Acute exposure to fine ambient particulate matter and pulmonary exacerbations in cystic fibrosis: A case-crossover study

In cystic fibrosis (CF) lung disease, increased exposure to PM 2.5 (particulate matter < 2.5 μm in diameter) has been linked to more frequent pulmonary exacerbations, yet the timing of exposure that presents the greatest exacerbation risk remains uncertain. Our study investigated whether short-term increases in ambient fine particulate matter (PM 2.5 ) contribute to exacerbation risk in individuals with CF. We analyzed data from 108 participants across 17 U.S. clinical sites enrolled in the Early Intervention in Cystic Fibrosis Exacerbation study (October 2011 – July 2015), who recorded forced expiratory volume in 1 second (FEV 1 ) measurements at least twice weekly. Exacerbation cases were identified via the FEV 1 indicated exacerbation signal (FIES), defined as a ≥ 10% predicted decline in FEV 1 . Daily 24-hour average PM 2.5 concentrations were estimated at the residential ZIP code using a high-resolution spatiotemporal exposure model. A time-stratified case-crossover design modeled exacerbation onset and PM 2.5 exposure, controlled for temperature, relative humidity, and holiday impacts. We analyzed 6936 FEV 1 observations yielding 1432 exacerbation cases, averaging 7.7 cases per person-year, matched to 4794 control dates in the same year, month, and day of the week. Increased exacerbation risk occurred one (OR: 1.18; 95% CI: 1.02–1.36), two (OR: 1.20; 95% CI: 1.04–1.40), and three (OR: 1.23; 95% CI: 1.05–1.43) days after PM 2.5 exposure, but not on the day of onset (OR: 1.07; 95% CI: 0.92–1.25). Integrating home-monitored lung function with hyperlocal exposure estimates provides improved temporal resolution for detecting acute environmental triggers and may inform early intervention strategies in CF care. e-ICE clinical trial registered with www.clinicaltrials.gov (NCT01104402) • Daily home spirometry enabled precise identification of pulmonary exacerbation onset, revealing substantially more events than traditional clinical-based definitions. • Short-term increases in ambient PM 2.5 were significantly associated with higher exacerbation risk, with strongest effects observed 1-3 days after exposure rather than on the same day of onset. • A time-stratified case-crossover design effectively isolated acute ambient pollution effects, while controlling for long-term trends, seasonality, temperature, relative humidity, holiday impacts in CF care, and time-invariant individual characteristics. • High-resolution spatiotemporal PM 2.5 estimates at the residential ZIP code level improved exposure assessment, allowing detection of lagged environmental triggers that coarser models may miss. • Findings suggest that pulmonary exacerbations may be predictable responses to short-term environmental stressors, supporting the development of early intervention tools that integrate home lung-function monitoring with real-time air quality data.