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

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.