Cytokine signature clusters as a tool to compare changes associated with tobacco product use in upper and lower airway samples

This study compared baseline cytokine signatures in upper and lower airway samples and evaluated how groups of co-expressed cytokines change with tobacco product use. Matched nasal lavage fluid (NLF), nasal epithelial lining fluid (NELF), sputum, and circulating serum samples were collected from 14 non-smokers, 13 cigarette smokers, and 17 e-cigarette users. Samples were analyzed for 22 cytokines, and cytokine signatures were compared across each sample, followed by identification of cytokine clusters with co-modulation patterns within each type of sample, which were subsequently evaluated for potential alterations associated with tobacco product use using eigenvector analyses. Findings included individual cytokine analyses that were carried out using crude, adjusted and stratified models. NELF cytokine clusters and associated tobacco product disruptions were confirmed in an independent validation cohort. Hence, novel systems-level patterns uncovered changes induced by tobacco products, particularly elevations in e-cigarette user nasal eigencytokines and identified that upper airway samples simulate cytokine patterns in lower airways.