The Clinical Association between Aspergillus fumigatus and Respiratory Outcomes in Adolescents and Adults with Cystic Fibrosis

Rationale: The clinical significance of Aspergillus fumigatus (Af) detection in the absence of allergic bronchopulmonary aspergillosis in cystic fibrosis (CF) airways remains unclear. Yet, some clinicians initiate antifungal therapy for Af-positive respiratory cultures out of concern for infection in people with CF. Objectives: To determine the association between the presence of Af and respiratory outcomes in individuals with CF. Methods: We conducted a prospective longitudinal cohort study of 206 adults and adolescents (age 14 yr and older) with CF and collected sputum for selective fungus culture. We assessed clinical outcome measurements, including patient-reported outcomes (measured by the Cystic Fibrosis Questionnaire–Revised), spirometry, and number of pulmonary exacerbations (PEx) for a 1-year period. We used mixed-effects linear models to determine the association between positive Af culture results, defined as Af detection in sputum culture at the study visit, with both respiratory domain score and forced expiratory volume in 1 second (FEV₁) percent predicted, adjusted for confounders. Mixed-effects Poisson regression models were employed to examine the association between positive Af culture results and PEx events. We explored the association between Af history, defined as Af detection at baseline or within 2 years of enrollment, and respiratory outcomes. Results: Af prevalence was 10.3% (95% confidence interval [CI], 6.8, 15.7) at baseline. Forty-eight (23.3%; 95% CI, 17.7, 29.7) participants had at least one Af-positive culture result during the study period. Positive Af culture result was not associated with lower respiratory domain score. However, Af history was associated with a 6.48-point lower respiratory domain score, reflective of worse respiratory quality of life (95% CI, 211.96, 20.99; P = 0.02). Positive Af culture result was associated with a 2.54% lower FEV₁ percent predicted (95% CI, 24.64, 20.44; P = 0.02) and a 1.71-fold increase in severe PEx incidence (95% CI, 1.05, 2.76; P = 0.03). Conclusions: Positive Af culture result was not associated with lower patient-reported, respiratory-related quality of life. Yet, positive Af culture result was associated with both lower FEV₁ percent predicted and increased frequency of severe PEx warranting intravenous antibiotics in adolescents and adults with CF. Future studies are required to better understand the direct role of Af in lung disease progression in CF.