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

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 s (FEV₁) measurements at least twice weekly. Exacerbation cases were identified via the FEV₁ indicated exacerbation signal (FIES), defined as a ≥10 % predicted decline in FEV₁. Daily 24-h 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 FEV₁ 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 clinicaltrials.gov/ (NCT01104402).