitivity and specificity were 90.9% and 48.3% and for the ciliary motility study was 100% and 80%. In this group, the sensitivity and specificity of the PICADAR questionnaire was 90.9% and 86.7% (with a cut-off point > 4 points), and for the nasal nitric oxide was 80% and 100% (with a point of cut-off at 220 ppb or 72.5 nL/min). For the expanded sample of patients, the sensitivity and specificity of the ciliary motility study was 100% and 82.8%, for the PICADAR questionnaire 92.9% and 71.7% (with a cut-off point > 3 points) and for the nasal nitric oxide measurement 91.9% and 97.5% (with a cut-off point of 248 ppb or 87.9 nL/min). Conclusions The study of ciliary motility (frequency and beat pattern) performed by high-speed videomicroscopy had better sensitivity and a better specificity than the study of the ultrastructure performed by electron microscopy for the diagnosis of primary ciliary dyskinesia. The PICADAR predictive questionnaire and the nasal nitric oxide determination are good screening tests for primary ciliary dyskinesia, which has been confirmed both in the initial sample and in the expanded sample of patients.