Comprehensive evaluation of serum cotinine on human health: Novel evidence for the systemic toxicity of tobacco smoke in the US general population

Accumulating epidemiological studies have demonstrated that smoking caused damage to human health. However, these studies almost focused on the individual smoking pattern rather than the toxic ingredients of tobacco smoke. Despite the exact accuracy of cotinine as a smoking exposure biomarker, there were few studies investigating the association between serum cotinine and human health. This study aimed to provide novel evidence about the harmful effect of smoking on systemic health from the perspective of serum cotinine. All used data was acquired from 9 survey cycles (2003−2020) of the National Health and Nutrition Examination Survey (NHANES) program. The mortality information of participants was derived from the National Death Index (NDI) website. The disease status of participants, including respiratory, cardiovascular, and musculoskeletal diseases, was obtained from questionnaire surveys. The metabolism-related index, including obesity, bone mineral density (BMD), and serum uric acid (SUA), was obtained from examination data. Multiple regression methods, smooth curve fitting, and threshold effect models were used for association analyses. With a total of 53,837 subjects included, we detected an L-shaped association between serum cotinine and obesity-related index, a negative association between serum cotinine and BMD, a positive association between serum cotinine and nephrolith and coronary heart disease (CHD), a threshold effect of serum cotinine on hyperuricemia (HUA), osteoarthritis (OA), chronic obstructive pulmonary disease (COPD), and stroke, as well as a positive saturate effect of serum cotinine on asthma, rheumatoid arthritis (RA), all-cause, cardiovascular disease (CVD)-cause, cancer-cause, and diabetes-cause mortality. In this study, we investigated the association between serum cotinine and multiple health outcomes, indicating the systematic toxicity of smoking exposure. These findings provided novel epidemiological evidence about how passive exposure to tobacco smoke affects the health condition of the general US population.