Associations between biomarkers of nicotine/tobacco exposure and respiratory symptoms among adults who exclusively smoke cigarettes in the U.S. Findings from the PATH Study Waves 1–4 (2013–2017)

Significance: Determining if tobacco-related biomarkers of exposure (BOE) are associated with respiratory symptoms is an important public health tool that can be used to evaluate the potential harm of different tobacco products. Methods: Adult data from people who exclusively smoked cigarettes (N = 2,438) in Waves 1–4 (2013–2017) of the Population Assessment of Tobacco and Health Study were stacked to examine associations between baseline and follow-up within wave pairs (W1-W2, W2-W3, W3-W4). Weighted generalized estimating equation models were used to evaluate associations between biomarkers of nicotine, tobacco-specific nitrosamines, acrolein, acrylonitrile, cadmium, and lead at baseline/follow-up and respiratory symptom(s) (wheezing/whistling in the chest, wheezing during exercise, and/or dry cough in the past 12 months) at follow-up. Results: Higher acrolein metabolite (CEMA) levels at follow-up were associated with increased odds of respiratory symptoms at follow-up for people who exclusively smoked cigarettes (aOR = 1.34; 95% CI = 1.06, 1.70), including when limited to those without a diagnosed respiratory disease (aOR = 1.46; 95% CI = 1.12, 1.90) and those who smoked daily (aOR = 1.40; 95% CI = 1.06, 1.84). Higher cadmium levels at baseline (while controlling for follow-up levels) were associated with reduced odds of respiratory symptoms at follow-up (aOR = 0.80; 95% CI = 0.65, 0.98) among people who exclusively smoked cigarettes without a respiratory disease. There were no significant associations between baseline/follow-up BOE and follow-up respiratory symptoms for people who smoked cigarettes non-daily. Conclusions: This research supports measuring biomarkers of acrolein, such as CEMA, as a potential intermediate measurement for increased respiratory symptom development. Measuring these biomarkers could help alleviate the clinical burden of respiratory disease.