Effect of Club cell secretory proteins on the association of tobacco smoke and PAH co-exposure with lung function decline: A longitudinal observation of Chinese coke oven workers

Exposure to polycyclic aromatic hydrocarbons (PAH) and tobacco smoke is associated with epithelial damage and reduced lung function. Club cell secretory protein (CC16) is a known biomarker for lung epithelial cells. However, the potential relationships between PAH and tobacco smoke exposure, CC16 levels, and reduced lung function remain unclear.This longitudinal study aimed to explore the potential role of CC16 in the association of tobacco smoke and PAH co-exposure with lung function.We enrolled 313 workers from a coking plant in China in 2014 and followed them up in 2019. The concentrations of PAH and nicotine metabolites in urine were determined using high-performance liquid chromatography (HPLC) with a fluorescence detector and HPLC-tandem mass spectrometry, respectively. The plasma CC16 concentration was determined using an enzyme-linked immunosorbent assay.An analysis of the generalized estimating equation showed that each 1-unit increase in log-transformation of the last tertile of trans-3'-hydroxycotinine (3HC) was associated with a 3.30 ng/ml decrease in CC16. Restricted cubic spline analysis revealed a significant nonlinear dose-effect association between cotinine (COT) and CC16 (Pnonlinear = 0.018). In the low- CC16 subgroup, we found a significant association between total nicotine metabolites and forced vital capacity (FVC%) (β: 1.45, 95% CI: 2.87, -0.03), and the associations of nicotine (NIC), COT, and 3HC with FVC% were all of marginal significance. High levels of total hydroxyl polycyclic aromatic hydrocarbons (ΣOH-PAH) and NIC in the urine had an interactive effect on the decline of CC16 (P < 0.05). Cross-lagged panel analysis indicated that the decrease in CC16 preceded the decrease in FVC%. CC16 mediated the association between elevated nicotine metabolites and decreased FVC% in the low- CC16 subgroup.CC16 plays an essential role in the association of PAH and tobacco smoke exposure with reduced lung function. Coke oven workers with low plasma CC16 levels are more likely to experience decreased lung function after tobacco smoke exposure.