Fine Particulate Matter Exposure and Cystic Fibrosis Morbidity in the Age of CFTR Modulators, an Observational Study.

RATIONALE:Despite CFTR modulators transforming cystic fibrosis (CF) care, patients still show wide variability in pulmonary outcomes. The contribution of ambient fine particulate matter (PM2.5) exposure to this variability in the modulator era is unknown. OBJECTIVES:To quantify the effects of PM2.5 on pulmonary outcomes in people with CF and to assess whether CFTR modulator use modifies these effects. METHODS:In a retrospective cohort of 5,661 from the Cystic Fibrosis Foundation Registry, ZIP codes were linked to daily PM2.5. Long-term exposure was defined as the fraction of days ≥ 12 µg/m3 from birth to spirometry. Linear mixed-effects models assessed lung function, negative binomial regression estimated exacerbation counts, and Cox proportional hazards models evaluated time to pathogen acquisition. Interaction terms tested modification by CFTR modulator use. RESULTS:Each 10 percentage-point increase fraction of long-term days ≥ 12 µg/m3 (range 0% to 88%) was associated with an 0.82-point decrease in precent predicted FEV1 (95% CI -1.07 to -0.56; P < .0001) and a 0.97-point decrease in FVC % predicted (95% CI -1.20 to -0.73; P < .0001). Similarly, pulmonary exacerbation rates increased by 6.7% (95% CI 2.55-11.1; P = .0014). Higher PM2.5 also predicted earlier P. aeruginosa and MRSA positivity. CFTR modulators significantly attenuated PM2.5-related decrements in lung function but no significant interactions regarding pulmonary exacerbations were identified. CONCLUSIONS:Long-term PM2.5 exposure remains a strong predictor of lung function, pulmonary exacerbations, and bacterial pathogen acquisition. While CFTR modulators appeared to mitigate the association between PM2.5 exposure and lung function, no such mitigation was identified in relationship to pulmonary exacerbations.