Decreased cigarette smoking may partially explain the increased prevalence of antinuclear antibodies in the United States

Gregg Dinse¹Clarice R Weinberg²Christine Gibson Parks²Caroll A Co¹Jessica T Priest¹Edward K.L. Chan³Frederick William Miller^2,4*

• ¹Public Health & Scientific Research, DLH, LLC, Bethesda, MD, United States
• ²Division of Intramural Research, National Institute of Environmental Health Sciences (NIH), Durham, United States
• ³University of Florida, Gainesville, Florida, United States
• ⁴National Institutes of Health (NIH), Bethesda, Maryland, United States

Introduction: Despite well-known harmful health effects of smoking, research supports an inverse association with some autoimmune diseases. High-titer antinuclear antibodies (ANA) are associated with autoimmune diseases, and ANA prevalence in the US increased between 1988 and 2012. Tobacco smoking decreased during those years while vaping of electronic cigarettes (e-cigarettes) increased after their introduction in 2007. Carbon monoxide (CO) may ameliorate autoimmunity, and e-cigarettes deliver much less CO than regular cigarettes. We explored interdependencies among ANA, smoking, and time. Methods: We analyzed cross-sectional data on ANA and the primary nicotine metabolite, cotinine, in 13,288 participants ≥12 years old from three time periods (1988-1991, 1999-2004, 2011-2012) of the US National Health and Nutrition Examination Survey. Smoking exposure (none, passive, active) was inferred from serum cotinine. We used logistic regression to analyze ANA prevalence, adjusted for sex, age, and race/ethnicity. Results: Over the study periods, ANA prevalence was highest (13.3-19.2%) for nonsmokers but non-trending; lower (11.1-15.5%) for "passive" smokers but steadily increasing; and even lower for active smokers but increasing from 7.4% in 1999-2004 to 13.3% in 2011-2012. The increases in ANA among passive and active smokers were mainly in adolescents (ages 12-19 years). Smokers had reduced odds of ANA in 1999-2004, with an odds ratio (OR) of 0.65 and a 95% confidence interval (CI) of 0.45-0.93, but this association was weaker in 1988-1991 (OR=0.80; 95% CI:0.52-1.22) and 2011-2012 (OR=0.82; 95% CI:0.56-1.21). Discussion: Although smoking causes harmful health effects, ANA data are consistent with it playing a role in decreasing autoimmunity. Recent vaping among adolescents may partially explain their large increase in ANA prevalence. The inverse ANA association with smoking strengthened between 1988-1991 and 1999-2004, but then weakened by 2011-2012. The initial strengthening was potentially because nonsmokers were exposed to progressively less CO (and/or other components of secondhand smoke), due to tightened smoking restrictions, while the potential nicotine-associated protection against ANA may have weakened after e-cigarettes became a source. Smoking should not be recommended given its negative health impacts. However, further studies could elucidate new mechanisms, perhaps involving components of tobacco smoke or vaping, possibly enabling development of novel preventative or treatment measures.