BIRC3 single nucleotide polymorphism associate with asthma susceptibility and the abundance of eosinophils and neutrophils.

BACKGROUND AND OBJECTIVE: Aberrant apoptosis is a disease susceptibility mechanism relevant for asthma, whereby fragility of the airway epithelium and enhanced survival of inflammatory cells, contributes to its pathogenesis and prolongation. Cellular Inhibitor of Apoptosis Proteins (cIAP) suppress apoptosis, and participate in the immune response. In this study, single nucleotide polymorphisms (SNP) in the BIRC2 (codes cIAP1) and BIRC3 (cIAP2) genes were evaluated for an association with asthma. METHODS: Caucasian asthmatic (n = 203) and control (n = 198) subjects were selected from participants in the North West Adelaide Health Study. SNPs (n = 9) spanning the consecutively positioned BIRC2 and BIRC3 genes, were selected using a haplotype tagging approach. Alleles and haplotype associations were analysed by logistic regression, assuming an additive genetic model, and adjusted for gender and atopy. RESULTS: The frequency of the minor allele for the BIRC3 SNP rs3460 was significantly lower in asthmatics compared to the control cases (P = 0.046). BIRC3 SNPs rs7928663 and rs7127583 associated with a reduction in eosinophil and neutrophil abundance when assessed across the study population (multivariate P values = 0.002, and 0.005, respectively). Further, the frequency of a haplotype tagged by rs3460, rs7928663 and rs7127583 was reduced in the asthma sub group (P = 0.05), while the presence of the major allele for rs7928663 associated with an increased load of circulating eosinophils and neutrophils (multivariate P value = 0.001). CONCLUSIONS: Polymorphisms in the BIRC3 gene, but not BIRC2, are associated with a protective effect with regards to asthma susceptibility, and a reduced load of inflammatory cells.

X-linked inhibitor of apoptosis single nucleotide polymorphisms and copy number variation are not risk factors for asthma.

BACKGROUND AND OBJECTIVE: Aberrant apoptosis in asthma contributes to airway inflammation. Early apoptosis and fragility of airway epithelial cells and delayed apoptosis of inflammatory lymphocytes can cooperate to increase airway inflammation. In this study, single nucleotide polymorphisms (SNPs) and copy number variation (CNV) in the Baculoviral inhibitor of apoptosis protein repeat-containing 4 (BIRC4) gene (which encodes X-linked inhibitor of apoptosis protein) were evaluated for associations with asthma. METHODS: Asthma cases (n = 203) were identified from Caucasian cohort participants in the North West Adelaide Health Study and matched with 198 controls. Asthma status was defined using self-report of doctor-diagnosed asthma, in conjunction with spirometry and bronchodilator response. Seven SNPs, which spanned the entire BIRC4 gene, were selected for the study on the basis of a haplotype tagging approach. SNPs genotyping was performed on the SEQUENOM MassARRAY iPLEX Gold platform, and genotyping success rate was > 98%. BIRC4 gene CNV was measured using a duplex Taqman qPCR assay, with RNAseP as the reference gene. Alleles and haplotype associations were analysed by logistic regression, assuming an additive genetic model, and adjusted for gender and atopy. RESULTS: BIRC4 gene copy number was determined entirely by gender. All SNPs were in Hardy-Weinberg equilibrium for both case and control females. BIRC4 allele and haplotype frequencies were comparable between asthma cases and controls. CONCLUSIONS: There is no evidence of CNV in BIRC4, and BIRC4 is not a susceptibility gene for asthma.

Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms.

BACKGROUND: This study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB). METHODS: A random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults (≥18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations. RESULTS: The prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 - 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12 mL and 20 mL in FEV1 and FVC respectively in men, and 4 mL and 7 mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women. CONCLUSIONS: In this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may contribute up to one quarter of this association.

Sputum zinc concentration and clinical outcome in older asthmatics.

BACKGROUND AND OBJECTIVE: Mouse models of asthma show that zinc deficiency is associated with airway inflammation (AI), which is attenuated by zinc supplements. Whether zinc has a similar role in the human airway remains controversial, with studies demonstrating both high and low plasma zinc concentrations [Zn] in asthmatic patients compared with control subjects. This variability may reflect the inability of plasma measurements to accurately assess airway zinc levels. Examination of induced sputum is an established technique for measuring AI and mediators of inflammation. Recent advances allow measurement of the rapidly exchangeable (labile) and total zinc pools in sputum. The aims of this study were to measure labile and total [Zn] in sputum and plasma of subjects with or without asthma, and second to correlate [Zn] with symptoms, asthma severity, lung function (FEV(1)) and airway hyper-responsiveness. METHODS: A total of 163 subjects (114 with asthma) completed a single visit for sputum induction and a blood test. Labile and total [Zn] were measured by Zinquin fluorescence and atomic absorption spectrophotometry. RESULTS: The mean (SD) age of subjects with and without asthma was 55 (14) and 57 (14) years, respectively. Baseline FEV(1) was significantly lower in subjects with asthma (94.2 (16)%) than in those without asthma (103 (16.6)%). Sputum total and labile [Zn] were lower in subjects with asthma compared with control subjects, with median (interquartile range) values of 31.8 (117) versus 50 (188.5), P = 0.02 and 0 (48) versus 26 (84.5) µg/L, P = 0.05, respectively. Increased frequency of wheeze, as well as asthma severity and reduced FEV(1), was associated with significantly lower labile sputum [Zn]. CONCLUSIONS: These findings suggest that sputum [Zn] reflect clinical outcomes and underlying AI, suggesting a potential role for zinc as a biomarker in asthma.

Gender differences in asthma prevalence: variations with socioeconomic disadvantage.

BACKGROUND AND OBJECTIVE: Socioeconomic inequalities in health have been shown to vary for different diseases and by gender. This study aimed to examine gender differences in associations between asthma and socioeconomic disadvantage. METHODS: Socioeconomic variables were assessed among men and women in the North West Adelaide Health Study, a representative population cohort (n = 4060) aged 18 years and over in metropolitan South Australia. Asthma was determined from spirometry and self-reported doctor diagnosis. RESULTS: The prevalence of asthma was 12.0% (95% CI: 11.1-13.1), and was significantly higher among women (13.5%) than men (10.5%). For participants aged 18-64 years a higher prevalence of asthma was associated with an education level of secondary school or lower, or not being in the paid labour force among men, and with a gross annual household income of $20,000 or less among women. Among socioeconomically advantaged groups, the prevalence of asthma was significantly higher among women than men. CONCLUSIONS: Socioeconomic disadvantage was associated with higher asthma prevalence, although this varied by gender depending on the indicator of socioeconomic position used. Men with low education or those not employed in the paid labour force had higher asthma prevalence than more socioeconomically advantaged men. Women with low income had higher asthma prevalence than those with higher income. Among all socioeconomically advantaged groups, and also the low-income group, women experienced a higher prevalence of asthma than men.

Cardiovascular disease risk associated with asthma and respiratory morbidity might be mediated by short-acting beta2-agonists.

BACKGROUND: Studies examining the asthma-related risks of cardiovascular disease (CVD) events have generally used selected samples or did not control for the effects of beta(2)-agonist use, itself associated with CVD events. OBJECTIVES: We assessed the relationship between incident CVD/stroke and asthma and the effect of atopy while controlling for beta(2)-agonist use in a representative adult population cohort free of CVD at baseline. METHODS: The North West Adelaide Health Study (stage 1, n = 3812; stage 2, n = 3113) assessed spirometry, anthropometry, atopy, blood pressure, and lipid levels. Questionnaires assessed doctor-diagnosed asthma and CVD (myocardial infarction and angina)/stroke, smoking status, and demographics. Asthma was defined by self-report or FEV(1) reversibility. Current short- and long-acting beta(2)-agonist use was identified at follow-up. RESULTS: Results are expressed as odds ratios (ORs) and 95% CIs. By using multivariable logistic regression, after adjustment for risk factors, in female subjects incident CVD/stroke events were associated with asthma (OR, 3.24; 95% CI, 1.55-6.78), with no effect modification by atopy (P for interaction = .61), and with as-required short-acting beta(2)-agonist use (OR, 2.66; 95% CI, 1.06-6.61). In male subjects events were associated with daily cough/sputum (OR, 1.92; 95% CI, 1.05-3.50) and FEV(1) of less than 80% of predicted value but an FEV(1)/forced vital capacity ratio of greater than 0.70 (OR, 2.15; 95% CI, 0.91-5.09; P = .08). Although few CVD/stroke events occurred in male subjects with asthma, a significant interaction with atopic status was found (P = .05). CONCLUSIONS: Studies are required to elucidate how asthma exposes older women to excess macrovascular risk and prospectively determine the short-acting beta(2)-agonist-related risk in persons without existing CVD. CVD risk in relation to atopic status of asthma also requires further investigation.

Cholesterol-lowering therapy and the Australian Pharmaceutical Benefits Scheme: a population study.

OBJECTIVE: The Australian Pharmaceutical Benefits Scheme (PBS) expanded the criteria for eligibility for subsidised lipid-lowering therapy (LLT) in 2006. The aim of this study was to determine the use of LLT in a representative Australian population in relation to cardiovascular disease (CVD) risk, and the effectiveness of the therapy in meeting target levels. DESIGN: Cross-sectional biomedical study with telephone interviews, questionnaires, clinical measurements, and PBS dispensing data. SUBJECTS: Representative population sample of 4060 urban adults aged > or = 18 years attending for the biomedical examination in 2001. RESULTS: Of the 406 who qualified for PBS-subsidised LLT at that time, only 88 (21.5%) were actually on LLT. National Heart Foundation of Australia (NHF) recommended low-density lipoprotein cholesterol (LDL-C) levels of < 2.5 mmol/L were recorded in only 13% (528) of the population, and in 46.8% of those on LLT. Of those on LLT, 76% had total cholesterol < 5.5 mmol/L, but over 80% had total cholesterol levels above NHF-recommended levels of 4.0 mmol/L. Of the 842 classified at the highest CVD risk, only 26% were using LLT. Those aged > 60 years and on low incomes were significantly more likely to use LLT. The new PBS criteria will expand eligibility to include nearly 20% of adults. CONCLUSIONS: The majority of people at high risk of CVD were not receiving LLT, and LLT is not being used to its full effectiveness. People with low incomes or on government benefits or pensions were not less likely to use LLT than others under the PBS scheme. Whether higher copayments for those on low incomes who do not qualify for concessional payments is a significant barrier to LLT use needs further research.

Medicare-related service use and costs among people with diagnosed and undiagnosed diabetes and respiratory conditions.

OBJECTIVE: To compare Medicare-related costs and service utilisation of people with diagnosed diabetes, asthma or chronic obstructive pulmonary disease (COPD) to those who were previously undiagnosed, and those without these conditions. DESIGN, SETTING AND PARTICIPANTS: Representative cross-sectional study of people (18+ years) living in the north-west area of Adelaide. Participants were recruited by telephone interviews. Biomedical and self-report data for 2352 participants were linked to Medicare Australia Medicare Benefits Schedule (MBS) data from 1997 to 2002. MAIN OUTCOME MEASURES: Mean number and cost (benefit paid) of MBS services for people with diagnosed and previously undiagnosed diabetes, asthma, and COPD, and those without these conditions. RESULTS: Mean (+/- SD) MBS costs were significantly greater for people diagnosed with diabetes ($4205 +/- 2596), asthma ($3307 +/- 2542), or COPD ($3779 +/- 2529) than for those without these conditions. MBS costs for people with asthma or COPD that had not yet been diagnosed were also significantly higher than for those without these conditions, although this was inconsistent across financial years. CONCLUSIONS: Diabetes, asthma, and COPD are costly conditions in terms of health service use. Costs associated with undiagnosed asthma and COPD are similar to their diagnosed states. Prevention of progression along each chronic disease continuum is likely to reduce costs.

Zinc metabolism in airway epithelium and airway inflammation: basic mechanisms and clinical targets. A review.

In addition to basic housekeeping roles in metalloenzymes and transcription factors, dietary zinc (Zn) is an important immunoregulatory agent, growth cofactor, and cytoprotectant with anti-oxidant, anti-apoptotic, and anti-inflammatory roles. These properties of Zn are of particular importance in maintaining homeostasis of epithelial tissues which are at the front line of defense. This review is about the role of Zn in airway epithelium (AE). The first part focuses on the cellular biology of Zn, and what is known about its distribution and function in AE. The second part of the review considers evidence for altered Zn metabolism in asthma and other chronic diseases of airway inflammation. Important issues arise from a potential therapeutic perspective as to the optimal ways to monitor circulating and epithelial Zn levels in patients and the most effective means of supplementing these levels.

Coexistent chronic conditions and asthma quality of life: a population-based study.

OBJECTIVE: Reports of the prevalence and impact of comorbid conditions among people with asthma have been limited to certain population groups or convenience samples. Our aim was to examine the prevalence of major comorbidity in asthma and associations with quality of life and functional status in the general population. STUDY DESIGN/SETTING: The WANTS Health and Well-being Survey is a cross-sectional representative population household telephone interview survey in three Australian states. PARTICIPANTS: Representative sample of noninstitutionalized adults in three Australian states. MEASUREMENT AND RESULTS: From the available sample of 10,080 patients, 7,619 interviews were completed (participation rate, 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). People with asthma were more likely to report one of the selected comorbid conditions: diabetes, arthritis, heart disease, stroke, cancer, osteoporosis (adjusted odds ratio, 1.9; 95% confidence interval, 1.5 to 2.2). Among people with asthma, there were statistically and clinically significant decreases in usual activity levels and in Short Form-12 physical component summary scores when another chronic condition was also present. For those with any of the chronic conditions, the additional presence of asthma was associated with significant further impairment in quality of life in those aged > 35 years but not in younger adults. CONCLUSION: The significant reduction in quality of life associated with comorbidity in asthma has implications for disease management and organization of care, as well as for the design and external validity of single-disease clinical trials.

The North West Adelaide Health Study: detailed methods and baseline segmentation of a cohort for selected chronic diseases.

The North West Adelaide Health Study is a population-based biomedical cohort study investigating the prevalence of a number of chronic conditions and health-related risk factors along a continuum. This methodology may assist with evidence-based decisions for health policy makers and planners, and inform health professionals who are involved in chronic disease prevention and management, by providing a better description of people at risk of developing or already diagnosed with selected chronic conditions for more accurate targeting groups for health gain and improved health outcomes. Longitudinal data will provide information on progression of chronic conditions and allow description of those who move forward and back along the continuum over time. Detailed methods are provided regarding the random recruitment and examination of a representative sample of participants (n = 4060), including the rationale for various processes and valuable lessons learnt. Self-reported and biomedical data were obtained on risk factors (smoking, alcohol consumption, physical activity, family history, body mass index, blood pressure, cholesterol) and chronic conditions (asthma, chronic obstructive pulmonary disease, diabetes) to classify participants according to their status along a continuum. Segmenting this population sample along a continuum showed that 71.5% had at least one risk factor for developing asthma, chronic obstructive pulmonary disease or diabetes. Almost one-fifth (18.8%) had been previously diagnosed with at least one of these chronic conditions, and an additional 3.9% had at least one of these conditions but had not been diagnosed. This paper provides a novel opportunity to examine how a cohort study was born. It presents detailed methodology behind the selection, recruitment and examination of a cohort and how participants with selected chronic conditions can be segmented along a continuum that may assist with health promotion and health services planning.

A cohort study of indoor nitrogen dioxide and house dust mite exposure in asthmatic children.

OBJECTIVE: The purpose of this study was to investigate dose-response relationships between asthma symptoms and indoor nitrogen dioxide (NO2) and house dust mite allergen (HDM) in children. METHODS: Asthmatic children from 18 primary schools in Adelaide, Australia, kept a daily symptoms diary over 12 weeks. Home and classroom NO2 levels were measured repeatedly in winter 2000. HDM levels were obtained from beds. Lung function tests were performed at the beginning and at the end of the study period. RESULTS: Data on exposure and respiratory outcomes were gathered for 174 children. For school exposure, the estimated relative symptom rate (RR) for a 10-ppb increase in NO2 for difficulty breathing during the day was 1.09 (95% confidence interval [CI] = 1.03-1.15), at night 1.11 (95% CI = 1.05-1.18), and for chest tightness at night 1.12 (95% CI = 1.07-1.17). Significant symptom rate increases were also found for kitchen NO2 exposure. This was supported by a negative dose-response relationship between percentage predicted forced expiratory volume in 1 second and NO2 (-0.39%; 95% CI = -0.76 to -0.02) for kitchen exposure. Significant threshold effects using a 10-microg/g cutoff point for HDM exposure were established in the sensitized children for nighttime wheeze (RR = 3.62, 95% CI = 1.49-8.77), daytime cough (RR = 1.64, 95% CI = 1.14-2.36), and daytime asthma attack (RR = 1.95, 95% CI = 1.06-3.60). CONCLUSION: This study has established reliable risk estimates for exacerbations of asthma symptoms in children based on dose-response investigations of indoor NO2 and HDM.

How valid are self-reported height and weight? A comparison between CATI self-report and clinic measurements using a large cohort study.

OBJECTIVE: To examine the relationship between self-reported and clinical measurements for height and weight in adults aged 18 years and over and to determine the bias associated with using household telephone surveys. METHOD: A representative population sample of adults aged 18 years and over living in the north-west region of Adelaide (n = 1,537) were recruited to the biomedical cohort study in 2002/03. A computer-assisted telephone interviewing (CATI) system was used to collect self-reported height and weight. Clinical measures were obtained when the cohort study participants attended a clinic for biomedical tests. RESULT: Adults over-estimated their height (by 1.4 cm) and under-estimated their weight (by 1.7 kg). Using the self-report figures the prevalence of overweight/ obese was 56.0% but this prevalence estimate increased to 65.3% when clinical measurements were used. The discrepancy in self-reported height and weight is partly explained by 1) a rounding effect (rounding height and weight to the nearest 0 or 5) and 2) older persons (65+ years) considerably over-estimating their height. CONCLUSION: Self-report is important in monitoring overweight and obesity; however, it must be recognised that prevalence estimates obtained are likely to understate the problem. IMPLICATIONS: The public health focus on obesity is warranted, but self-report estimates, commonly used to highlight the obesity epidemic, are likely to be underestimations. Self-report would be a more reliable measure if people did not round their measurements and if older persons more accurately knew their height.

Do people with risky behaviours participate in biomedical cohort studies?

BACKGROUND: Analysis was undertaken on data from randomly selected participants of a bio-medical cohort study to assess representativeness. The research hypotheses was that there was no difference in participation and non-participations in terms of health-related indicators (smoking, alcohol use, body mass index, physical activity, blood pressure and cholesterol readings and overall health status) and selected socio-demographics (age, sex, area of residence, education level, marital status and work status). METHODS: Randomly selected adults were recruited into a bio-medical representative cohort study based in the north western suburbs of the capital of South Australia--Adealide. Comparison data was obtained from cross-sectional surveys of randomly selected adults in the same age range and in the same region. The cohort participants were 4060 randomly selected adults (18+ years). RESULTS: There were no major differences between study participants and the comparison population in terms of current smoking status, body mass index, physical activity, overall health status and proportions with current high blood pressure and cholesterol readings. Significantly more people who reported a medium to very high alcohol risk participated in the study. There were some demographic differences with study participants more likely to be in the middle level of household income and education level. CONCLUSION: People with risky behaviours participated in this health study in the same proportions as people without these risk factors.

Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation.

The epithelium lining the airways is a physical barrier as well as a regulator of physiological and pathological events in the respiratory system. Damage to the epithelium by oxidants released from inflammatory cells is a critical factor in the pathogenesis of airway inflammatory diseases such as bronchial asthma. In these diseases, excessive apoptosis may be a likely mechanism responsible for damage to, and sloughing, of airway epithelial cells. Factors that increase the airway epithelium's resilience to apoptosis are likely to lessen the severity of this disease. One such factor is the dietary metal zinc. A special role for labile intracellular pools of zinc as anti-apoptotic agents in the regulation of the caspases, has emerged over the past two decades. This review focuses on caspase-inhibitory functions of zinc in airway epithelial cells, apparent abnormalities of zinc homeostasis in asthmatics and studies from the authors' laboratory which showed that zinc was strategically localized in the apical cytoplasm of airway epithelium to control caspase-3 activated apoptosis. These findings are discussed in the context of recent data from a murine model of allergic asthma, showing that loss of airway epithelial zinc was accompanied by changes in levels of both procaspase-3 and active caspase-3 and that nutritional zinc deprivation further increased airway epithelial apoptosis. We hypothesize that zinc has a protective role for the airway epithelium against oxyradicals and other noxious agents, with important implications for asthma and other inflammatory diseases where the epithelial barrier is vulnerable and compromised.

Randomized controlled trial of unflued gas heater replacement on respiratory health of asthmatic schoolchildren.

BACKGROUND: Previous studies do not provide a clear picture of the relationship between nitrogen dioxide (NO(2)) exposure and asthma. METHODS: Eighteen schools using unflued gas heating in winter were randomly allocated to either retain their heaters (10 control schools) or to have replacement flued gas or electric heaters installed at the beginning of winter (8 intervention schools). Fortnightly telephone interviews were used to record daily individual asthma symptoms that occurred over 12 weeks (including winter). Lung function and histamine challenge tests were performed at baseline and the end of the study. NO(2) was measured in each school classroom on 9 days and in each household on 3 days spread over the study period. RESULTS: From 199 primary school children that met the eligibility criteria, 45 intervention and 73 control children agreed to participate. Baseline characteristics were similar between groups. Difficulty breathing during the day (Relative Risk [RR] = 0.41; 95% CI: 0.07, 0.98) and night (RR = 0.32; 95% CI: 0.14, 0.69), chest tightness during the day (RR = 0.45; 95% CI: 0.25, 0.81), and daytime asthma attacks (RR = 0.39; 95% CI: 0.17, 0.93) were significantly reduced in the intervention group. Percentage predicted forced expiratory volume in one second (FEV(1)), the concentration of histamine inducing a 20% fall in FEV(1) (PD(20)), and the dose-response slope (DRS) were similar between groups at follow-up. Mean (standard deviation) NO(2) levels were 15.5 (6.6) parts per billion (ppb) and 47.0 (26.8) ppb in the intervention and control schools respectively (P < 0.001). CONCLUSIONS: Asthma symptoms were reduced following a replacement intervention that removed high exposure to NO(2). Such replacement should be considered a public health priority for schools using unflued gas heating during winter.

The health-related quality of life of male and female heavy smokers.

OBJECTIVES: Heavy smokers are a segment of the smoking population who are at increased risk of smoking-related morbidity and least likely to achieve cessation. This study identifies the impact of heavy smoking on quality of life by gender and describes the subpopulation for improved targeting. METHODS: South Australian representative population data (n = 3010) was used to compare the health-related quality of life status of male and female heavy smokers as assessed by the SF-36. RESULTS: Of the smoking population 18% were classified as heavy smokers. There was a clear dose response relationship between amount smoked and deteriorating quality of life for all female smokers. Female heavy smokers were found to be significantly more impaired on all health-related quality of life dimensions, when compared to male heavy smokers. CONCLUSIONS: The association of smoking with impaired quality of life is more marked in females than in males. There is a need to identify female smokers as a distinct target group in smoking cessation initiatives and programs.