Urinary polycyclic aromatic hydrocarbon metabolites, Club cell secretory protein and lung function

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with lung function decline. However, the underlying mechanisms for the association remain unclear.

To explore potential role of a lung epithelial biomarker, Club cell secretory protein (CC16), in associations between PAH exposures and lung function decline.

We investigated 3384 adults from the Wuhan-Zhuhai cohort, and followed up at three years after first examination. Linear mixed models was used to quantify dose-response relationships between urinary monohydroxylated PAH metabolites (OH-PAHs) and lung function, as well as OH-PAHs and plasma CC16. Mediation analysis was conducted to investigate role of CC16 in the association between OH-PAHs and lung function. We also estimated the relationships between OH-PAHs and lung function change in three years among participants with different levels of CC16.

Each 1-unit increase of log-transformed total urinary high and low molecular weight OH-PAHs (∑HMW OH-PAH and ∑LMW OH-PAHs) were associated with a 22.59 and 25.25ml reduction of FEV₁ respectively, while∑HMW OH-PAH was associated with a 30.38ml reduction of FVC. Moreover, these negative associations between OH-PAHs and lung function levels were significant only among low CC16 group (<15.83ng/ml). CC16 concentration decreased monotonically with increased high molecular weight OH-PAHs (∑HMW OH-PAHs) when ∑HMW OH-PAH concentration was over 0.67μg/mmol Cr. CC16 mediated 22.13% of the association between ∑HMW OH-PAH and FVC among individuals with higher ∑HMW OH-PAH. After three years of follow-up, subjects with low level of plasma CC16 had a significant decline of FVC when exposed to high level of ∑HMW OH-PAH.

CC16 play an important role in the association between high molecular weight PAHs and FVC. Individuals with low plasma CC16 level might suffer a decline in lung function when exposed to high level of high molecular weight PAHs.