Electronic cigarette uses propylene glycol and glycerol to deliver nicotine and flavors to the lungs. Given the hundreds of different brands, the thousands of flavors available and the variations in nicotine concentrations, it is likely that electronic cigarette settings and e‐liquid composition affect the size distribution of particles emitted and ultimately pulmonary deposition. We used the inExpose e‐cigarette extension to study two separate modes of operation of electronic cigarettes, namely power‐controlled and the temperature‐controlled. We also assessed several e‐liquids based on propylene glycol and glycerol concentrations, nicotine content, and selected monomolecular flavoring agents (menthol, vanillin, and maltol). Particle size distribution was measured using a Condensation Particle Counter and a Scanning Mobility Particle Sizer spectrometer. Lung deposition was predicted using the International Commission on Radiological Protection model. For all resistance coils, increase in power delivery generated larger particles while maintaining a higher coil temperature generated smaller particles. Increase in glycerol concentration led to the generation of larger particles. With regard to flavors, we showed that despite minor effect of menthol and maltol, vanillin dramatically increased particle size. Presence of nicotine also increased particle size. Finally, particles emitted by the electronic cigarette were predicted to mainly deposit in the alveoli and conditions generating larger particle sizes led to a reduction in predicted lung deposition. This study shows that coil temperature, propylene glycol and glycerol concentrations, presence of nicotine, and flavors affect the size of particles emitted by an electronic cigarette, directly affecting predicted lung deposition of these particles.

E‐cigarette use has exploded in the past years, especially among young adults and smokers desiring to quit. While concerns are mostly based on the presence of nicotine and flavors, pulmonary effects of propylene glycol and glycerol inhalation, the main solvents of e‐liquid have not been thoroughly investigated. In this preclinical study, mice were exposed 2 h daily for up to 8 weeks to vapors of propylene glycol and/or glycerol generated by an e‐cigarette. Lung transcriptome analysis revealed it affected the expression level of genes of the circadian molecular clock, despite causing no inflammatory response. Periodical sacrifices showed that the rhythmicity of these regulatory genes was indeed altered in the lungs, but also in the liver, kidney, skeletal muscle, and brain. E‐cigarette exposure also altered the expression of rhythmic genes (i.e., hspa1a and hspa1b), suggesting that alterations to the ‘clock genes’ could translate into systemic biological alterations. This study reveals that the major solvents used in e‐cigarettes propylene glycol and glycerol, not nicotine or flavors, have unsuspected effects on gene expression of the molecular clock that are to be taken seriously, especially considering the fundamental role of the circadian rhythm in health and disease.

Exposure to solar UVB radiation leads to the formation of the highly mutagenic cyclobutane pyrimidine dimers (CPDs), the DNA damage responsible for mutations found in skin cancer. The frequency of CPD formation and the repair rate of those lesions are two important parameters to determine the probability of UVR-induced mutations. Previous work has shown that chronic irradiation with sublethal doses of UVB radiation (chronic low-dose UVB radiation) leads to the accumulation of residual CPD that persists over time. We have thus investigated the persistence, localization, and consequences on genome stability of those chronic low-dose UVB radiation-induced residual CPDs. We show that chronic low-dose UVB radiation-induced residual CPDs persist on DNA and are diluted via semiconservative replication. They are overrepresented in the heterochromatin and at the TT dipyrimidine sites, and they catalyze the incidence of sister chromatin exchange. Our results shed some light on the impact of chronic UVB radiation exposure on DNA, with a focus on residual CPDs, their distribution, and consequences.

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P-positive microvessels. Upon MSS rechallenge, the S1P agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.

Background. Most of electronic cigarette (e-cigarette) users are also smoking tobacco cigarettes. Due to the relative novelty of this habit, very little is known on the impact of vaping on pulmonary health, even less on the potential interactions of dual e-cigarette and tobacco cigarette use. Methods. Therefore, we used well-established mouse models to investigate the impact of dual exposure to e-cigarette vapors and tobacco cigarette smoke on lung homeostasis. Groups of female BALB/c mice were exposed to room air, tobacco smoke only, nicotine-free flavor-free e-cigarette vapors only or both tobacco smoke and e-cigarette vapors. Moreover, since tobacco smoke and electronic cigarette vapors both affect circadian processes in the lungs, groups of mice were euthanized at two different time points during the day. Results. We found that dual-exposed mice had altered lung circadian gene expression compared to mice exposed to tobacco smoke alone. Dual-exposed mice also had different frequencies of dendritic cells, macrophages and neutrophils in the lung tissue compared mice exposed to tobacco smoke alone, an observation also valid for B-lymphocytes and CD4+ and CD8+ T lymphocytes. Exposure to e-cigarette vapors also impacted the levels of immunoglobulins in the bronchoalveolar lavage and serum. Finally, e-cigarette and dual exposures increased airway resistance compared to mice exposed to room air or tobacco smoke alone, respectively. Discussion. Taken together, these data suggest that e-cigarette vapors, even without nicotine or flavors, could affect how the lungs react to tobacco cigarette smoke exposure in dual users, potentially altering the pathological course triggered by smoking.

Cigarette smoke exposure induces inflammation marked by rapid and sustained neutrophil infiltration, IL-1α, release and altered surfactant homeostasis. However, the extent to which neutrophils and IL-1α contribute to the maintenance of pulmonary surfactant homeostasis is not well understood. We sought to investigate whether neutrophils play a role in surfactant clearance as well as the effect of neutrophil depletion and IL-1α blockade on the response to cigarette smoke exposure. In vitro and in vivo administration of fluorescently labeled surfactant phosphatidylcholine was used to assess internalization of surfactant by lung neutrophils and macrophages during or following cigarette smoke exposure in mice. We also depleted neutrophils using anti–Ly-6G or anti–Gr-1 Abs, or we neutralized IL-1α using a blocking Ab to determine their respective roles in regulating surfactant homeostasis during cigarette smoke exposure. We observed that neutrophils actively internalize labeled surfactant both in vitro and in vivo and that IL-1α is required for smoke-induced elevation of surfactant protein (SP)–A and SP-D levels. Neutrophil depletion during cigarette smoke exposure led to a further increase in SP-A levels in the bronchoalveolar lavage and increased IL-1α, CCL2, GM-CSF, and G-CSF release. Finally, macrophage expression of Mmp12, a protease linked to emphysema, was increased in neutrophil-depleted groups and decreased following IL-1α blockade. Taken together, our results indicate that neutrophils and IL-1α signaling are actively involved in surfactant homeostasis and that the absence of neutrophils in the lungs during cigarette smoke exposure leads to an IL-1α–dependent exacerbation of the inflammatory response.

Vaping has become increasingly popular over the past decade. This pragmatic review presents the published biological effects of electronic cigarette vapour inhalation with a focus on the pulmonary effects. Special attention has been devoted to providing the documented effects specific to each major ingredient, namely propylene glycol/glycerol, nicotine and flavouring agents. For each ingredient, findings are divided according to the methodology used, being in vitro studies, animal studies and clinical studies. Finally, we provide thoughts and insights on the current state of understanding of the pulmonary effects of vaping, as well as novel research avenues and methodologies.

Vaping is increasingly popular among the young and adult population. Vaping liquids contained in electronic cigarettes (e‐cigarettes) are mainly composed of propylene glycol and glycerol, to which nicotine and flavors are added. Among several biological processes, glycerol is a metabolic substrate used for lipid synthesis in fed state as well as glucose synthesis in fasting state. We aimed to investigate the effects of glycerol e‐cigarette aerosol exposure on the aspects of glycerol and glucose homeostasis. Adult and young male and female mice were exposed to e‐cigarette aerosols with glycerol as vaping liquid using an established whole‐body exposure system. Mice were exposed acutely (single 2‐h exposure) or chronically (2 h/day, 5 days/week for 9 weeks). Circulating glycerol and glucose levels were assessed and glycerol as well as glucose tolerance tests were performed. The liver was also investigated to assess changes in the histology, lipid content, inflammation, and stress markers. Lung functions were also assessed as well as hepatic mRNA expression of genes controlling the circadian rhythm. Acute exposure to glycerol aerosols generated by an e‐cigarette increased circulating glycerol levels in female mice. Increased hepatic triglyceride and phosphatidylcholine concentrations were observed in female mice with no increase in circulating alanine aminotransferase or evidence of inflammation, fibrosis, or endoplasmic reticulum stress. Chronic exposure to glycerol e‐cigarette aerosols mildly impacted glucose tolerance test in young female and male mice. Fasting glycerol, glucose, and insulin remained unchanged. Increased pulmonary resistance was observed in young male mice. Taken together, this study shows that the glycerol contained in vaping liquids can affect the liver as well as the aspects of glucose and glycerol homeostasis. Additional work is required to translate these observations to humans and determine the biological and potential pathological impacts of these findings.