Local and systemic inflammation may mediate diesel engine exhaust induced lung function impairment in a Chinese occupational cohort.

Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in ambient air impairs lung function. The objectives were to assess the contribution of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and interleukin-6 [IL-6]) inflammation to DEinduced lung function impairment using a unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127), made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase in CRP were identified in DETs compared with non-DETs (all p values < 10(-4)), which were further corroborated by showing a dose-response relationship with internal dose for DE exposure (all p values <. 04) and a time-course relationship with DE exposure history (all p values <. 005). Mediation analysis showed that 43% of the difference in FEV1 between DETs and non-DETs can be explained by circulating CC16 and CRP (permuted p<. 001). An inverse dose-dependent relationship between FeNO and internal dose for cigarette smoke was identified (p =.0003). A range of 95% lower bounds of benchmark dose of 1.0261-1.4513 mu g phenanthrols/g creatinine in urine as an internal dose was recommended for regulatory risk assessment. Local and systemic inflammation may be key processes that contribute to the subsequent development of obstructive lung disease in DE-exposed populations.