Long-term carbon disulfide exposure impairs pulmonary function in urban adults: Prevention insights from genetic susceptibility and lifestyle improvement in a repeated-measured cohort

Efforts on interactions of carbon disulfide (CS 2 ) exposure, genetic susceptibility, and lifestyle on pulmonary function that are critical to prevention are lacking. Urinary CS 2 metabolite (2-thiothiazolidine-4-carboxylic acid, TTCA) and pulmonary function parameters for 4409 observations from 2025 individuals were measured at baseline and two follow-ups in the Wuhan-Zhuhai cohort. The polygenic risk score (PRS) was derived from 1020 pulmonary function-associated genetic variants, and the healthy lifestyle score (HLS) was comprehensively constructed using life habits including smoking, drinking, physical exercise, and diet status. Linear mixed-effects models with interaction plots were employed to estimate the independent and interaction effects of TTCA, PRS, and HLS on pulmonary function. Elevated urinary TTCA, elevated PRS, and decreased HLS were significantly associated with reduced ratio of forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) and peak expiratory flow (PEF) (all P < 0.05). Notably, the estimated adverse effect of urinary TTCA on PEF interactively became more pronounced with increasing PRS or/and decreasing HLS ( P interaction < 0.05). Particularly, the most substantial effects of urinary TTCA on PEF were observed in participants with high PRS and low HLS in both cross-sectional and longitudinal analyses, with the estimated effects of −90.56 mL/s (95% confidence interval: −146.66, −34.71) for continuous TTCA cross-sectionally and − 406.31 mL/s (−746.61, −64.63) for persistently high TTCA longitudinally. Our findings highlight that reducing CS 2 exposure and improving lifestyle, particularly in individuals with higher genetic susceptibility to pulmonary function decline, may help in the early prevention of pulmonary injury from CS 2 exposure. • CS 2 exposure can impair pulmonary function in the general population. • Elevated PRS and decreased HLS are associated with pulmonary function decline. • CS 2 exposure, PRS, and HLS exhibit interactions on pulmonary function decline. • Reducing CS 2 and improving lifestyle in high PRS subjects are urgent to implement.