Résumé
Effects of waterpipe smoking on lung pathobiology and carcinogenesis remain sparse despite the worldwide emergence of this tobacco vector as a socially acceptable form of smoking, particularly among the youth. To address this gap, we investigated the effects of chronic waterpipe smoke (WPS) exposure on lung pathobiology, host immunity, and tumorigenesis using both an experimental animal model and an exploratory observational analysis of human waterpipe smokers and non-smokers. Mice exposed to increasing doses of WPS (once or five times per week for 20 weeks), through an exclusively devised exposure system for this study, were more prone to develop lung tumors compared to control-air exposed littermates. This effect was accompanied by various pro-tumor immune phenotypes, including increased IL-17A+ levels in T/B cells as well as elevated expression of the immune checkpoint PD-L1 and the pro-inflammatory cytokine IL-1β in myeloid cells. While flow cytometry analysis revealed increased CD4 and CD8 T cell infiltration in WPSexposed mice, gene signatures of cytotoxic and expanded immune response were, conversely, decreased in animals exposed to heavy WPS relative to control air. Interestingly, mice heavily exposed to WPS exhibited increased expression of Tmprss4, Cd55, and Ace2, cell receptors and mediators of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and, thus, COVID-19 pathogenesis. We also perform RNA-sequencing analysis of bronchial airway epithelial brushings of cancer-free waterpipe smokers and non-smokers undergoing diagnostic bronchoscopy. Transcriptomes of normal airway cells in waterpipe smokers, relative to waterpipe non-smokers, harbored gene programs that were associated with poor clinical outcomes in lung adenocarcinoma (LUAD) patients, alluding to a WPS-associated molecular injury, like that established in response to cigarette smoking. Overall, our analyses demonstrate immunomodulatory and carcinogenic effects of WPS on the murine and human lung. Our study also shows that WPS exposure leads to a field of injury that may be associated with increased risk for lung cancer. This study is unique for interrogating carcinogenic effects of chronic exposure to WPS with the longest, to our knowledge, follow-up time in vivo. Our findings accentuate the need for additional studies that can guide evidence-based policies to counteract shortfalls in public health control of waterpipe smoking.
Résumé
This research compared university student-athletes and other university students to analyze differences in attitudes towards COVID-19. The objective was to examine the impact of student-athletes' attitudes on their future athletic activities and perform verification that will contribute to the deliberation and creation of university support measures for student-athletes. Google Forms were used to administer an online questionnaire to university students nationwide. The responses to questions on the questionnaire were recorded on either 5 or 8 point scales, as well as open-ended questions without word limitations at the end of the questionnaire. The results were analyzed by separating results into two cohorts;student-athletes and other university students, and then categorizing responses to each question as positive or negative. Cross-tabulation was used and then Fischer's exact test was performed. To analyze the open-ended questions, KH-Coder3 software, which excels at Japanese analysis and is used in a great deal of research, was used. The analysis found a significant difference for some questions. In particular, a greater percentage of student-athletes than other university students felt unease regarding infection at university facilities, the impact of infection on university life, and the impact on activities from April 2020 onwards. Some of the reasons for the higher percentage of responses indicating unease were the lack of transparency in student life, with universities not defining clear approaches.