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A4453 - Comparison of Biomarkers of Inflammation and Immune Status in the Nose, Airways, and Serum of E-Cigarette Users and Cigarette Smokers
Author Block: A. Perryman1, J. R. Hoffman2, M. E. Rebuli1, N. E. Alexis3, I. Jaspers3; 1Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, United States, 2Curriculum for the Environment and Ecology, University of North Carolina, Chapel Hill, NC, United States, 3Department of Pediatrics, University of North Carolina, Chapel Hill, NC, United States.
Rationale: E-cigarette use has rapidly increased due to its promotion as a safer alternative to traditional tobacco products and its popularity among never smokers. While cigarette smoke exposure has been demonstrated to have inflammatory and immunosuppressive effects within the airways, the effects of e-cigarette use remain unclear. Our lab has previously shown that e-cigarette use is associated with greater down-regulation of RNA expression for immune-related genes in nasal epithelial cells as compared to cigarette smoking. In addition, e-cigarette use has been shown to be associated with elevated levels of markers of neutrophil activation and mucins in sputum. However, less is known about the effects of e-cigarette use on the comparative levels of inflammatory mediators throughout the respiratory tract and in systemic circulation. Methods: In this study, we generated cytokine profiles for cigarette smokers (n=10), e-cigarette users (n=10), and non-smokers (n=10) using biological specimens collected from the upper and central respiratory tract and systemic circulation. We collected matched samples of epithelial lining fluid (ELF) from the nasal mucosa, nasal lavage fluid (NLF), induced sputum, and serum from healthy volunteers. Smoking category was assessed using self-reported cigarette/e-cigarette use and serum cotinine and urine NNAL levels. Cytokine levels were analyzed by multiplex ELISA. Data were compared across the biological specimens and smoking groups by two-way ANOVA and correlations between specimens determined by linear regression. To adjust for variable dilutions of the biological specimens, the prevalence of cytokines in each biological specimen was ranked. Results: ELF and NLF showed a strong correlation; however, this correlation was driven by the prevalence of different cytokines in each specimen. A comparison of the ranked analytes revealed ELF and sputum clustered together, NLF clustered alone, and serum did not correlate with any of the respiratory specimens. TARC was found to be elevated in the serum of cigarette smokers, but not e-cigarette users. Interferon-inducible chemokines, such as MIG/CXCL9 or I-TAC/CXCL11, were suppressed in e-cigarette users in ELF, NLF, and induced sputum, but only MIG was found to also be suppressed in serum. When stratified by sex, cytokine profiles clustered more closely based on smoking group. Conclusion: Our results suggest that ELF may serve as a better predictor of innate immune status in the lower airways than NLF. Furthermore, decreased expression of immune-orchestrating chemokines such as I-TAC/CXCL11 and MIG/CXCL9, may be indicative of e-cigarette-induced immunosuppressive effects. To better ascertain effects of e-cigarette use, sex differences may need to be considered.