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Abstract and Introduction
Abstract
Background Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symptoms are not well described.
Objectives Study goals were to compare molecular detection of viruses from concurrent upper airway and sputum samples in children with CF and to describe relative frequency of respiratory viral infections and identify potential clinical associations.
Methods We conducted a 2-year prospective surveillance study in 44 children with CF aged 6–18 years. Upper airway and sputum samples were collected quarterly and during pulmonary exacerbations and tested for respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types 1–4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses. Physical exams and symptom surveys were used to identify respiratory signs and symptoms.
Results Upper airway samples were collected at 359 visits; concordance of PCR-based viral detection was examined in a subset of paired upper airway and sputum samples from 21 participants at 92 visits. Rhinovirus was the most commonly detected virus (23·1% overall), and rhinovirus detection was the same for both sample types (21·7% each). Sensitivity and specificity for the detection of rhinovirus in sputum relative to upper airway sampling were 70% and 91·7%, respectively. Respiratory symptoms associated with rhinovirus detection included increased cough, increased nasal congestion, increased sputum production, and wheezing.
Conclusions A relatively high frequency of rhinovirus detection was observed by either upper airway or sputum samples, and clinical findings suggest a significant-associated symptom burden.
Introduction
Prior to the use of molecular detection methods to detect respiratory viruses, detection rates of respiratory viruses in clinical specimens from children with cystic fibrosis (CF) were remarkably low. Viral detection in this patient population was complicated by multiple factors, including tenacious respiratory specimens that inhibited viral growth in cell culture, bacterial and fungal overgrowth contaminating respiratory specimens, and the general problems with cultivation of difficult-to-propagate respiratory viruses such as rhinovirus, coronavirus, and other viral pathogens. The use of potentially insensitive serologic assays further hampered the detection of respiratory viral infections in this patient population. None-the-less, the association of respiratory viral infections with exacerbations of lung disease and overall progression of CF airway disease has been appreciated for a number of years.
Molecular diagnostic techniques circumvent the problems associated with viral culture in children with CF and permit the detection of viruses that are extremely difficult or impossible to culture even in optimal settings. Multiple viruses, including influenza, parainfluenza, adenovirus, and respiratory syncytial virus (RSV), have been clearly associated with pulmonary exacerbations and worsening lung function in children with CF. However, clinical symptoms associated with new respiratory viruses such as coronavirus and human metapneumovirus are not well described, and the symptomatic impact of rhinovirus, the most commonly detected virus in CF patients, is not clear. Although respiratory viruses have been detected in both upper and lower airway samples, previous studies in patients with CF have not directly compared detection of respiratory viruses in upper airway and sputum samples.
We performed a 2-year prospective cohort study in school-age children with CF to compare respiratory virus detection in upper airway and sputum samples. Real-time polymerase chain reaction (PCR) for the detection of respiratory viruses was performed on respiratory specimens collected during routine clinic visits and during pulmonary exacerbation. Paired upper airway and sputum samples were collected on a subset of participants within the larger cohort study, and the concordance of PCR-based viral detection between sample types was determined. The association between the detection of respiratory viruses and clinical symptoms was also evaluated.
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