Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

The Role of Respiratory Viruses in Exacerbations of Cystic Fibrosis in Adults

31 de mayo de 2012 actualizado por: Manchester University NHS Foundation Trust

The Role of Respiratory Viruses in Exacerbations of Cystic Fibrosis in Adults.

Respiratory viruses, such as those that cause colds and influenza, are very common in the general population. The average adult will experience between 2 and 4 viral respiratory illnesses each year. It is known that respiratory viruses can cause flare-ups of chronic lung diseases such as asthma and chronic obstructive pulmonary disease. In children with CF, respiratory viral infections have been identified in nearly half of all exacerbations and are associated with a decline in lung function and increased frequency of hospital admission and acquisition of new bacterial pathogens.

Currently, little is known about the impact of viral infections on the course of CF lung disease in adults and no large-scale prospective studies in this area have been performed to date. It is unknown how often respiratory viruses can be found in patients with CF when they are well and what consequences they have on the course of exacerbations of CF lung disease. This study will identify the frequency of common viral infections in adults with CF and determine the effects they have on lung function, the rate and diversity of bacterial infection and patients' treatment burden. The information gained from this study will lead to improved prevention and treatment of respiratory infections in CF.

Descripción general del estudio

Estado

Terminado

Condiciones

Descripción detallada

Background Lung disease in cystic fibrosis (CF) is characterized by chronic airway infection with periodic exacerbations which are associated with impaired lung function, reduced quality of life and increased healthcare costs.1 2 Respiratory viruses are common and are known to be associated with exacerbations of other chronic respiratory diseases such as asthma.3 Studies in children with CF have shown that respiratory viruses are common during exacerbations. Wat and colleages identified respiratory viruses in 46% of patients at the time of pulmonary exacerbation of CF.4 Several older studies in children with CF have found an association between viral infections and decline in lung function, frequency and duration of hospital admission and CF disease progression.5-7 An association between respiratory viruses and acquisition of Pseudomonas aeruginosa has been proposed but this remains unproven.8 Retrospective data in adults has shown an incidence of viral infection in pulmonary exacerbations of between 8.7 and 45.8%.9 10 To date, no prospective studies have been conducted to investigate the impact of these infections on clinical outcomes in adults with CF, or the effects of these infections on respiratory bacterial flora. It is entirely unknown how frequently viruses can be identified in adults with CF when they are asymptomatic. This study will fill these gaps in current knowledge and improve our management of respiratory infections in CF.

Primary Research Question What is the prevalence of respiratory virus infection in adults with CF during a pulmonary exacerbation and when clinically stable?

Secondary Research Questions

  1. What is the effect of respiratory virus infection on lung function and disease progression?
  2. What is the effect of respiratory virus infection on bacterial and fungal colonization in CF?
  3. What is the effect of respiratory virus infection on the CF microbiome, specifically the rate and diversity of bacterial infection?
  4. Are any specific rhinovirus sub-types (including rhinovirus C) associated with worse outcome following viral respiratory infections in adults with CF?

Methodology This is a prospective observational study looking at the incidence and consequences of respiratory virus infection in CF both during exacerbations and during periods of clinical stability. Subjects eligible for the study will be all patients with CF over the age of 18 years attending the Manchester Adult Cystic Fibrosis Centre (MACFC). We aim to recruit 100 patients into the study. Participants will be screened for respiratory viruses at baseline and every two months throughout a twelve month follow-up period. Screening will also occur at the time of diagnosis of a pulmonary exacerbation or onset of new respiratory symptoms. At each visit an oral mouth wash, sputum sample and a nose-swab will be taken; the mouth wash and an aliquot of sputum will be stored frozen for later microbial diversity analysis. On each occasion, sputum will also be sent for conventional bacteriology/mycology to identify any new bacterial or fungal colonization.

Respiratory viruses in the sputum will then be identified using the polymerase chain reaction (PCR) technique. The following viruses will be tested for: adenovirus, human metapneumovirus, influenza A, B & C (including influenza A H1N1), parainfluenza 1-3, respiratory syncytial virus and rhinovirus. Rhinovirus identifications will be sequenced to determine the frequency of infection with individual subtypes.

After 6 months of the study, 10 CF individuals who provided a stable and viral-linked exacerbation samples will be selected and the total bacterial diversity in their sputum examined by state-of-the-art, cultivation independent 16S rRNA pyrosequencing analysis.11 To account for the potential of oral flora contamination in the sputum samples, the mouth wash taken prior to each sputum sample will also be examined. Total DNA will be extracted from the selected samples and the V1-3 region of the 16S rRNA gene amplified using tagged primers specifically developed for pyrosequencing sequence analysis. The derived bacterial 16S rRNA gene sequences (8000-10,000 reads per sample) will be trimmed to 450 bases and compared to the Ribosomal Database Project (RDP; http://rdp.cme.msu.edu) to determine the identity of the bacteria from which the DNA derived. Correlation between viral-linked exacerbation and the load of known pathogens (eg. Pseudomonas aeruginosa), new players (CF anaerobes), and the total/unique bacterial flora in the sputum will be made.

Data Analysis & Statistical Methods The primary outcome measure will be identification of a respiratory virus in nose/throat swab or sputum. Statistical analysis will use longitudinal regression modeling of the cohort which takes account of the repeated sampling of each patient. The study will have over 80% power to detect differences of 20% (e.g. 50% vs. 30%) in incidence of viral infection between exacerbation and routine sample periods in patients showing at least one-third of the samples with infection (using a McNemar's paired test with p=0.05).

Ethical Approval The study has been reviewed by the North West 9 Research Ethics Committee - Greater Manchester West and has received a favourable opinion.

References

  1. Goss C et al. Exacerbations in cystic fibrosis. 1: Epidemiology and pathogenesis. Thorax 2007;62:360-7.
  2. Britto M et al. Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis. Chest 2002;121:64-72.
  3. Johnston S et al. The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am J Respir Crit Care Med 1996;154:654-60.
  4. Wat D et al. The role of respiratory viruses in cystic fibrosis. J Cystic Fibros 2008;7:320-8.
  5. Smyth A et al. Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis. Arch Dis Child 1995;73:117-20.
  6. Wang E et al. Association of respiratory viral infections with pulmonary deterioration in patients with cystic fibrosis. N Engl J Med 1984;311:1653-8.
  7. Collinson J et al. Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 1996;51:1115-22.
  8. Petersen NT et al. Respiratory infections in cystic fibrosis patients caused by virus, chlamydia and mycoplasma--possible synergism with Pseudomonas aeruginosa. Acta Paed Scand 1981;70:623-8.
  9. De Schutter I et al. Detection of viruses in pulmonary exacerbations in CF. J Cystic Fibros, 2010:s37.
  10. Naseer R et al. Pulmonary exacerbations in adult patients with cystic fibrosis associated with positive viral PCR. J Cystic Fibros 2010;9:S37.

11 White J et al. Culture-independent analysis of bacterial fuel contamination provides insights into the level of concordance with conventional cultivation. Appl Environ Microbiol (in review) 2010.

Tipo de estudio

De observación

Inscripción (Actual)

100

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Lancashire
      • Manchester, Lancashire, Reino Unido, M23 9LT
        • University Hospital of South Manchester NHS Foundation Trust

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra no probabilística

Población de estudio

Adults with cystic fibrosis attending the Manchester Adult Cystic Fibrosis Centre, Manchester, UK

Descripción

Inclusion Criteria:

  • Patients with cystic fibrosis attending Manchester Adult CF Centre
  • Age ≥18 years
  • Capable of providing written informed consent
  • Able and willing to provide required samples and meet visit schedule

Exclusion Criteria:

  • Previous lung transplantation

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Identification of respiratory viruses in sputum, nose- or throat-swabs
Periodo de tiempo: 12 months
A panel of 6 viruses will be tested for using polymerase chain reaction (PCR)technology: adenovirus, rhinovirus, metapneumovirus, parainfluenza virus 1-3, influenza A,B&C and respiratory syncytial virus
12 months

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Investigador principal: William G Flight, MBChB, University Hospital of South Manchester NHS FoundationTrust

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de diciembre de 2010

Finalización primaria (Actual)

1 de abril de 2012

Finalización del estudio (Actual)

1 de abril de 2012

Fechas de registro del estudio

Enviado por primera vez

9 de noviembre de 2010

Primero enviado que cumplió con los criterios de control de calidad

9 de noviembre de 2010

Publicado por primera vez (Estimar)

10 de noviembre de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

1 de junio de 2012

Última actualización enviada que cumplió con los criterios de control de calidad

31 de mayo de 2012

Última verificación

1 de mayo de 2012

Más información

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Ensayos clínicos sobre Fibrosis quística

3
Suscribir