Background and Objectives: Little is known about the impact of nicotine replacement therapy (NRT) use duration on smoking cessation in the general population. This study determines whether duration of NRT use is associated with smoking cessation. Methods: Data were from the Ontario Tobacco Survey longitudinal study of a population-based cohort of baseline smokers who made serious quit attempts during 18 months of follow-up. The association between NRT (any NRT, patches, or gum) use duration and smoking cessation outcomes (short-term abstinence ≥1 month and long-term abstinence ≥12 months) was estimated by Poisson regression, adjusting for all confounding variables. Results: Among the 1,590 eligible smokers, 933 (59%) did not use any NRT, 535 (34%) used NRT <8 weeks, and 112 (8%) used NRT ≥8 weeks at follow-up. The median duration of NRT use was 14 days. A consistent “J” shape of associations between quit aid use duration and smoking cessation outcomes (quit rates) was found. Using any NRT, patches, or gum <8 weeks was generally associated with a lower likelihood of quitting, but using them ≥8 weeks was generally associated with a higher likelihood of quitting, compared to not using them. Only using patches for the recommended duration (≥8 weeks) was associated with a higher likelihood of short-term (relative risk, RR 1.74, 95% confidence interval, CI 1.21-2.50) and long-term (RR 2.62, 95% CI 1.25-5.50) abstinence at the end of 18 months of follow-up, compared to not using patches. Using gum ≥8 weeks was not associated with short- or long-term abstinence at the end of 18 months of follow-up. Conclusions: Using nicotine patches for the recommended duration is associated with successful short- and long-term abstinence in the general population. More efforts are needed to encourage smokers to use nicotine patches for eight or more weeks when attempting to quit.

Background and Objectives: Little is known about the impact of nicotine replacement therapy (NRT) use duration on smoking cessation in the general population. This study determines whether duration of NRT use is associated with smoking cessation. Methods: Data were from the Ontario Tobacco Survey longitudinal study of a population-based cohort of baseline smokers who made serious quit attempts during 18 months of follow-up. The association between NRT (any NRT, patches, or gum) use duration and smoking cessation outcomes (short-term abstinence ≥1 month and long-term abstinence ≥12 months) was estimated by Poisson regression, adjusting for all confounding variables. Results: Among the 1,590 eligible smokers, 933 (59%) did not use any NRT, 535 (34%) used NRT <8 weeks, and 112 (8%) used NRT ≥8 weeks at follow-up. The median duration of NRT use was 14 days. A consistent “J” shape of associations between quit aid use duration and smoking cessation outcomes (quit rates) was found. Using any NRT, patches, or gum <8 weeks was generally associated with a lower likelihood of quitting, but using them ≥8 weeks was generally associated with a higher likelihood of quitting, compared to not using them. Only using patches for the recommended duration (≥8 weeks) was associated with a higher likelihood of short-term (relative risk, RR 1.74, 95% confidence interval, CI 1.21-2.50) and long-term (RR 2.62, 95% CI 1.25-5.50) abstinence at the end of 18 months of follow-up, compared to not using patches. Using gum ≥8 weeks was not associated with short- or long-term abstinence at the end of 18 months of follow-up. Conclusions: Using nicotine patches for the recommended duration is associated with successful short- and long-term abstinence in the general population. More efforts are needed to encourage smokers to use nicotine patches for eight or more weeks when attempting to quit.

This dissertation is a historically comparative study of adult mortality between Taiwan and the United States throughout the 20th century. The 20th century was characterized by the largest rise in life expectancy at birth and the most rapid decrease in mortality in recorded human history. This dissertation aims not only to examine and compare the trends and levels of life expectancy in Taiwan and the United States over an extended period of time, but also to evaluate the extent to which smoking behavior and obesity play an important role in the recent levels of adult mortality in the United States. I used logistic models of mortality to examine and compare the trends and levels of life expectancy in Taiwan from 1906 to 2008 and in the United States from 1933 to 2007. Second, I re-estimated life expectancy by introducing smoking-attributable mortality to further compare the levels of life expectancy between the two countries. Third, I estimated event history models to investigate whether and how smoking behavior and obesity are related to mortality in the United States in the 1990 to 2006 and the 2000 to 2006 periods. At the end of the 20th century, the level of life expectancy at birth for females in the U.S. was higher than in Taiwan, but they were close. In this century, however, the level of life expectancy at birth in Taiwan has increased to a higher level than in the U.S. The levels of male life expectancy at birth for the two countries are similar in this century, but there were significant differences in the 20th century. The great improvements in juvenile, background and senescent mortality rates in Taiwan may be used to explain this correspondence of life expectancy between the two countries today. Besides, higher smoking-attributed mortality can also serve as another possible reason for the stagnant levels of life expectancy in the U.S. Finally, smoking-related and obesity-related mortality have become progressively more important as predictors of adult mortality in the U.S. in past decades.

Background and Rationale: There is a well-documented practice gap in the rates at which evidence-based smoking cessation treatments are delivered to patients in primary care settings. Multi-component intervention that combine practice, provider, and patient-level supports have been shown to increase the rates at which primary care providers deliver smoking cessation treatments to patients and increase rates of smoking abstinence amongst patients. The incremental value of adjunct telephone-based smoking cessation counselling when delivered as part of a multi-component intervention has not been examined. Aim: The primary objective of this study was to determine whether adjunct telephone-based smoking cessation follow-up counselling (FC), when delivered as part of a multi-component intervention program within primary care clinics is associated with increases in (a) the delivery of evidence-based smoking cessation treatments, (b) patient quit attempts, and (c) patient smoking abstinence when compared to the provision of practice and provider supports (PS) alone. The secondary objective of this study was to determine whether the introduction of a multi-component smoking cessation program is associated with increased delivery of evidence-based smoking cessation treatments by primary care providers and patient smoking outcomes, compared to pre-intervention rates. The study also sought to examine the association between patient, provider, clinic and implementation factors, and study outcomes. Methods: A two-group, pre-post cluster randomized controlled trial was conducted. Eligible clinics were randomly assigned to the PS group or FC group. Both groups were supported with implementing a multi-component intervention program that involved outreach facilitation visits, provider training, real time provider prompts and patient tools, and performance feedback. Clinics assigned to the FC group were also able to refer patients who smoke to a telephone-based follow-up support program for supplemental counselling support. An exit survey was completed with a cross-sectional sample of patients who smoked daily at each study clinic before and after the introduction of the intervention program, and all patients were contacted 4 months later to complete a brief telephone-based interview. Outcome measures included the rate at which evidence-based smoking cessation treatments (5As: ask, advise, assess, assist, arrange) were delivered to patients, the number of patients who made a quit attempt, and patient smoking abstinence at the 4-month follow-up. All data was analyzed using multi-level hierarchical modelling. Results: Seven family medicine clinics and 115 providers were enrolled in the study. A total of 12,585 patients were screened, and 835 eligible patients (mean age 45.8 SD± 14.6, 41% male) who smoke participated in the study. Contrary to the study hypothesis, a higher and statistically significant 7-day point prevalence abstinence (OR 6.8, 95% CI 2.1-21.7; p=<0.01) and continuous abstinence (OR 13.7, 95% CI 2.1-128.3; p=<0.05) rate was observed in the PS group compared to the FC group at the post-assessment after controlling for differences in smoking cessation rates between intervention groups during the baseline period. The introduction of the multi-component intervention program was associated with higher rates of provider 5As delivery and patient quit attempts compared to baseline, with no differences between groups documented. The odds ratios (OR) and 95% confidence intervals (CI) for 5As delivery between the pre- and post-intervention assessments for both intervention groups combined were: “ask” (OR 1.5; 95% CI 1.1, 2.0); “advise” (OR 2.0; 95% CI 1.5, 2.7); “assess” (OR 2.1; 95% CI 1.6, 2.9); “assist” with cessation (OR 2.30; 95% CI 1.70, 3.12); “arrange” (OR 1.9; 95% CI 1.2, 3.0); and “patient quit attempts” (OR 1.4; 95% CI 1.04, 1.94). Differences in 7-day point prevalence abstinence were not statistically significant between the pre- and post-intervention assessments (OR 1.5; 95% CI 0.94, 2.5). The study documented intra-provider variability in the rates at which evidence-based smoking cessation treatments are delivered to patients. Patient characteristics (readiness to quit, time to first cigarette, previous quit attempt in the last year), and the purpose of the clinic visit being for an annual health exam were associated with higher rates of 5As delivery. Conclusion: This is the first study to evaluate a multi-component smoking cessation intervention within the primary health care setting in Canada. The study findings demonstrate that the introduction of a multi-component intervention program in primary care settings was associated with significant improvements in the rates at which providers deliver evidence-based smoking cessation treatments, and increase patient quit attempts. The added value of adjunct telephone counselling was not evident at the 4-month follow-up. The conclusions that can be drawn from the present study are limited by the study design and sample size. A larger trial is required to conclusively determine the impact of the program on long-term smoking abstinence and examine the importance of clinic-level variables in explaining observed differences between study clinics.

My essay explores the public view on smoking in Sweden over the last few decades. I've studied how changes in social structures through media, laws, studies and education has brought about a change in the opinions about smoking. I found that even though there have always been different opinions on smoking it seems to have become less accepted in the Swedish society, particularly in the past twenty years. I discuss the different reason as to why (and how) the view on smoking might have changed the last decades amongst the Swedish people. To be able to do this I have done interviews on which I have applied narrative analysis.

Even though unhealthy habits, drinking, smoking and overeating, are among the most expensive burdens for the health system, much research is still needed to understand how individuals form them, how do they correlate between them and what impacts do they have in labor productivity. The first paper in this thesis fills in the gap of un- derstanding whether individuals substitute among habits by exploring the effect that quitting smoking has on obesity. The second paper analyze the impact that the business cycle, that is, unemployment rate and income per capita have on drinking participation and alcohol consumption. To overcome the lack of a true longitudinal panel which would prevent us from obtaining unbiased estimates in these two first papers, we use cohort analysis methodology to control for unobservables, while instrumenting the habit deci- sion and introducing dynamics into the estimation equation. The third paper focuses on the effects of smoking over labor productivity. Here we exploit many outcomes that are potentially correlated with individual labor productivity using a longitudinal panel and instrumenting the smoking decision. The three papers make use of a dataset on US regulations regarding tobacco use, which was self developed from the compilation of the different laws enacted by the states. / Tot i que els hàbits no saludables, com poden ser beure, fumar o menjar en excés, són algunes de les càrregues més cares per al sistema de salut, encara és necessari molt més recerca per entendre com els individus formen els hàbits, com aquestes es correlacionen entre si, i quins efectes tenen per a la productivitat. El primer document busca comprendre si els individus substitueixen uns hàbits per altres, en particular, analitza l'impacte que deixar de fumar té sobre l'obesitat. El segon article analitza l'impacte que té el cicle econòmic, és a dir, la taxa d'atur i l'ingrés per càpita, sobre la decisió de beure i sobre el volum d'alcohol consumit. Per superar la manca d'un veritable panell longitudinal que impedeix obtenir estimacions no esbiaixades, en aquests dos primers articles s'ha utilitzat la metodologia de l'anàlisi de cohortes per a poder controlar d'aquesta manera per a les característiques no observables, en particular les preferencies, al mateix temps que s'ha instrumentat la decisió de l'hàbit i s'ha introduït dinàmica en l'equació d'estimació. El tercer document se centra en els efectes del tabaquisme sobre la productivitat laboral. Aquí s'exploren moltes variables que potencialment estan correlacionades amb la productivitat del treball, utilitzant un panell longitudinal i instrumentant la decisió de fumar. Els tres documents fan servir un conjunt de dades sobre reglaments pel que fa a l'ús del tabac als Estats Units.

The aetiology of Parkinson's disease (PD) is still unclear. Research findings suggest that both environmental and genetic factors may contribute to its development. The interactions between genes and the environment might exist and play a key role. Cigarette smoking was found to be one of the few factors exhibiting a protective effect. If chemical compounds found in cigarette smoke influence PD risk, the difference in the ability of certain individuals in metabolising these substances might alter their susceptibility to the risk of developing PD. Many metabolic enzyme genes exhibit polymorphic traits with alteration of gene function. These might be associated with an altered susceptibility of individuals to PD. Few studies have examined the hypothesis that metabolic enzyme gene polymorphisms might modulate the effect of smoking on PD risk. However, it is crucial to consider these potential interactions when we try to elucidate the aetiology of PD. Even if each factor only contributes a slight variation and influences a small portion of the whole population, non-linear and unpredictable interactions may account for a high proportion of the aetiological fraction. Previous studies have not been strictly designed to examine the interactions between smoking and metabolic enzyme genetic polymorphisms. These studies have not been able to elucidate the extent of the interaction. Therefore, this PhD project attempted to examine whether genetic factors, operating in the phase one and phase two metabolic pathways, interact with smoking to influence the development of PD. This is the first genetic epidemiological study of PD specifically addressing this issue. The research aids in further understanding the aetiology of PD and may be useful for identifying people at higher risk. A case-only design was chosen for this project for two reasons: first, PD is a relatively rare disease and the case-only design is much more efficient at detecting gene-environment interactions; second, the PD cases for the project were recruited over the past few years and represent a prevalence series, for which an appropriate comparison group for the cases is difficult to identify and recruit. In a case-only study, only cases are used to investigate the multiplicative effects of the exposures and susceptible genotypes of interest, while non-case subjects (traditionally controls) are solely used to test the independence between the exposure and the susceptible genotype. Therefore, this approach avoids the challenges of control selection, a major limitation inherent in the case-control approach. This thesis comprised of three independent studies: the first study investigated the interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in PD; the second study examined the interactions between genetic polymorphisms of CYP2E1 and smoking in PD; and the third study examined the interactions between genetic polymorphisms of CYP2D6 and smoking in PD. The first two studies recruited 400 white Caucasian PD cases from both hospital wards and private neurology clinics (230 men and 170 women). The third study further included 142 white Caucasian PD cases newly recruited from the same sources (542 in total, 321 men, and 221 women). The mean age of cases was 67 years with the average onset age at 60 years. GSTM1, GSTP1, GSTT1, GSTZ1 AND CYP2E1 genotyping processes were performed using protocols previously published with minor modification, whereas CYP2D6 genotyping methods were mainly developed by me with assistance from associate supervisor Dr. George Mellick. Reliability and validity of the PCR and RFLP methods were assessed through re-conducting the genotype assays using at least a 10% sample of our DNA samples. The results for all re-assessments were 100% concordant. Crude bivariate analyses were adjusted for potential confounding effects of the variables, including age at onset, gender, family history of PD and pesticide exposures. Among our unaffected, aged subjects (mean age: 63.9 years, sd: 11.4 years), the genotype frequencies at each locus were similar to those reported in other Caucasian populations. The first study showed that the proportion of carriers of the GSTP1-114Val allele (mutant) increased with increasing smoking dose from 0 to > 30 pack-years. Homozygotes of the 114Ala allele (wild-type) decreased with increasing smoking dose (trend test: p=0.02). This trend existed both in male and female cases. This dose-effect relationship was most significant in the group of cases with late-onset PD (i.e., age at onset > 55 years) with the ORicase-only values of 1.88 (95%CI: 0.65-5.48) and 2.63 (95%CI: 1.07-6.49) for > 0-10 and > 10 pack-years, respectively. No similar trend was found among our unaffected, aged subjects (p=0.42). Haplotype analyses revealed significant differences for GSTP1 haplotypes between smoking and non-smoking PD cases (ORicase-only for *C haplotype=2.00 (95%CI: 1.11-3.60), p=0.03). In this case, smoking-exposed PD cases were more likely to posses the *C haplotype defined by A to G base-pair transition at nucleotide +313 and C to T base-pair transition at nucleotide +341 (at amino acid level, valine at both positions 105 and 114). The second study found no difference in CYP2E1 genotype frequencies between PD cases who ever smoked compared to those who never smoked (odds ratio for interaction (ORi) = 1.00 (95% CI: 0.39-2.51, p=0.99)). No CYP2E1 gene-smoking interactions were detected in relation to age at onset of PD. The third study found that among cases without regular pesticide exposures, CYP2D6 PMs who smoked more than 5 pack-years had a later mean age at disease onset (68.6 years) than those with extensive metaboliser phenotypes (EMs) (61.1 years, p=0.02) and non-smokers (60.5 years, p=0.01). Analysis of aged subjects without PD confirmed that neither smoking status nor CYP2D6 PM status was associated with age itself. Our data suggest: 1. smoking exposure is independent of GSTM1, P1, T1, Z1 and CYP2E1 genotypes; 2. smoking may be, to some extent, associated with CYP2D6 genotypes; 3. there are no multiplicative interactive effects linking smoking and GSTM1, T1, Z1 or CYP2E1 genotypes with the risk for PD; 4. there is a multiplicative interactive effect between smoking and GSTP1 haplotype - particularly for genotypes carrying the 114Val allele; and 5. there is a multiplicative interactive effect between smoking and CYP2D6 PMs - particularly for people who ever smoked cigarettes more than 5 pack-years. In general, this thesis provides a model for exploring the gene-smoking interactions in PD. Further studies need to consider the recruitment of a large number of population-based and randomly-selected samples and to pay more attention to measurement of environmental exposures. Further studies also need to examine simultaneously the impact of smoking, pesticide exposures and other potential risk factors on PD. These studies will build evidence for interactions contributing to this common neurological movement disorder.

This thesis was funded by the Department of Human Services (South Australia) to test the acceptability of nicotine patches to pregnant women and to assess the safety of nicotine patches for pregnant women, at least in terms of overall exposure to nicotine. The study was conducted in the antenatal clinics at the Women's and Children's Hospital, Adelaide and was a pilot for a planned larger study. If the pilot indicated that the nicotine patches could be used safely by this group of women, the larger study would examine the effectivemess of patches in a smoking cessation program. Four focus groups, three with pregnant women and one with their care providers, were used to elucidate issues for pregnant women related to smoking and the use of nicotine patches to aid cessation.

Exhaled breath condensate (EBC) is a non-invasive method of investigating airway inflammation associated with nitric oxide (NO) and the metabolites nitrite/nitrates (NOx) in diseases such as chronic obstructive pulmonary disease (COPD), but some of the variables affecting the results are unknown. It was hypothesised that 1) EBC would be influenced by lung volumes and the type of EBC collection device; 2) fractional exhaled NO (FENO) and EBC NOx in COPD patients would be altered by smoking and glucocorticosteroids (GCS); 3) cigarette smoke could contribute to the EBC NOx concentration while it may also decrease FENO indirectly by converting airway NO to NOx. It was found that EBC volume was significantly correlated with both tidal volume and minute volume. Comparing four EBC collection devices demonstrated greater efficiency with the ECoScreen?? than siliconised glass tubes or RTube?? but it gave factitiously high NOx levels. Total EBC protein levels over a 10-minute collection were significantly higher using the ECoScreen?? than either glass or RTube?? devices. A cross-sectional study of 96 COPD patients and 80 age-matched control subjects demonstrated that FENO levels in COPD patients were significantly higher than normal subjects when comparing either the combined groups or appropriate two subgroups: ex-smokers and smokers. GCS treatment demonstrated no significant effect on either FENO levels or EBC NOx, but EBC NOx was elevated in smokers. In vitro, cigarette smoke extract (CSE) induced significantly higher NOx and asymmetric dimethylarginine (ADMA) levels in A549 cells when compared with control media. The anti-oxidant, NAC pre-treatment partially reversed the elevated NOx levels but not the ADMA levels. This thesis is the first to report FENO and EBC NOx in COPD patients in an appropriate sample size to be able to evaluate each subgroup, and the increased EBC NOx levels found in smokers in vivo was consistent with the elevated NOx level in response to CSE observed in vitro. These data indicate that smoking-related airway inflammation and activation of the NO pathway are complex with both an increase in ADMA, NO, NOx and may be regulated by oxidative stress rather than the nitric oxide synthase (NOS) pathway.

Bibliography: leaves 215-236 / xiii, 238, [78] leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1988