Prevalence and Clinical Impact of Respiratory Viral Infections from the STOP2 Study of Cystic Fibrosis Pulmonary Exacerbations.

RATIONALE:Rates of viral respiratory infection (VRI) are similar in people with cystic fibrosis (CF) and the general population; however, the associations between VRI and CF pulmonary exacerbations (PEx) require further elucidation. OBJECTIVES:To determine VRI prevalence during CF PEx and evaluate associations between VRI, clinical presentation, and treatment response. METHODS:The Standardized Treatment of Pulmonary Exacerbations II (STOP2) study was a multicenter, randomized trial to evaluate different durations of intravenous antibiotic therapy for PEx. In this ancillary study, participant sputum samples from up to three study visits were tested for respiratory viruses using multiplex PCR. Baselines and treatment associated changes in mean lung function (percent predicted forced expiratory volume in one second; ppFEV1), respiratory symptoms (Chronic Respiratory Infection Symptom Score; CRISS), weight, and C-reactive protein (CRP) were compared as a function of virus detection. Odds of PEx retreatment within 30 days and future PEx hazard were modeled by logistic and Cox proportional hazards regression, respectively. RESULTS:A total of 1,254 sputum samples from 621 study participants were analyzed. One or more respiratory viruses were detected in sputum samples from 245 participants (39.5%). Virus-positive participants were more likely to be receiving CF transmembrane conductance regulator (CFTR) modulator therapy (45% vs. 34%) and/or chronic azithromycin therapy (54% vs. 44%), and more likely to have received treatment for nontuberculous mycobacterium infection in the preceding two years (7% vs. 3%). At study visit 1, virus-positive participants were more symptomatic (mean CRISS score 53.8 vs. 51.1), had evidence of greater systemic inflammation (log10CRP concentration: 1.32 log10 mg/L vs. 1.23 log10 mg/L), and had a greater drop in ppFEV1 from the prior 6-month baseline (5.8 vs 3.6). Virus positivity was associated with reduced risk of future PEx (HR: 0.82, 95% CI: 0.69-0.99; p=0.034) and longer median time to next PEx (255 days vs. 172 days, p=0.021) compared to virus-negativity. CONCLUSIONS:Over one-third of STOP2 participants treated for a PEx tested positive for a respiratory virus with more symptomatic initial presentation compared to virus-negative participants, but favorable long-term outcomes. More refined phenotyping of PEx, taking VRIs into account, may aid in optimizing personalized management of PEx. CLINICAL TRIAL REGISTRATION:NCT02781610 Primary Source of Funding: Cystic Fibrosis Foundation.