Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease in the elderly. It is currently the fourth leading cause of death and will become the third by 2030. Cigarette smoke is the major cause of COPD pathogenesis, resulting from the burden of oxidants, which stimulates the production of inflammatory chemokines, leading to the influx of inflammatory cells into the airways and causing chronic inflammation. Due to lung infection by bacteria, such as Pseudomonas Aeruginosa during acute exacerbation in COPD, cigarette smoking might induce an immunosuppressive effect, which leads to bacteria colonization in the airways and further contributes to the chronic inflammation in the airway of COPD. Furthermore, cigarette smoke-induced production of reactive oxygen species (ROS) also plays an important role in the pathogenesis of COPD, however, N-acetyl-L-cysteine (NAC), which has been administered for the treatment of COPD as a mucolytic agent, also showed antioxidant and anti-inflammatory effect. The exact mechanism or cellular pathway through which cigarette smoke suppresses bacteria-induced inflammatory response and how NAC acts as an anti-inflammatory agent still remains uncertain. This study aims to investigate the effect of cigarette smoke and lipopolysaccharide (LPS) alone or in combination on the release of pro-inflammatory chemokines and to elucidate cigarette smoke-induced chemokines release in the presence and absence of NAC. Both cigarette smoke and LPS alone induced the release of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1).Cigarette smoke suppressed the LPS-induced IL-8 and MCP-1release. NAC reduced both basal and cigarette smoke-induced secretion of these inflammatory chemokines. Moreover, Western blot demonstrated that cigarette smoke activated AMPKα phosphorylation, which was suppressed with NAC pretreatment, suggesting that NAC might have inhibitory effect on the release of chemokine release via the AMPK pathway. Our current data suggests that there may be a link between ROS generation to AMPK activation and chemokine release in BEAS-2B cells. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

An approach to smoking through an analysis of its representations, grounded in the medicalization literature, highlights the inadequacies of a narrow medical perspective and some of its negative implications. This does not require that we abandon the medical discourse, but stresses the importance of setting it in a wider representational context. Drawing on the work of Saussure, Barthes, Eco and Foucault, the author constructs a theory of interaction amongst representations suited to both discourse and images. To investigate the medicalization of smoking, four empirical studies are reported which include quantitative and qualitative approaches to press reporting at both macro-and micro-levels, cigarette advertising and packaging. There have been medical representations of smoking since the introduction of tobacco into Britain. However, a thematic analysis of tobacco-related reporting in the Times newspaper (1946-1995) found that these representations have expanded and diversified, becoming increasingly linked to other representations (e.g. financial) and generating new themes (e.g. discrimination, litigation). Medical representations, however, are contested and subject to subversion by alternative representations, including libertarian and alternative medical constructions of smoking. These processes are investigated in a detailed structural and rhetorical analysis of a contemporary newspaper article, together with related correspondence and cartoons. Quantitative and qualitative analyses of 754 UK cigarette advertisements from four national newspapers (1946-1995) identified an increase in medical and packaging-related representations of smoking and a decrease in financial representations, representations of the act of smoking and of cigarettes as social currency. The final, questionnaire, study (with 60 participants) found, among other things, a clear and consensually-held system of health-related signification in contemporary UK cigarette packaging in ratings of packets. The thesis concludes with a discussion of the implications of medicalization for smoking-related policy and for the smoker, and of smoking for the medicalization literature.

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Thesis (M. Soc. Sc.)--University of Hong Kong, 1994. / Includes bibliographical references (leaves 87-89).

Thesis (M.Soc.Sc.)--University of Hong Kong, 1994. / Includes bibliographical references (leaves 87-89) Also available in print.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2010. / Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (leaves 69-80).

Magister Scientiae Dentium - MSc(Dent) / Introduction: Saliva is a significant biological fluid involved in the maintenance of good oral health. Cigarette smoking exerts detrimental effects on oral health and has been shown to affect saliva, but with no consensus regarding its effect on the quantity (flow rate) and quality (pH) of the saliva. Aim: To assess the effect of cigarette smoking on the flow rate and pH of whole stimulated saliva. Method: A case control study was conducted using patients who presented at the UWC Oral Health Centre patient sifting/waiting area. The patients who agreed to participate were assessed for inclusion into the study until the sample size was (n=60), stratified by smoking (n=30) and non-smoking (n=30). Stimulated saliva samples were collected in specimen jars by asking patients to chew a sterilized rubber band for 5 minutes and spit the contents into the specimen jar provided at 1 minute intervals. The specimens were transported to the laboratory within 30 minutes to measure the salivary quantity and pH. Results: No statistically significant difference in the salivary flow rates was found between smokers and non smokers (p=0.5273). Smokers showed a statistically significant decrease in their pH compared to non smokers (p=0.028). Conclusion: Cigarette smoking reduces the salivary pH, thereby producing an acidic environment.

Cigarette smoke is the leading cause of preventable mortality worldwide. This excess death is attributable to an increased risk of acquiring a variety of conditions, including chronic respiratory/cardiovascular diseases and various types of cancer. Smokers are additionally predisposed to develop infectious diseases, notably including pneumonia caused by the influenza virus, one of the most prevalent and burdensome pathogens in existence today. Although cigarette smoke is well known to modulate many aspects of the immune system, the specific mechanisms by which this predisposition is mediated are incompletely understood. Also unclear is the effect of cigarette smoke on responses to intranasal immunization strategies aimed at eliciting immunity against pathogens such as influenza in the upper airways, where protection may substantially contribute to sterilizing immunity. This PhD thesis focused primarily on addressing these knowledge gaps. In the first study, we assessed the effect of cigarette smoke on antibody induction following intranasal immunization in the upper airways of mice, finding that smoke exposure attenuated antigen-specific IgA induction in the upper respiratory tract, reproductive tract, and systemic circulation. In addition, we found that these nasal IgA demonstrated a reduced antigen-binding avidity in the acute post-immunization period. Mechanistically, deficits in nasal IgA were associated with a reduced accumulation of antigen-specific IgA antibody-secreting cells (ASCs) in the nasal mucosa, induction of these cells in nasal-draining lymphoid tissues, and upregulation of molecules critical to ASC homing (vascular cell adhesion molecule-1; VCAM-1) and IgA transepithelial transport (polymeric immunoglobulin receptor; pIgR) in the nasal mucosa. Ultimately, in tandem with recent clinical work published by others, our study strongly suggests that cigarette smoke can attenuate IgA induction in the upper airways, which may have implications for aspects of intranasal vaccine efficacy. Thus, smoking status should be more consistently considered in the design of clinical trials for IgA-oriented intranasal vaccines. The second study did not assess smoking and host defense directly, but rather served to optimize protocols for assessing immunoglobulins in human mucoid respiratory samples as a precursor to future studies in smoking-related disease. In this regard we found that, relative to phosphate-buffered saline (PBS), dithiothreitol (DTT)-based processing of human sputum samples increased total IgA yields, decreased IgE yield, and improved the detection of a specific IgG autoantibody. These findings suggest that processing choices for human mucoid respiratory samples should be made with specific goals in mind as they pertain to antibody isotype(s) of interest. Finally, in the third study we investigated potential mechanisms by which cigarette smoke exposure promotes influenza, given that smokers are at increased risk of acquiring the pathogen, progressing to severe disease, and being admitted to hospital/ICU following infection. In doing so, we found that concurrent smoke exposure increased morbidity, hypoxemia, pulmonary edema, neutrophilia, and ultimately mortality in a mouse model of H1N1 infection. These changes were associated with an increased accumulation of viral (v)RNA in cells independent of any change in the shedding of replication-competent viral particles. Using a novel dysregulation score approach, we found that interleukin (IL)-6 and colony-stimulating factor (CSF)3 expression was highly exacerbated in the lungs and circulation of smoke-exposed, infected mice relative to controls. Supplementation of recombinant (r)CSF3 increased morbidity, hypothermia and edema, while blockade of the cognate receptor (CSF3R) improved alveolar-capillary barrier function. On the cellular level, single cell RNA-sequencing revealed a shift in the distribution of Csf3+ cells towards neutrophils. Finally, deep transcriptional analysis of neutrophils revealed a gene signature that was largely indicative of an exacerbated form of typical disease with select unique regulatory elements. Ultimately, this work identifies potential therapeutic targets (CSF3R signaling, excess vRNA accumulation) for the treatment of cigarette smoke-augmented influenza, and warns against clinical rCSF3 therapy to treat neutropenia during viral infectious disease. In conclusion, the work presented in this PhD dissertation expands our understanding of the relationship between cigarette smoke and antimicrobial host defense as it pertains to both IgA immunity in the upper airways, and the pathogenesis of cigarette smoke-augmented influenza. / Thesis / Doctor of Philosophy (PhD) / Cigarette smoke exposure is well known to have many harmful effects on human health, including through its ability to promote various infectious diseases such as influenza. However, the mechanisms by which it promotes infection are not fully known. This is an important knowledge gap given that over 1.1 billion individuals continue to smoke worldwide, and a large number of people are exposed to the harmful effects of second-hand smoke, both with fatal consequence. The central goal of this thesis was to gain a better understanding of this relationship between cigarette smoke and infectious disease, specifically by assessing how smoke exposure impacts immune responses in the upper and lower airways. In the first study, we found that smoke exposure interferes with the ability to activate immunoglobulin (Ig)A antibody responses in the nasal passages of mice, which may have important implications for human nasal vaccination strategies. The second study investigated different methods with which to best measure antibodies in human respiratory samples. Finally, in the third study we defined a role for a specific molecule, CSF3, in worsening health in a mouse model of concurrent cigarette smoke and influenza infection. Overall, this work provides new insights into the ways in which smoking can increase the risk of respiratory infection, thereby informing the future design and testing of vaccines and treatments for use in our highly smoke-exposed global population.

published_or_final_version / Management Studies / Master / Master of Business Administration