Long-term particulate matter exposure and accelerated respiratory malignant transformation: A multi-state trajectory from initial injury to lung cancer.

While particulate matter (PM) exposure is an established risk factor for non-cancerous lung diseases and lung cancer morbidity/mortality, the extent of the association between long-term PM exposure and respiratory malignant transformation remains poorly characterized. Using a 7-year, nationwide cohort of 2.7 million Chinese adults, this study employed a weighted multi-state model to trace disease progression from baseline (no lung diseases) through non-cancerous lung diseases to lung cancer incidence and mortality. Our analysis showed that each 10 μg/m3 rise in 3-year fine particulate matter (PM2.5) concentration correlated with increased risks of respiratory disease progression: 3.4 % higher risk of baseline-to-non-cancerous lung disease transition (HR=1.034, 95 % CI: 1.030-1.038); 4.9 % higher risk of non-cancerous lung disease-to-lung cancer progression (HR=1.049, 95 % CI: 1.027-1.073); and 21.1 % higher post-diagnosis mortality risk (HR=1.211, 95 % CI: 1.161-1.262). PM2.5 exposure was linked to elevated direct mortality risks, with 9.7 % and 13.96 % increases noted in baseline-to-death and non-cancerous lung disease-to-death transitions, respectively (HR=1.097, 95 % CI: 1.089-1.105; HR=1.139, 95 % CI: 1.124-1.155). Inhalable particulate matter (PM10) showed comparable correlational patterns. Stratified analyses identified demographic disparities: Females and urban residents exhibited greater susceptibility to PM-associated transition from baseline to non-cancerous lung disease, whereas males and rural populations showed stronger associations with PM-linked respiratory disease-to-death transition risks. These findings underscore the imperative for coordinated primary (pollution control), secondary (early screening), and tertiary (cancer survivorship) prevention strategies targeting exposure-level-specific vulnerabilities.