Physical activity attenuated risk of idiopathic pulmonary fibrosis: a prospective cohort study

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Although physical activity (PA) may influence inflammation and oxidative stress, which are implicated in IPF pathogenesis, evidence regarding its association with incident IPF remains limited. In this prospective cohort study, we included 87,738 participants from the UK Biobank with valid accelerometer-based PA data and no IPF at baseline. PA intensity was categorized as sedentary, light, or moderate-to-vigorous. Polygenic risk scores (PRS) were derived from 13 genome-wide significant variants for genetic risk stratification analyses. Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident IPF. Over the follow-up period, 386 participants developed IPF. Moderate-to-vigorous physical activity (MVPA) was associated with a lower risk of incident IPF (HR: 0.90; 95% CI: 0.85–0.94; p < 0.001). The inverse association remained consistent across different levels of genetic susceptibility, although effect estimates were smaller among participants with higher genetic risk. Sensitivity analyses supported the robustness of the findings. MVPA was associated with a lower risk of incident IPF across different levels of genetic susceptibility. These findings suggest that physical activity may represent a modifiable lifestyle factor associated with IPF risk and warrant further investigation in future mechanistic and intervention studies. Not applicable.