Acute effects of heated tobacco product (IQOS) aerosol-inhalation on lung tissue damage and inflammatory changes in the lungs.

Introduction Emerging heated tobacco products (HTPs) were designed to reduce exposure to toxicants from combustible cigarettes (CS) by avoiding burning tobacco and instead heating tobacco. We studied the effects of short-term inhalation of aerosols emitted from HTP product called IQOS, on lung damage and immune-cell recruitment to the lungs in mice. Methods Numerous markers of lung damage and inflammation including albumin and lung immune-cell infiltrates, proinflammatory cytokines and chemokines were quantified in lungs and bronchoalveolar (BAL) fluid from IQOS, CS or air-exposed (negative control) mice. Results Importantly, as a surrogate marker of lung epithelial-cell damage, we detected significantly increased levels of albumin in the BAL fluid of both HTP and CS exposed mice compared to negative controls. Additionally, total numbers of leukocytes infiltrating the lungs were equivalent following both IQOS-aerosols and CS inhalation and significantly increased compared to air-exposed controls. We also observed significantly increased numbers of CD4 +IL-17A + T cells, a marker of a T cell immune response, in both groups compared to air controls; however, numbers were the highest following CS exposure. Finally, the numbers of CD4 +RORγt + T cells, an inflammatory T cell subtype expressing the transcription factor that is essential for promoting differentiation into pro-inflammatory Th17 cells, were significantly augmented in both groups compared to air-exposed controls. Levels of several cytokines in BAL were significantly elevated, reflecting a proinflammatory milieu. Conclusions Our study demonstrates that short-term inhalation of aerosols from IQOS generates damage and proinflammatory changes in the lung that are substantially similar to that elicited by CS-exposure. Implications Exposure of mice to heated tobacco product IQOS, one of the candidate modified-risk tobacco products (MRTPs), induces inflammatory immune-cell accumulation in the lungs and augments the levels of proinflammatory cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid. Such an exacerbated pulmonary proinflammatory microenvironment accompanies with lung epithelial-cell damage in IQOS-exposed mice, suggesting a potential association with the impairment of lung function.