(568) The association between antifungal use and lung function in people with cystic fibrosis and Aspergillus positive cultures

Background: Aspergillus fumigatus (Af) positive cultures are common in people with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis (ABPA) is known to contribute to respiratory symptoms and FEV1 decline in CF. Yet, the clinical significance of the Af positive cultures outside of ABPA is unknown and Aspergillus airways infection, commonly known as Aspergillus bronchitis, has yet to be clearly defined. Furthermore, it is unclear whether antifungal therapy for Aspergillus airways infection improves clinical outcomes in CF. We aimed to determine the clinical effectiveness of antifungal therapy in people with CF with Aspergillus species isolation CF in the United States.

Methods: We conducted a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry from January 1, 2005 to December 31, 2019. The study population included people with CF age 6 years and older without history of solid organ transplantation with at least one positive Aspergillus culture. Index date for each subject was the date of first Aspergillus positive culture. The primary exposure was antifungal use (yes/no). The primary outcome was FEV₁ percent predicted (FEV1pp). We fit a linear mixed-effects regression model with marginal structural models using inverse probability of treatment weighting (IPTW) to control for confounders. Demographic, treatment, clinical and microbiologic covariates were included in the IPTW model based on the known clinical associations with disease severity. Antifungal use and clinical covariates were treated as time-varying.

Results: A total of 16,050 of subjects had at least one positive Aspergillus culture. Median age at index date was 17.8 years [12.0, 26.5]. Additional characteristics at index date included, 48.9% female sex, 87% non-Hispanic white, 89% with pancreatic insufficiency, baseline FEV1 percent predicted of 99% [77,112], Pseudomonas aeruginosa positive culture in 46.4%. Antifungal use was present in 833 (5.2%) in the index year of first Aspergillus positive culture. Antifungal use was associated with a 4.8 lower FEV1pp compared to usual care (no antifungal use), ß -4.83 (95% CI -5.19, -4.47).

Conclusions: Antifungal use was associated with lower FEV1pp compared to usual care without antifungal use for people with CF with known Aspergillus positive cultures. This may be explained by residual unmeasured confounding not addressed by the IPTW model. Randomized controlled trials of antifungal therapy for treatment for Aspergillus airways infection are needed to determine its clinical efficacy in this population.

Acknowledgements: This work was supported by the National Institutes of Health (K23HL146970).

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