Do alternative tobacco products induce less adverse respiratory risk than cigarettes?

RATIONALE: Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke. OBJECTIVES: To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC. METHODS: Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed. MAIN RESULTS: EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A+ T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance. CONCLUSIONS: HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination.

Not all vaping is the same: differential pulmonary effects of vaping cannabidiol versus nicotine.

RATIONALE: Vaping has become a popular method of inhaling various psychoactive substances. While evaluating respiratory effects of vaping have primarily focused on nicotine-containing products, cannabidiol (CBD)-vaping is increasingly becoming popular. It currently remains unknown whether the health effects of vaping nicotine and cannabinoids are similar. OBJECTIVES: This study compares side by side the pulmonary effects of acute inhalation of vaporised CBD versus nicotine. METHODS: In vivo inhalation study in mice and in vitro cytotoxicity experiments with human cells were performed to assess the pulmonary damage-inducing effects of CBD or nicotine aerosols emitted from vaping devices. MEASUREMENTS AND MAIN RESULTS: Pulmonary inflammation in mice was scored by histology, flow cytometry, and quantifying levels of proinflammatory cytokines and chemokines. Lung damage was assessed by histology, measurement of myeloperoxidase activity and neutrophil elastase levels in the bronchoalveolar lavage fluid and lung tissue. Lung epithelial/endothelial integrity was assessed by quantifying BAL protein levels, albumin leak and pulmonary FITC-dextran leak. Oxidative stress was determined by measuring the antioxidant potential in the BAL and lungs. The cytotoxic effects of CBD and nicotine aerosols on human neutrophils and human small airway epithelial cells were evaluated using in vitro air-liquid interface system. Inhalation of CBD aerosol resulted in greater inflammatory changes, more severe lung damage and higher oxidative stress compared with nicotine. CBD aerosol also showed higher toxicity to human cells compared with nicotine. CONCLUSIONS: Vaping of CBD induces a potent inflammatory response and leads to more pathological changes associated with lung injury than vaping of nicotine.

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 cigarette smoke (CS) by avoiding burning tobacco and instead heating tobacco. We studied the effects of short-term inhalation of aerosols emitted from HTP 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 with negative controls. Total numbers of leukocytes infiltrating the lungs were equivalent following both IQOS aerosols and CS inhalation and significantly increased compared with 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 with 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 proinflammatory Th17 cells, were significantly augmented in both groups compared with 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 IQOS, one of the candidate modified-risk tobacco products, induces inflammatory immune-cell accumulation in the lungs and augments the levels of proinflammatory cytokines and chemokines in the BAL fluid. Such an exacerbated pulmonary proinflammatory microenvironment is associated with lung epithelial-cell damage in IQOS-exposed mice, suggesting a potential association with the impairment of lung function.