PROJECT SUMMARY/ABSTRACT
The proposed K01 application is designed to provide Nancy Jao, Ph.D., with the mentored research and
training necessary to transition into an independent clinical scientist with a tobacco regulatory relevant program
of research. The FDA has long indicated interest in banning menthol as a characterizing flavor in combustible
cigarettes due to its role in facilitating the initiation and use of tobacco products and increasing the number of
smoking-related deaths. Smoking-induced inflammation is a leading pathway by which cigarette smoking
contributes to increased cardiovascular disease (CVD) morbidity and mortality in smokers. Elevations in
biomarkers of inflammation can be detected early, even in asymptomatic individuals, as a subclinical indicator
of CVD risk. Basic science studies have shown that menthol flavoring can cause increases in inflammatory
response and dysfunction beyond the effects of smoking. However, it is unknown whether menthol cigarette
(MC) use may elevate biomarkers of inflammation in smokers and increase CVD risk compared to non-menthol
cigarette (NMC) use. Additionally, while it is expected that a MC ban will improve health outcomes for smokers
who quit or switch to non-combustible products, it is unknown whether there will be reductions in inflammation
for those who switch from MC to NMC smoking. In Study 1, we aim to evaluate differences in biomarkers of
systemic inflammation and CVD risk between MC and NMC smokers in nationally-representative, longitudinal
Population Assessment of Tobacco and Health (PATH) Study. In Study 2, we aim to examine how switching
from MC to NMC smoking may impact biomarkers of systemic inflammation, smoking behavior, and subjective
responses related to smoking. MC smokers (N=68) will be recruited for a five-week study, with one-week of
baseline of MC smoking (Phase 1), followed by four weeks of switching to study-provided, brand-matched
NMCs (Phase 2). Biomarkers of systemic inflammation (e.g., hsCRP, interleukin cytokines) and tobacco
exposure (e.g., cotinine, carbon monoxide) will be analyzed from blood samples before, during, and after
switching. Ecological momentary assessment (EMA) methods will also be gathered to measure patterns of
smoking and smoking-related subjective responses. The proposed research is significant and directly targets
FDA's interest in understanding the impact of flavorings on the health effects of tobacco use. Throughout the
five-year award, Dr. Jao will be mentored by an impressive mentorship team in (1) translational research in
biobehavioral and health effects of tobacco use, particularly relating to biomarkers of inflammation and CVD
risk; (2) longitudinal research methods and advanced statistical analyses, including utilization of the PATH
study dataset and EMA methodology; and (3) design and implementation of human clinical trial studies with
tobacco regulatory implications. Understanding the impact of MC use on these sensitive subclinical biomarkers
prior to CVD diagnosis can help the FDA identify and quantify cardiovascular health hazards of MC use,
particularly for those who may continue to use combustible cigarettes if a MC ban is implemented by the FDA.
