Rationale. Cigarette smoking is a well-known risk factor for cardiovascular disease, including arterial diseases such as atherosclerosis and abdominal aortic aneurysm. However, our understanding of how exposure to cigarette smoke impacts arterial disease pathogenesis is not well known. Consequently, this doctoral thesis focuses on understanding the development of atherosclerosis and aortic aneurysm in the context of exposure to cigarette smoke. In particular, since monocytes and macrophage are key immune cells implicated in arterial pathology, this work concentrates on understanding the impact of cigarette smoke exposure on the function and kinetics of monocytes and arterial macrophages. Main Findings. Using a mouse model that combines two clinically relevant risk factors, hyperlipidemia and cigarette smoke, we showed that smoke exposure increases atherosclerosis and induces the spontaneous formation, progression, and rupture of abdominal aneurysms. We also provide experimental evidence that atherosclerosis strongly associates with regions of elastin damage and arterial dilation, suggesting atherogenesis may directly contribute to abdominal aneurysm formation. Given the importance of macrophages in arterial disease, we investigated arterial macrophage heterogeneity and function following exposure to cigarette smoke. We report that cigarette smoke exposure increased the abundance of arterial monocytes and macrophages, whereas heterogeneity was primarily driven by hypercholesterolemia in aneurysmal tissue. Specifically, hypercholesterolemia is associated with an increase in macrophage populations with putative functions in inflammation and tissue remodelling including Trem2 foamy macrophages, inflammatory macrophages, and interferon-inducible macrophages. Moreover, we demonstrated that arterial macrophages play a critical role in elastin fragmentation within the arterial wall of smoke exposed mice. Finally, we investigated the impact of cigarette smoke on kinetic factors that can contribute to arterial macrophage accumulation. We found that, despite increased development of arterial disease, exposure to cigarette smoke is associated with an overall suppression of circulating monocytes and pro-inflammatory cytokines. Using a parabiosis model, we show monocyte recruitment is significantly increased and is likely a key factor contributing to accumulation of arterial macrophages following exposure to cigarette smoke. We also present evidence suggesting that endothelial dysfunction, related to a loss of endothelial nitric oxide synthase, contributes to increased arterial monocyte recruitment following exposure to cigarette smoke. Conclusions and Significance. Overall, we provide evidence that atherosclerosis likely contributes to abdominal aneurysm pathology in a model of cigarette smoke-induced aneurysm formation. We further provide insight into how tobacco smoke promotes arterial disease development through increased local accumulation of arterial macrophages despite suppressed monopoiesis and systemic inflammation. We identify monocyte recruitment and endothelial dysfunction as key factors contributing to the increased accumulation of arterial macrophages, with no overall differences in macrophage heterogeneity, following smoke exposure. In addition to providing insight into the increased risk of arterial disease following exposure to cigarette smoke, this study also provides experimental evidence that atherogenesis can contribute to abdominal aneurysm pathology. Overall, this thesis furthers our understanding of arterial disease pathogenesis and can provide a foundation for further mechanistic or therapeutic focused research aimed at reducing the burden of cardiovascular disease. / Thesis / Doctor of Philosophy (PhD) / Diseases that affect the heart and major blood vessels are one of the leading causes of illness and death worldwide. Atherosclerosis is one such disease caused by the buildup of fatty deposits in the walls of major blood vessels called arteries. This buildup can eventually block the artery and lead to a heart attack or stroke. Abdominal aortic aneurysms are another type of disease that affects arteries. In this case, the walls of the artery grow weak and begin to balloon out until the artery eventually breaks causing severe internal bleeding and death. One of the most important cells involved in the development of atherosclerosis and aneurysms is the macrophage, a type of white blood cell that is an important part of the immune system and found in diseased arteries. Although we know that cigarette smoking is one of the most significant risk factors for developing atherosclerosis and abdominal aneurysms, we do not fully understand why. Therefore, the goal of this thesis project was to investigate how cigarette smoke affects the development of arterial disease with a focus on understanding how it impacts the movement and function of macrophages. Using a mouse model, we found that the development of atherosclerosis and aneurysm are likely related, and also identified ways that exposure to cigarette smoke increases the numbers of macrophages in arteries. This work advances our understanding of how arterial diseases may be related and provides insight into how smoking can increase the risk of developing arterial disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality, with the potential to afflict as many as half of the 1.1 billion smokers in the world. The inflammatory response to cigarette smoke is believed to mediate the progressive and irreversible loss of lung function that characterizes COPD. The greatest burden of the disease arises from episodes of worsened symptoms and inflammation, usually triggered by microbial infection. Currently, the mechanisms that drive cigarette smoke-induced inflammation are being elucidated but ambiguity remains about this response and the inflammatory response engaged in a smoke-exposed lung experiencing a microbial infection. This thesis sought to investigate inflammatory mediators induced by cigarette smoke and those induced by bacteria, the most common cause of infectious exacerbations of COPD, in the context of smoke exposure. In chapter two we investigated the role of Breast Regression Protein-39 (BRP-39), a gene commonly observed to be increased under inflammatory conditions, in the inflammatory response to cigarette smoke. In order to determine the mechanisms of BRP-39 induction, its expression and inflammation was assessed in IL-13, IL-18, and IL-1R1 deficient mice. BRP-39 was found to be redundant in cigarette smoke-induced inflammation, but these data confirmed that IL-1R1 was a crucial mediator of this response. After examining the inflammatory response elicited by smoke alone, we investigated the importance of IL-1 signaling in a model of bacterial exacerbation of cigarette smoke-induced inflammation. We found that the exacerbated neutrophilia that typifies the response of a smoke-exposed lung to bacteria was dependent on IL-1α-mediated production of the CXCR2 ligand CXCL5. This study identified the unique phenomenon that cigarette smoke primes alveolar macrophages to produce excessive amounts of IL-1α in response to bacterial stimuli. The purpose of the final study of the thesis was to more comprehensively characterize the extent to which cigarette smoke changes the phenotype of macrophages. Examining total gene expression by microarray found that smoke-exposed alveolar macrophages were in a proliferative state expressing a unique profile of inflammatory mediators. Further analysis revealed that this was likely the result of a pulmonary environment rich in growth factors. Taken together, these data provide detail to the understanding of the biological process of inflammation that drives the pathogenesis of COPD. These studies identify a phenomenon that predisposes smokers to experience more severe responses to bacteria and reinforces the targeting of IL-1 signaling in the treatment of COPD. / Thesis / Doctor of Philosophy (Medical Science)

The Memphis, Tennessee National Weather Service (NWS) currently has issues with their atmospheric dispersion index (LVORI), and is looking for a new index that better represents smoke dispersion in their County Warning Area (CWA). Forecast soundings at hour 00 and hour 48 from the North American Mesoscale (NAM) model were collected at various locations in the southeastern United States. Using the data collected, a new index equation was developed. A bootstrapping analysis was performed to determine if the mean index number corresponding to low visibility was statistically significantly different and greater than the mean index number corresponding to high visibility for forecast hour 00 and hour 48. Based on the results of this study, the mean index number was greater for low visibility, but was not statistically significantly different for forecast hour 00. For forecast hour 48, the mean index number was greater and statistically significantly different for low visibility.

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No description available.

The purpose of this study was to investigate the prevalence of smoke-free environment polices throughout the Commonwealth of Virginia at worksites employing fifty or more workers. Specifically, this study assessed policy prevalence, development, implementation, and enforcement. In addition, this study assessed smoke-free environment policy effectiveness. The population for this investigation consisted of telephone surveys of 374 worksites located throughout the Commonwealth of Virginia. Of these worksites, 340 (91%) completed the telephone survey. The population (n = 340) was spread throughout five health regions, Northern, Northwest, Central, Southwest, and East. Descriptive analysis and One-way Analysis of Variance (ANOVA) were applied to investigate differences between these five health regions. An alpha of .05 was selected for this study. Based on the findings, the following conclusions were drawn: (1) Fifty-percent of the worksites located throughout the Commonwealth of Virginia have some form of smoke-free environment policies; (2) The smoke-free environment policy constructs used in the telephone survey guide were statistically significant in identifying differences between the five health regions; (3) Smoke-free environment policies at the worksite are dependent upon health region; (4) Implementation of smoke-free environment policies is dependent upon health region; (5) Enforcement of smoke-free environment policies is dependent upon health region, and (6) Effectiveness of smoke-free environment policies is dependent upon health region. The following recommendations were suggested: (1) Further studies assessing smoke-free environment policy enforcement should be conducted annually; (2) Studies incorporating a qualitative research methodology regarding smoke-free environment policy prevalence should be conducted; (3) Studies involving common smoke-free environment policies at different states should be investigated, and (4) Additional in-depth surveys should be conducted to evaluate health outcomes associated with the implementation of smoke-free environment policies. / Ph. D.

Prescribed burning (Rx) has become increasingly subjected to various regulations. Among these regulations are ordinances that restrict downwind impacts of smoke from prescribed fires. Regulations can severely limit burn managers and private landowners from using Rx as a forest management tool. This research can help us move away from these simplistic regulations, and help promote a regulatory environment in which scientific tools and knowledge are used to prohibit only activities for which the evidence suggests there will be adverse consequences. This research was divided into three parts that consisted of: (1) a pilot validation of the smoke emission model VSMOKE-GIS; (2) review of southeastern states' smoke management guidelines (SMG); and (3) a geographic analysis of Virginian's current SMG. VSMOKE-GIS showed good accuracy in predicting the PM2.5 concentration and location of the smoke plume downwind. Criteria were identified when managing Rx smoke and the strengths, weaknesses, and implications were discussed of the Rx programs. The geographic analysis demonstrated quantitatively how much area may be impacted with minimal apparent benefit. This research should provide a clearer spatial picture of the smoke management barriers associated with Rx on private woodlands in Virginia. These results should be a useful tool in developing a regulatory environment that encourages Rx when the conditions are optimal. We conclude with future recommendations for Virginia. / Master of Science

Environmental tobacco smoke (ETS) has been well established as a danger to children. Exposure to secondhand smoke can cause coughing and wheezing, bronchitis, pneumonia, ear infections, asthma, and sudden infant death syndrome (SIDS). Childhood exposure to ETS may also increase the risk of developing leukemia and lymphoma in childhood (Mitchell, 1997) as well as developing lung cancer as an adult (Glantz, 1992). Despite the great strides recently made in the implementation of regulatory measures to safeguard children from ETS in public places like schools, there remains significant concern regarding children's exposure at home and in their out-of-home care facilities (Ashley and Ferrence, 1998, Jarvis, 2000). In 1996, the Centers for Disease Control and Prevention estimated that there were 336,749 Virginia youth exposed to ETS in the home (State Tobacco Control Highlights, 1999). The purpose of this study was to ascertain the number of family day home providers who allow smoking in their home and/or those that have some type of smoking policy. The sample consisted of 746 licensed, registered or locally approved family day home providers through the Department of Social Services. Of these childcare providers, 81.5% (n=608) completed a questionnaire about their tobacco use policy and its effects. An overwhelming majority (94.7%) of providers reported having a tobacco use policy in their family day home. Most of the providers, 67.6% indicated that smoking was allowed outdoors only while 26.3% noted that smoking was not allowed anywhere at any time, indoor or outdoor. Other policy specifics and background information are discussed in the study. The implications of these findings and recommendations for future training and educational programs for family day home providers are also reviewed. / Master of Science

BACKGROUND: Results of the Global Adult Tobacco Survey in Kerala, India found that 42 % of adults were exposed to second hand smoke (SHS) inside the home. Formative research carried out in rural Kerala suggests that exposure may be much higher. Numerous studies have called for research and intervention on SHS exposure among women and children as an important component of maternal and child health activities. METHODS: Community-based participatory research was carried out in Kerala. First, a survey was conducted to assess prevalence of SHS exposure in households. Next, a proof of concept study was conducted to develop and test the feasibility of a community-wide smoke free homes initiative. Educational materials were developed and pretested in focus groups. After feasibility was established, pilot studies were implemented in two other communities. Post intervention, surveys were conducted as a means of assessing changes in community support. RESULTS: At baseline, between 70 and 80 % of male smokers regularly smoked inside the home. Over 80 % of women had asked their husband not to do so. Most women felt powerless to change their husband's behavior. When women were asked about supporting a smoke free homes intervention, 88 % expressed support for the idea, but many expressed doubt that their husbands would comply. Educational meetings were held to discuss the harms of second hand smoke. Community leaders signed a declaration that their community was part of the smoke free homes initiative. Six months post intervention a survey was conducted in these communities; between 34 and 59 % of men who smoked no longer smoked in their home. CONCLUSIONS: The smoke free homes initiative is based on the principle of collective efficacy. Recognizing the difficulty for individual women to effect change in their household, the movement establishes a smoke free community mandate. Based on evaluation data from two pilot studies, we can project that between a 30 and 60 % reduction of smoking in the home may be achieved, the effect size determined by how well the smoke free home steps are implemented, the characteristics of the community, and the motivation of community level facilitators.

Background: Tobacco smoke exposure (TSE) is unequivocally harmful to children's health, yet up to 48% of children who visit the pediatric emergency department (PED) and urgent care setting are exposed to tobacco smoke. The incorporation of clinical decision support systems (CDSS) into the electronic health records (EHR) of PED patients may improve the rates of screening and brief TSE intervention of caregivers and result in decreased TSE in children. Objective: We propose a study that will be the first to develop and evaluate the integration of a CDSS for Registered Nurses (RNs) into the EHR of pediatric patients to facilitate the identification of caregivers who smoke and the delivery of TSE interventions to caregivers in the urgent care setting. Methods: We will conduct a two-phase project to develop, refine, and integrate an evidence-based CDSS into the pediatric urgent care setting. RNs will provide input on program content, function, and design. In Phase I, we will develop a CDSS with prompts to: (1) ASK about child TSE and caregiver smoking, (2) use a software program, Research Electronic Data Capture (REDCap), to ADVISE caregivers to reduce their child's TSE via total smoking home and car bans and quitting smoking, and (3) ASSESS their interest in quitting and ASSIST caregivers to quit by directly connecting them to their choice of free cessation resources (eg, Quitline, SmokefreeTXT, or SmokefreeGOV) during the urgent care visit. We will create reports to provide feedback to RNs on their TSE counseling behaviors. In Phase II, we will conduct a 3-month feasibility trial to test the results of implementing our CDSS on changes in RNs' TSE-related behaviors, and child and caregiver outcomes. Results: This trial is currently underway with funding support from the National Institutes of Health/National Cancer Institute. We have completed Phase I. The CDSS has been developed with input from our advisory panel and RNs, and pilot tested. We are nearing completion of Phase II, in which we are conducting the feasibility trial, analyzing data, and disseminating results. Conclusions: This project will develop, iteratively refine, integrate, and pilot test the use of an innovative CDSS to prompt RNs to provide TSE reduction and smoking cessation counseling to caregivers who smoke. If successful, this approach will create a sustainable and disseminable model for prompting pediatric practitioners to apply tobacco-related guideline recommendations. This systems-based approach has the potential to reach at least 12 million smokers a year and significantly reduce TSE-related pediatric illnesses and related costs.