Waterpipe Smoking Research Articles

Demographic Factors Affecting Cigarette and Waterpipe Smoking in Hormozgan, Iran

Background: Tobacco consumption is one of the major public health concerns worldwide which can have adverse effects on human health. An awareness of the status of tobacco consumption and identification of its affecting factors constitute the first step in tobacco control programs. The aim of this study was to investigate the prevalence of cigarette and waterpipe consumption among residents in Bandar Abbas in Hormozgan province. Materials and Methods: In general, 853 residents of Bandar Abbas were chosen through the cluster sampling method and by referring to their houses and interviewing them. Data were analyzed by the chi-square test, along with the odds ratio (OR) with a confidence interval (CI) of 95%. Results: The prevalence of cigarette and waterpipe consumption in men and women was 14.8% and 0.9%, as well as 5.6% and 5.4%, respectively. Male gender (OR=18.26; 95% CI: 6.58-50.65), marital status of those married once (OR=2.91; 95% CI: 1.24-6.85), academic education (OR=0.48; 95% CI: 0.25-0.93), father’s diploma and above (OR=0.35; 95% CI: 0.15 – 0.83), mother’s diploma and above (OR=0.36; 95% CI: 0.13-0.99) were associated with cigarette smoking. The other related factors were employee (OR=1.99; 95% CI: 1.20-3.30), self-employed (OR=3.13; 95% CI: 1.87- 5.24), and age (OR=12.57; 95% CI: 2.86-55.24 for age ≥ 50 years). No significant relationship was found between demographic factors and tobacco smoking. Conclusion: Cigarette and waterpipe smoking is a multidimensional health problem and has a close relationship with different demographic and social factors. Planning for enhancing health and mitigating the damages resulting from tobacco consumption is essential for promoting healthcare.

Smoking status and SARS-CoV-2 infection severity among Lebanese adults: a cross-sectional study

BackgroundA paradoxical hypothesis about the effect of smoking on patients infected with severe acute respiratory syndrom 2 (SARS-CoV-2) infection still exists. Furthermore, gender-discrepancy in the impact of smoking on COVID-19 severity was given little attention. Thus, the aims of the present study were to evaluate the prevalence of smoking and the COVID-19 infection severity in a sample of adult patients diagnosed with COVID-19 and to explore the relationship between smoking status and SARS-CoV-2 infection severity in the overall sample and stratified by gender.MethodsA retrospective analytical study was conducted on patients diagnosed with COVID-19 cases between December, 2020 and April, 2021 from three leading laboratories in Lebanon. Sociodemographic characteristics, smoking status and clinical symptoms were collected. Multinomial logistic regression analysis was used to explore the relationship between smoking status and SARS-CoV-2 infection severity.ResultsA total of 901 confirmed COVID-19 cases participated in the study, 50.8% were females. The mean age of patients was 38.4 years (SD = 15.3). Of the total sample, 521(57.8%) were current smokers. Regarding infection severity, 14.8% were asymptomatic, 69.9% had mild symptoms, while 15.3% had severe infection. In the overall sample, smoking status, smoking types and dose–response were not significantly associated with infection severity. Upon stratifying the entire sample by gender, no association was found between all the considered variables with infection severity among females. However, a significant association was found among male with mild infection compared to their asymptomatic counterparts (OR = 1.78 95% CI (1.01–3.13)). Waterpipe smoking was found to be associated with infection severity among male with mild infection (OR 2.64 (95% CI 1.32–5.27)) and severe infection 2.79, 95% CI (1.19–6.53) compared to their asymptomatic counterparts.ConclusionOur fundings highlight sex differences in the association between tobacco smoking and COVID-19 severity. Current tobacco smoking was not associated with SARS-CoV-2 infection severity among female patients, however, tobacco smoking, particularly waterpipe, was found to be associated with infection severity among male. Thus, the battle against smoking should continue by assisting smokers to successfully and permanently quit.

Opium Use and the Risk of Liver Cancer: A Case-Control Study.

The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely.

Discussion of waterpipe tobacco smoking on reddit

ObjectivesThis study aimed to examine public discussions of waterpipe tobacco smoking, as well as the potential associations of different waterpipe flavors with health symptoms, using Reddit data. Study designThis is an observational infodemiology study. MethodsUsing keywords such as “waterpipe”, “hookah”, and “shisha”, Reddit posts were extracted from Reddit Archive (pushshift.io) between February 1, 2016, and December 31, 2020. Temporal analysis was used to understand the longitudinal trend of the discussions about waterpipe tobacco smoking. Topic modeling using the Latent Dirichlet Allocation (LDA) model was performed to examine the topics on waterpipe tobacco. We estimated the conditional probability of having each health problem for each given waterpipe flavor. ResultsThe discussion of waterpipe on Reddit was slowly decreasing from 2016 to 2018 and surged until May 2020. The fruit was the most popular waterpipe flavor and the neurological symptom was the most mentioned health category in waterpipe-related Reddit posts. The most popular topics included “Friends spending time together at night with waterpipe smoking”, “Playing games and smoking waterpipe at a hookah bar”, and “Discussing waterpipe flavors and related products”. Some waterpipe flavors were more associated with certain health problems than others. For example, mint/menthol flavor had a high probability to be associated with symptoms related to throat and mouth. ConclusionThis study provided longitudinal surveillance of waterpipe tobacco smoking discussed on Reddit. We showed the potential relationship between waterpipe flavors and health symptoms, which provides preliminary evidence about the potential health effects of waterpipe tobacco smoking.

Hematological and biochemical changes associated with water-pipe (Shisha)smoking for some volunteers in Missan province

Hematological and biochemical changes associated with water-pipe (Shisha)smoking for some volunteers in Missan province

Prevalence and predictors of waterpipe smoking cessation among young adults in the US: Findings from a population-based study

BackgroundThe prevalence of waterpipe tobacco (WPT) smoking is 9.2 % among young adults aged 18–24 years in the United State (US). Adequate understanding of the factors predicting WPT smoking cessation among the young population is essential to tobacco control efforts. This study assessed the prevalence and predictors of WPT smoking cessation among young adults. MethodsThe population assessment of tobacco and health (PATH) study data (waves 1–5) was used for the study. A total sample of 561 young adults exclusively using WPT (past 30-days) was used for the analysis. The probability of WPT smoking cessation (no use in the past 12 months) was estimated using the Kaplan-Meier survival method, and the predictors were assessed using the Cox proportional hazards regression model. ResultsDuring the five waves, 25.1 % of the young adult WPT smokers quit smoking. Among them, 58.2 % were females and the remaining 41.8 % were males. The Hispanics (40.2 %) had the highest rate of cessation among the ethnic groups. Regret smoking (adjusted hazard ratio (aHR) = 2.33, 95 % confidence interval (CI) = 1.24–4.36), smoking restriction at home (aHR = 2.86, 95 % CI = 1.41–5.88), and living in Midwest geographical region (aHR = 2.11, 95 % CI = 1.16–3.84) increased the likelihood whereas alcohol use (aHR = 0.62, 95 % CI = 0.41–0.93) decreased the likelihood of cessation among the young adult WPT smokers. ConclusionsCommunicating the health and economic consequences associated with WPT smoking (e.g., pictorial health warning labels), involving smoker’s household members in WPT awareness campaigns, and closing regulatory loopholes related to WPT venues will increase the WPT smoking cessation rate among the young population in the US.

National and Regional Fraction of Cancer Incidence and Death Attributable to Current Tobacco and Water-Pipe Smoking in the Eastern Mediterranean Countries in 2020.

We aimed to calculate the Population Attributable Fraction (PAF) of cancers due to tobacco use in the Eastern Mediterranean Region (EMRO), where water-pipe smoking is prevalent but its effect was not considered in previous studies. We applied Levin's formula to estimate PAFs of cancers due to tobacco use (defined as all type tobacco including both cigarette and water-pipe). We also calculated PAF of water-pipe smoking separately. Exposure prevalence data were retrieved from representative national and subnational surveys. Data on cancer incidence and death were also and cancer cases were obtained GLOBOCAN 2020. We also obtained associated relative risks from published meta-analyses. Of the total 715 658 incident adult cancer cases that were reported in 2020 in EMRO, 14.6% (n = 104 800) was attributable to tobacco smoking (26.9% [n = 92 753]) in men versus 3.3% (n = 12 048) in women. Further, 1.0% of incident adult cancers were attributable to current water-pipe use (n = 6825) (1.7% [n = 5568]) in men versus 0.4% (n = 1257 in women). PAFs of cancers due to tobacco smoking in EMRO were higher in our study than previous reports. This could be due to the neglected role of water-pipe in previous studies that is a common tobacco smoking method in EMRO. The proportion of cancers attributable to water-pipe smoking in EMRO might be underestimated due to lack of research on the risk of cancers associated with water-pipe smoking and also less developed cancer registries in EMRO. In this study, we found higher PAFs for cancers due to tobacco smoking in the Eastern Mediterranean (EMR) region than previous reports. This difference could be due to ignoring the role of water-pipe smoking in previous studies. In 2020, 1% of incident cancers and 1.3% of cancer-related deaths in EMRO were attributable to water-pipe smoking. We also found a big difference in PAFs of cancers due to tobacco and water-pipe smoking across EMRO countries, with Tunisia, Lebanon, and Jordan having the highest, and Djibouti, Sudan, and Somalia having the lowest proportions of cancers attributable to tobacco and water-pipe smoking.

A prospective cohort study on the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam

Tobacco consumption, as a worldwide problem, is a risk factor for several types of cancer. In Vietnam, tobacco consumption in the form of waterpipe tobacco smoking is common. This prospective cohort study aimed to study the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam. A total of 25,619 eligible participants were followed up between 2008 and 2019. Waterpipe tobacco and cigarette smoking data were collected; semi-quantitative food frequency and lifestyle questionnaires were also utilized. Gastric cancer mortality was determined via medical records available at the state health facilities. A Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). During 314,992.8 person-years of follow-up, 55 men and 25 women deaths due to gastric cancer were identified. With never-smokers as the reference, the risk of gastric cancer mortality was significantly increased in participants who were ever-smoking (HR = 2.43, 95% CI = 1.35–4.36). The positive risk was also observed in men but was not significantly increased in women. By types of tobacco use, exclusive waterpipe smokers showed a significantly increased risk of gastric cancer mortality (HR = 3.22, 95% CI = 1.67–6.21) but that was not significantly increased in exclusive cigarette smokers (HR = 1.90, 95% CI = 0.88–4.07). There was a significant positive association between tobacco smoking and gastric cancer death for indicators of longer smoking duration, higher frequency per day, and cumulative frequency of both waterpipe and cigarette smoking. Waterpipe tobacco smoking would significantly increase the risk of gastric cancer mortality in the Vietnamese population. Further studies are required to understand the waterpipe tobacco smoking-driven gastric cancer burden and promote necessary interventions.

Magnitude of the smoking problem, knowledge, attitude and practice, among family members of primary school students


 Background: smoking is a very important public health problem, urgently requiring immediate and effective measures due to its harmful effect on health. The purpose of this study was to collect baseline information about the magnitude of smoking problem, knowledge, attitude, and practice among family members of primary school students in the northwest region of Iran.
 Methods: of 55 680 primary school students (the 3th, 4th and 5th grades), 7.1% (n=3 954) were selected using randomized multi-stage cluster sampling. Data collection was conducted in April, May, and June 2011, by means of a self-administered two-page questionnaire.
 Results: a total of 3 954 students (57.6% boys and 42.3% girls) with the mean age of 10.46±1.09 years were evaluated. According to our data, the prevalence of cigarette smoking among fathers was more than other family members (27.1% versus 17.8%) whereas the prevalence of water pipe smoking among fathers and other family members was almost similar (9.2% and 9.7% respectively). None of the smoking type was prevalent among mothers (cigarette: 1% and water pipe: 1.1%). Considerable numbers of all students under study had been exposed to secondhand smoke at home (cigarette: 19.8% and water pipe: 7.7%).
 Conclusions: considering our findings, two procedures recommended to prevail the problem are to provide greater education about hazards of tobacco consumption among students and their family; and to legislate new laws by officials to ban tobacco use at home.

Vitamins B9 and B12 in adolescents smoking cigarettes and waterpipe combined

Vitamins B9 and B12 in adolescents smoking cigarettes and waterpipe combined

Influence of the COVID-19 pandemic on causes for the development of carbon monoxide intoxications

Introduction: Several causes can lead to carbon monoxide (CO) intoxication. A first-line treatment option for such intoxications is hyperbaric oxygenation (HBO2) therapy. The COVID-19 pandemic has been changing everyday life in Germany since March 2020, mainly caused by statutory provisions. Our aim was to review whether these changes have an influence on the causes and frequency for the development of CO intoxication. Methods: We retrospectively analyzed the data of patients who were treated for CO intoxication in our institution between April 2019 and March 2021. Besides demographic data, we compared the overall number and documented causes for each CO intoxication in the period of April 2020 to March 2021 with the period between April 2019 and March 2020. Results: After applying inclusion and exclusion criteria, 139 patients were included. We found a significant decrease in the overall number of patients who needed treatment since the beginning of the COVID-19 pandemic. However, the share of CO intoxication caused by the indoor use of coal stoves, coal barbecue, or suicide attempts increased. In contrast, the share of cases caused by apartment or house fire, smoking waterpipe, or gas stoves decreased. Conclusion: The COVID-19 pandemic and the associated restrictions lead to a significant reduction in the number of patients in need for HBO2 therapy due to CO-Intoxication. The causes leading to CO intoxication also changed since the beginning of the COVID-19 pandemic. We observed a shift toward causes related to the indoor use of coal-fired stoves and barbecues as well as suicide attempts.

Gender differences in the price elasticity of demand for waterpipe and cigarette smoking in Lebanon, Jordan and Palestine: a volumetric choice experiment

ObjectivesThis study assessed the extent to which the elasticity of cigarette and waterpipe tobacco products differs between men and women. We also explored the levels of substitution and complementarity in...

Effect of Shisha (Water-Pipe) Smoking on Serum Lipid Profile and Antioxidant Vitamins among Smokers in Kano Metropolis

Shisha Smoking is a risk factor for coronary heart diseases. The smoke contains large amount of chemicals which are capable of generating reactive oxygen species which play an important role in oxidative stress which in turn leads to the development and progression of many disorders such as hypertension, cancer, diabetes mellitus and cardiovascular diseases. Monitoring lipid profile (HDL-cholesterol, LDL-cholesterol and triacylgycerides) and antioxidant vitamins (A, C and E) levels is very important to give an insight on the effect of shisha smoking on lipid profile and antioxidant vitamins. This study aimed to determine the effect of shisha smoking on serum lipid profile, and antioxidant vitamins in fifty (50) apparently healthy shisha smokers (exposed group) in Kano metropolis. A corresponding fifty (50) apparently healthy non-smokers were used as controls (non exposed group). The Shisha smoking was significantly associated with increased levels of total cholesterol (TC), triglyceride, LDL-cholesterol (p˂0.05) in smokers compared to control group. However, there was a significant (p>0.05) decrease in HDL-cholesterol and serum antioxidant vitamins (A, C and E) in exposed group compared to non-exposed group. The results of this study also indicate that exposure of human being to shisha smoke over a period of time causes slight increase in lipid profile and antioxidant vitamins but the relation was statistically not significant (p>0.05). The findings suggest that shisha smoking causes dyslipidaemia and oxidative stress.

The Combined Outcomes of the COVID-19 Pandemic and a Collapsing Economy on Mental Well-Being: A Cross-Sectional Study.

Objective: This study aimed to examine the outcomes of COVID-19 and a collapsing economy on the mental well-being (MWB) of the general Lebanese population. Methods: A cross-sectional study was conducted online in May 2020 and enrolled 502 adults. Results: Mental well-being had a mean of 14.80 (14.37; 15.24). A lower MWB was associated with female gender (beta=−1.533 [−2.324; −0.743]), university education (beta=−2.119 [-3.353;-0.885]), fear of COVID-19 (beta=−0.131 [−0.199; −0.063]), fear of poverty (beta=−0.232 [−0.402;−0.063]), verbal violence at home (beta=−3.464 [−5.137; −1.790]), and chronic disease (beta=−1.307 [−2.283; −0.330]). Better family satisfaction (beta=0.380 [0.235; 0.525]) and better financial situation (beta=0.029 [0.003; 0.055]) were significantly correlated with better MWB. In the subsample of workers/looking for a job, additional factors affected MWB: physical exercise (beta =1.318 [0.370; 2.265]) was associated with better QOL, while being a previous waterpipe smoker, being self-employed before the crisis (beta=−1.22 [−2.208;−0.231]), working from home since the economic crisis (−1.853 [−3.692; −0.013]), and worrying about the long-term effects of the crisis on one’s employment status (beta=−0.433 [−0.650; −0.216]) were associated lower MWB. It is noteworthy that closure of the institution yielded a borderline result (B = −1.2; p = .094), while the fear of COVID-19 was not significantly associated with MWB (B = −0.054; p =0.192). Conclusion: This study showed that, during the pandemic, economic and other factors, directly or indirectly related to COVID-19, significantly affected quality of life. The fear of COVID-19 and fear of poverty mainly impacted the MWB of the general population. However, the fear of COVID-19 lost its significance among workers, who reported that factors negatively affecting their MWB are directly related to their employment and the already collapsing economy in Lebanon.

Knowledge and Use of Electronic Cigarettes in Young Adults in the United Arab Emirates, Particularly during the COVID-19 Pandemic.

(1) Background: The popularity of electronic cigarettes (e-cigarettes) has recently increased. Although they are less harmful than regular cigarettes, they still cause health consequences and their use for smoking cessation is inconclusive. The objective of this study was to evaluate patterns of use, knowledge about, and attitude towards e-cigarettes among youth in the United Arab Emirates (UAE) while also researching the impact of the COVID-19 pandemic on smoking behavior. (2) Methods: An online cross-sectional survey was distributed across three major universities in the UAE (n = 240) between March and November 2021. Descriptive analysis, comparison across gender and nationality groups, and correlates between 30-day e-cigarette use and self-reported increases in nicotine consumption during the pandemic were studied. (3) Results: About 37% of students had used an e-cigarette in their lifetime, and 23% had smoked e-cigarettes in the past month. During the pandemic, 52% of university students self-reported no change in nicotine consumption, while only 17.5% had reported an increase. The current smoking of regular cigarettes, waterpipe, and medwakh increased the odds of having an increase in smoking during the pandemic by 5.3 times. (4) Conclusions: The findings inform about youth behavior and knowledge about vaping in the UAE and could also support the development of awareness interventions.

Water pipe smoking among public versus private university students in Ankara, Turkey: an online survey

BackgroundWater pipe smoking has become a global public health problem as its popularity increased over time, especially among youth. The objective of our study was to estimate water pipe tobacco smoking prevalence and to assess socioeconomic factors associated with ever water pipe smoking by public and private university students in Ankara, Turkey.MethodsThis descriptive study was based on a survey conducted among public (n=2685) and private (n=2485) university students via an online questionnaire on demographics and water pipe consumption patterns. For every student in the sample, a socioeconomic status index was calculated using principal component analysis. Binary logistic regressions for the outcome variable of ever-using water pipe yielded estimates of adjusted odds ratios (aORs) for the associated factors such as the respondent’s age, gender, university type, and socioeconomic status.ResultsThe prevalence of ever use of water pipe was 69.1% (95% CI: 67.2-70.9%) among private and 59.1% (95% CI: 57.2-60.9%) among public university students. A substantial share of ever users were current users (25.5% in private versus 21.6% in public, p=0.008). On average, private university students had higher socioeconomic status than public university students (for example, access to a car (51.7% versus 35.8%, p=0.008), financial support from family (71.5% versus 65.1%, p<0.001)), also demonstrated by a higher socioeconomic status index. Being a private university student (aOR 1.57, 95% CI: 1.38-1.79), older (aORs 1.50 to 2.39, p<0.001), male (aOR 2.36, 95% CI:2.06-2.70), as well as having greater financial resources, such as having access to a car (aOR 1.24, 95% CI:1.07-1.42), or having income support from family (aOR 1.32, 95% CI:1.13-1.54), were associated with ever-using water pipe. A higher SES index was significantly associated with higher odds of ever using water pipe among both private (aOR 1.13, 95% CI:1.06,1.20) and public university (aOR 1.12, 95% CI:1.06,1.19) students.ConclusionsWater pipe smoking was common in both public and private universities; however, private university students had higher odds of ever using water pipe. There is an urgent need to implement evidence-based interventions, taking into account the socioeconomic status of young adults, to prevent them from water pipe smoking.

Waterpipe smoking: Results from a population-based study in Qatar.

INTRODUCTIONWaterpipe smoking is common in the Eastern Mediterranean Region and is becoming more prevalent in Qatar. To better plan waterpipe smoking control strategies we aimed to: 1) determine the prevalence of waterpipe smoking and explore its patterns in Qatar; 2) describe the knowledge, attitudes, and practices related to smoking behaviors; 3) recognize locations of waterpipe smoking and symptoms experienced during waterpipe sessions; and 4) evaluate the frequency of waterpipe smoking and the initiation age.METHODSWe analyzed the data of a 7921 population-based survey of adults aged ≥18 years (nationals and expatriates), conducted in Qatar between March and December 2019. Out of 7105 surveys collected, 6904 were complete and included in the analysis.RESULTSOf the 6904, 570 (8.3%; 95% CI: 7.7–9.0) were waterpipe tobacco smokers, 425 (10.6%) males and 145 (5.1%) females. The highest prevalence of waterpipe smoking was reported among people aged 18–24 years (10.6%). Of the 575 waterpipe smokers, 56.3% (n=324) were exclusive waterpipe smokers. Use of other tobacco products among waterpipe smokers was higher among Qataris (52.3%) than expatriates (37.7%). Waterpipe cafés were the most common location for waterpipe smoking, however, females preferred restaurants; 83.3% reported that waterpipe smoking is harmful, while 39.3% considered that it is less harmful than cigarette smoking.CONCLUSIONSWaterpipe smoking prevalence is considerably high in Qatar, the second form of tobacco used. The formulation of new policies and enforcement of regulatory restrictions on waterpipe smoking are essential to reduce its uptake. Expansion in tobacco cessation services for women and poly-tobacco users is needed.

Genomic Analysis of Waterpipe Smoke-Induced Lung Tumor Autophagy and Plasticity.

The role of autophagy in lung cancer cells exposed to waterpipe smoke (WPS) is not known. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed that WPS activated autophagy, as reflected by LC3 processing, in lung cancer cell lines. The autophagy response in smokers with lung adenocarcinoma, as compared to non-smokers with lung adenocarcinoma, was investigated further using the TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. The results, based on a machine learning classification model using Random Forest, indicate that smokers have an increase in autophagy-activating genes. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to non-smoker patients indicates a higher tumor mutational burden, a higher CD8+ T-cell level and a lower dysfunction level in smokers. While the expression of the checkpoint genes tested—PD-1, PD-L1, PD-L2 and CTLA-4—remains unchanged between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 were found to be higher in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two groups. Therefore, targeting autophagy in lung adenocarcinoma patients, in combination with checkpoint inhibitor-targeted therapies or chemotherapy, should be considered in smoker patients with lung adenocarcinoma.

Abstract 223: Chronic exposure to waterpipe smoke elicits immunomodulatory and carcinogenic effects in the lung

Abstract 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 WPS-exposed 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. Citation Format: Zahraa Rahal, Maya Hassane, Nareg Karaoghlanian, Jiexin Zhang, Ansam Sinjab, J. Jack Lee, Maria Gabriela Raso, Junya Fujimoto, Hassan Chami, Alan Shihadeh, Humam Kadara. Chronic exposure to waterpipe smoke elicits immunomodulatory and carcinogenic effects in the lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 223.

Abstract 2995: Autophagy as a key driver of waterpipe smoke-induced lung cancer cell plasticity and resistance

Abstract Smoking is the number one risk factor for lung cancer and tobacco smokers are at 20 to 40 times higher risk of developing lung cancer in comparison to non-smokers. We have previously shown that exposing lung cancer cell lines to tobacco smoke condensate generated from waterpipe (WP) interferes with cell proliferation, cell plasticity, DNA damage and tumor cell recognition and killing by natural killer (NK) cells. Global transcriptomic analysis identified an expression profile of genes that best distinguished treated and non-treated cells involving several pathways including those involved in epithelial to mesenchymal transition (EMT) and stemness. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed an activation of autophagy as reflected by LC3 and P62 in lung cancer cell lines in response to WPS. Interestingly, our data revealed that WPS-induced EMT and cancer stemness involved autophagy induction. The autophagy response in smokers with lung adenocarcinoma as compared to non-smokers with lung adenocarcinoma was investigated using TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. Preliminary results based on a machine learning classification model using Random Forest indicate that smokers have an increase in autophagy activating genes as compared to non-smokers. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to patients who have not had any active exposure to smoke indicate a higher tumor mutational burden, CD8+ T-cell level and lower dysfunction level in smokers. Multivariate regression analyses confirm these results even after controlling for confounding factors like age, gender, and tumor stage. While the checkpoint genes tested PD1, PDL1, PDL2 and CTLA-4, had no difference between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 had higher expression in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two cohorts. Therefore, targeting autophagy in lung adenocarcinoma patients in combination with checkpoint inhibitors, targeted therapies or chemotherapy should be considered in smoker patients with lung adenocarcinoma. Citation Format: Rania F. Zaarour, Mohak Sharda, Bilal Azakir, Goutham Hassan Venkatesh, Raefa Abou Khouzam, Ayesha Rifath, Zohra Nizami, Fatima Abdullah, Fatin Mohammad, Husam Nawafleh, Yehia ElSayed, Salem Chouaib. Autophagy as a key driver of waterpipe smoke-induced lung cancer cell plasticity and resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2995.