Background: Alcohol, marijuana and tobacco are the most common recreationally used substances in United States (US). However, unlike alcohol and tobacco, marijuana is an illicit substance. The increasing support for reclassification of marijuana as legal substance necessitates investigating its effect on health. These studies seek to examine the relationship of marijuana and tobacco with metabolic syndrome (a precursor of cardiovascular diseases - the primary cause of morbidities and mortalities). Method: Data from 2011 public-use linked mortality file of the National Center for Health Statistics, Centers for Disease Control and Prevention, and 2005-2006 & 2011-2012 US National Health and Nutrition Examination Survey was used to estimate the effect of marijuana and tobacco on metabolic syndrome. Odds ratios from logistic regression analyses were determined using four main diagnostic criteria for metabolic syndrome. Odds ratios were compared using: National Cholesterol Education Program Adult Treatment Panel III, World Health Organization, European Group for the study of Insulin Resistance and International Diabetes Federation definitions of metabolic syndrome. Hazard ratios (HRs) for cardiovascular mortality were estimated using cox proportional hazard regression. Results: Each year of marijuana use was associated with increased odds of metabolic syndrome [OR=1.05 (95% CI: 1.01, 1.09)] and hypertension [OR=1.04 (95% CI: 1.01, 1.07)]. Each additional year of cigarette smoking was associated with increased odds of hypertension [OR=1.03 (95% CI: 1.00, 1.06)] and hyperglycemia [OR=1.03 (95% CI: 1.01, 1.05)]. Adjusted HR for hypertension mortality for marijuana users compared to non-marijuana users was 3.42 (95% CI: 1.20, 9.79) and 1.04 (95% CI: 1.00, 1.07) for each year of marijuana use. Conclusion: Prolonged years of marijuana use was associated with increased odds of metabolic syndrome and hypertension irrespective of the criteria used to define metabolic syndrome. Our results also indicate that marijuana use is associated with increased risk for hypertension mortality. The association between prolonged use of marijuana and risk of cardiovascular morbidities and mortalities requires further investigation whilst developing global public health policies regarding legalization of marijuana use.

The prevalence of waterpipe smoking exceeds that of cigarettes among adolescents in the Middle East where waterpipe is believed as less harmful, less addictive and can be a safer alternative to cigarettes. This dissertation tested the gateway hypothesis that waterpipe can provide a bridge to initiate cigarette smoking, identified the predictors of cigarette smoking progression, and identified predictors of waterpipe smoking progression among a school-based sample of Jordanian adolescents (mean age ± SD) (12.7 ±0.61) years at baseline. Data for this research have been drawn from Irbid Longitudinal Study of smoking behavior, Jordan (2008-2011). The grouped-time survival analysis showed that waterpipe smoking was associated with a higher risk of cigarette smoking initiation compared to never smokers (P < 0.001) and this association was dose dependent (P < 0.001). Predictors of cigarette smoking progression were peer smoking and attending public schools for boys, siblings’ smoking for girls, and the urge to smoke for both genders. Predictors of waterpipe smoking progression were enrollment in public schools, frequent physical activity, and low refusal self-efficacy for boys, ever smoking cigarettes, friends’ and siblings’ waterpipe smoking for girls. Awareness of harms of waterpipe among boys and seeing warning labels on the tobacco packs by girls were protective against waterpipe smoking progression. In Conclusion, waterpipe can serve as a gateway to cigarette smoking initiation among adolescents. Waterpipe and cigarette smoking progressions among initiators were solely family-related among girls, and mainly peer-related among boys. The unique gender differences for both cigarette and waterpipe smoking among Jordanian adolescents in Irbid call for cultural and gender-specific smoking prevention interventions to prevent the progression of smoking among initiators.

MPH / Department of Public Health / Background: Globally, cigarette smoking is causing preventable deaths in developing countries affecting especially the youth. Historically, cigarette smoking is known to be more common among adults but is also becoming common among students. Purpose: The study aimed to investigate factors contributing to cigarette smoking and its health consequences amongst students of the University of Venda in South Africa. Methodology: A quantitative approach using a descriptive cross- sectional design was adopted. Convenience sampling was used to randomly select 428 respondents. A self-reporting questionnaire with closed ended questions was administered to respondents between the ages of 17-40 years who suited the inclusion criteria. Permission to conduct the research was obtained from the Ethics Committee of the University of Venda. Data were analysed using SPSS version 23 and presented in the form of tables and charts. Pearson’s chi squares were used to test significant relationships between variables and smoking status. Results: A total of 407 students participated in the study. Of the 407, 208 (51%) of respondents were female students. The mean age of the study population was 24 years. Of these 407, 175(43%) reported being smokers 232 (57%) were nonsmokers. More smokers were observed among the male respondents and registered for first and second years. There was a significant relationship between age, gender, religion, school of affiliation, amount of pocket money and smoking status (P-value=0.05).The results showed that the majority of the respondents285 (70%) agreed to the belief that students smoked cigarettes due to availability of cigarettes at every corner of the campus, 281 (79%) peer influenced by friends 289 (71%) family members who smoke, and 313 (76.8%)increase social interaction. The majority of the students were knowledgeable about health consequences caused by smoking. Nonsmoking students were more knowledgeable about harmful effects of smoking as compared to smokers (P=0.00. Conclusion: The study concludes that students smokes cigarettes due to being a friend with someone who smokes, being in new a environment, stress, depression, observation of other students smoking, no signage prohibiting smoking and lack of knowledge regarding health / NRF

The purpose of this study was to determine how to best motivate smokers with schizophrenia or schizoaffective disorder to seek treatment for tobacco dependence. Smokers with schizophrenia or schizoaffective disorder (N=78) were randomly assigned to receive a Motivational Interviewing, Psychoeducational, or Minimal Control intervention. A greater proportion of participants receiving the Motivational Interviewing intervention followed through on a referral for tobacco dependence treatment within one-week and one-month post-intervention. Mixed model Analyses of Variance found no differences between groups at one-week or at one-month with respect to tobacco use or motivation to quit. Within group analyses indicated that participants in the Motivational Interviewing and Psychoeducational groups reported significant decreases in cigarettes smoked per day. Only participants in the Motivational Interviewing group showed significant increases in confidence in their ability to quit smoking.

Indiana University-Purdue University Indianapolis (IUPUI) / Cigarette smoking (CS) continues to be a significant modifiable factor contributing to a variety of diseases including cardiovascular, pulmonary and renal pathologies. It was suggested that smoking have detrimental effect of the body’s progenitor cells of bone marrow and peripheral organs. Since the concept of cell therapy that utilizes adipose stem/stromal cells (ASC) is gaining momentum it becomes critical to assess the therapeutic activities of the progenitors isolated from smokers. This study has revealed that CS negatively impacts the vasculogenic potential of ASC, in vitro, as well as weakening their therapeutic activity in vivo when tested in mouse model of hindlimb ischemia. We hypothesized that the decrease in vasculogenic activity of ASC is attributed to a higher level of expression of an angiostatic factor Activin A by ASC from CS donors. These findings clearly suggest that smokers should be evaluated for potential exclusion from early clinical trials of autologous cell therapies, or assessed as a separate cohort. The donor’s health status should be considered when choosing between autologous vs allogeneic cell therapies. We then examined the effect of CS on development of kidney pathology in mice. CS exposure led to decrease in kidney weights, capillary rarefaction, and cortical blood perfusion, and in parallel led to increase in kidney fibrosis and iron deposition. Interestingly, infusion of healthy ASC to the mice following CSexposure reversed CS-induced damages. This strongly support the notion that ASC-based therapy may provide rejuvenation effect. In the other subset of studies, we hypothesized that CS-induced lung emphysematous changes are preceded by suppression of bone marrow (BM) hematopoietic progenitor cells (HPC). We have revealed that intermittent BM mobilization with AMD3100 may mitigate the CS-induced myelo-suppression and deterioration of lung function and morphology. We observed that treatment of mice with AMD3100, while exposed to CS, preserves HPC at the levels of healthy control mice. Furthermore, AMD3100 treatment preserved lung parenchyma from pathological changes. These data suggest that while CS has a myelo-suppressive effect, administration of AMD3100 preserved BM-HPC and ameliorated lung damage.

Indiana University-Purdue University Indianapolis (IUPUI) / The smoking rate of low-income pregnant women is almost 4 times the rate for higher-income women. A better understanding of smoking within the low-income population is needed. The purpose of this dissertation was to study smoking and related factors for pregnant and postpartum women living in poverty. The first component used Rodger’s evolutionary concept analysis method and uncovered three attributes, four antecedents, and three consequences for smoking cessation. The second (N = 1,554) and third (N = 71,944) components were a secondary data analysis of first-pregnancy Medicaid-eligible women enrolled in the Nurse-Family Partnership program from 2011-2016. The second component explored patterns of smoking and depression and their associations. Eight distinct patterns of smoking and depression were found. Smokers were more likely than nonsmokers to have depressive symptoms at the end of pregnancy (OR = 1.37 [1.04, 1.81] and 12 months post-delivery (OR = 1.93 [1.47, 2.51]. The third component investigated covariates present during early pregnancy and their relationships with smoking status and sought to find best fitting predictive models. Multivariable logistic regression showed cigarette use in the 3 months prior to pregnancy and at program intake were significant predictors for smoking status at the end of pregnancy and 12 months post-delivery. Interactive Matrix Language, Structured Query Language, and iterations of logistic regression identified 5 covariates (high school education, cigarette use prior to pregnancy, smoking status at pregnancy baseline, depression, and self-mastery) for the best fitting model at the end of pregnancy and three additional covariates (post-secondary education, marital status, and race) for the 12 months post-delivery model. The area under the receiver operator characteristic curve was 0.9681 for the end of pregnancy model and 0.9269 for 12 months post-delivery model, indicating excellent prediction ability of the models. Results can be integrated in smoking prevention education, screening, and cessation intervention programs.

No description available.

Pulmonary tuberculosis (TB) remains one of the most infectious causes of death worldwide. Mycobacterium tuberculosis (M.tb), the causative agent of TB is transmitted via infectious aerosols, and in the majority of cases the bacteria is effectively controlled, by the host, resulting in a chronic latent infection. Currently, the only available vaccine is the Bacillus Calmette-Guérin (BCG), which despite being successful in preventing childhood disseminated forms of TB, has failed to control the adult pulmonary TB epidemic. One of the major contributing factors in the failure of the BCG is that although antigen-specific T cells are present at the time of M.tb infection, the recruitment of such T cells into the site of infection is significantly delayed. This delay, while reduced compared to non-vaccinated hosts, allows the bacteria to replicate unchecked within the lung and establish a “foothold” prior to the arrival of protective T cells and subsequent immune control. Thus, novel initiatives seek to close this “immunological gap” through increasing the level of protective T cell responses within the airway mucosa immediately following M.tb infection. We therefore investigated the impact of deliberate modulation of T cell geography following BCG vaccination on the outcome of pulmonary M.tb infection. In addition, a number of environmental factors are also thought to affect the site of M.tb infection: the respiratory mucosa. However, little is currently known about the effects of environmental exposure to allergens and other substances such as cigarette smoke on the outcome of pulmonary TB. Throughout this thesis we have investigated the mechanisms of immune protection and failure of protection against pulmonary M.tb infection within the respiratory mucosa. / Thesis / Doctor of Philosophy (Medical Science)

S100 calcium-binding protein A9 (S100A9) is elevated in plasma and bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9- mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9 were higher in older mice compared with in young animals and coincided with pulmonary function changes. Both acute and chronic exposure to cigarette smoke enhanced S100A9 levels in age-matched mice. To examine the direct role of S100A9 on the development of COPD, S100a9 -/- mice or mice administered paquinimod were exposed to chronic cigarette smoke. S100A9 depletion and inhibition attenuated the loss of lung function, pressure-volume loops, airway inflammation, lung compliance, and forced expiratory volume in 0.05 s/forced vital capacity, compared with age-matched wild-type or vehicleadministered animals. Loss of S100a9 signaling reduced cigarette smoke-induced airspace enlargement, alveolar remodeling, lung destruction, ERK and c-RAF phosphorylation, matrix metalloproteinase- 3 (MMP-3), matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and keratinocyte- derived chemokine (KC) release into the airways. Paquinimod administered to nonsmoked, aged animals reduced age-associated loss of lung function. Since fibroblasts play a major role in the production and maintenance of extracellular matrix in emphysema, primary lung fibroblasts were treated with the ERK inhibitor LY3214996 or the c-RAF inhibitor GW5074, resulting in less S100A9-induced MMP-3, MMP-9, MCP-1, IL-6, and IL-8. Silencing Toll-like receptor 4 (TLR4), receptor for advanced glycation endproducts (RAGE), or extracellular matrix metalloproteinase inducer (EMMPRIN) prevented S100A9-induced phosphorylation of ERK and c-RAF. Our data suggest that S100A9 signaling contributes to the progression of smoke-induced and age-related COPD.

Indiana University-Purdue University Indianapolis (IUPUI) / The complex pathogenesis of emphysema involves disappearance of alveolar structures, in part attributed to alveolar cell apoptosis. The mechanism by which cigarette smoke (CS) induces alveolar cell apoptosis is not known. We hypothesized that ceramides are induced by CS via specific enzymatic pathways that can be manipulated to reduce lung cell apoptosis. CS increased ceramides in the whole lung and in cultured primary structural lung cells. Exposure to CS activated within minutes the acid sphingomyelinase, and within weeks the de novo- ceramide synthesis pathways. Pharmacological inhibition of acid sphingomyelinase significantly attenuated CS-induced apoptosis. To understand the mechanisms by which ceramides induce apoptosis, we investigated the cell types affected and the involvement of RTP801, a CS-induced pro-apoptotic and pro-inflammatory protein. Direct lung augmentation of ceramide caused apoptosis of both endothelial and epithelial type II cells. Ceramide upregulated RTP801 and the transgenic loss of RTP801 inhibited only epithelial, but not endothelial cell apoptosis induced by ceramide. In conclusion, CS induces acid sphingomyelinase-mediated ceramide upregulation and apoptosis in a cell-specific manner, which in epithelial cells involves induction of stress response proteins that may further amplify lung injury. Molecular targeting of amplification pathways may provide therapeutic opportunities to halt emphysema progression.