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.

Cellular inhibitor of apoptosis-2 is a critical regulator of apoptosis in airway epithelial cells treated with asthma-related inflammatory cytokines.

Aberrant apoptosis of airway epithelial cells (AECs) is a disease contributing feature in the airways of asthmatics. The proinflammatory cytokines tumor necrosis factor α (TNFα) and interferon γ (IFNγ) are increased in asthma and have been shown to contribute to apoptosis at the airways. In the present study, we investigated the role of the inhibitor of apoptosis protein (IAP) family in primary AECs exposed to TNFα and IFNγ. IAPs are potent regulators of caspase activity elicited by the intrinsic and extrinsic apoptosis pathways. However, while caspase-mediated apoptosis was observed in AECs exposed to doxorubicin, it was not observed after cytokine treatment. Instead, AECs exhibited proapoptotic changes evidenced by an increased Bax:Bcl2 transcript ratio and partial processing of procaspase-3. Examination by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western analysis showed that proapoptotic changes were associated with a time- and dose-dependent induction of cellular IAP-2 (cIAP2), potentiated primarily by IFNγ. The abundance of the IAP antagonists X-linked IAP-associated factor 1 (XAF1) and second mitochondria-derived activator of caspases did not change, although a moderate nuclear redistribution was observed for XAF1, which was also observed for cIAP2. Small interfering RNA (siRNA)-mediated depletion of cIAP2 from AECs leads to caspase-3 activation and poly (ADP-ribose) polymerase cleavage, but this required extended cytokine exposure to produce a concomitant decrease in cIAP1 and Bcl2. These results indicate that AECs possess endogenous mechanisms making them highly resistant to apoptosis due to asthma-related inflammatory cytokines, and the activity of cIAP2 plays an important role in this protection.

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.

Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1ß and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1ß and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1ß and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1ß and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis.

Long-acting ß-agonists in asthma management: what is the current status?

Large surveillance studies or phase IV clinical studies of long-acting ß-agonists (LABA) compared with placebo in asthma patients using variable (from nil to regular) doses of inhaled corticosteroids (ICS) have raised the issue of mortality risk in patients with asthma taking regular LABA. There have been a number of meta-analyses and systematic reviews that have examined the risk of LABA in asthma patients, and the general conclusion is that LABA added to ICS reduces asthma-related hospitalizations compared with ICS alone and there is no statistical increase in mortality. However, LABA without ICS do increase mortality risk in asthma. All reviews and analyses show a greater number of LABA deaths, but not all are statistically significant. A recent meta-analysis found LABA with concomitant ICS had a higher mortality rate in asthma than ICS alone. The flaw in the study is the higher doses of ICS in the control arms, but the implicit message remains: the essential need for enough ICS to control airway inflammation. We suggest that the pragmatic solution is to have LABA only available in the same device as ICS for asthma treatment. We do not think that a study comparing the safety of LABA plus ICS versus ICS alone in asthma is necessary. If such a study is conducted, the measurement of morbidity from increased doses of ICS is an essential design consideration. Furthermore, the critical focus in asthma management should not be forgotten - education of health professionals and the community of the critical role of ICS, and the need for good communication between health professionals and the asthma patient to facilitate good asthma control. The same arguments apply to the asthma-with-chronic obstructive pulmonary disease overlap syndrome in older patients. There is an urgent need to provide medical practitioners with the capability to diagnose the overlap syndrome.

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.

Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation.

The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

Systematic care for asthma in Australian general practice: a randomised controlled trial.

OBJECTIVE: To evaluate whether systematic asthma care involving a register-recall system, postcard prompts for review, and education for general practitioners and staff in Australian general practice improves the quality of care and health outcomes for adult patients with moderate to severe asthma. DESIGN AND SETTING: Cluster randomised controlled trial in 40 general practices in urban and rural South Australia and New South Wales over the 2 years 2004 and 2005; practices were randomly allocated to the intervention or control group. PARTICIPANTS: 565 adult patients of these randomly allocated practices who had doctor-diagnosed moderate to severe asthma and were taking inhaled corticosteroids. MAIN OUTCOME MEASURES: Clinical asthma indicators, quality of care, acceptability of the intervention to patients, quality of life, and asthma self-management skills at baseline, 6 months and 12 months. RESULTS: Although 46% of patients in the intervention group practices responded to the postcard prompts, only 32% actually attended for their asthma review. At 12 months, there was a statistically significant difference in provision of written asthma action plans (rate ratio, 1.9; 95% CI, 1.0-3.5; P = 0.04) for intervention group patients compared with control group patients; there was no significant difference in other indicators. CONCLUSION: We found little objective evidence of improvement in patient management and outcomes resulting from a systematic model of asthma care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12605000091606.

Global Initiative for Chronic Obstructive Lung Disease stage 0 is associated with excess FEV(1) decline in a representative population sample.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline removed stage 0 (chronic cough and sputum without airflow obstruction, GOLD-0) because of poor prognostic value. Preventative intervention may be relevant for those with chronic symptoms; therefore, we assessed the stability, morbidity, and FEV(1) decline associated with GOLD stage 0 in a representative adult population cohort. METHODS: Baseline (n = 4,060) and follow-up (n = 3,206, mean 3.5 years) clinic assessment of the North West Adelaide Health Study included postbronchodilator spirometry, anthropometry, and measures of doctor-diagnosed asthma, respiratory symptoms, smoking status, quality of life, and depression. RESULTS: Baseline GOLD-0 prevalence was 17.0% (n = 584). At follow-up (n = 420), 39.8% remained stable, 1.4% progressed to GOLD stages 1 to 2, and 58.8% resolved to no symptoms. Persistent GOLD-0 at follow-up was associated with persistent smoking (men: odds ratio [OR] = 11.9, 95% CI, 6.4-22.1; women: OR = 4.0, 95% CI, 2.1-7.4), and depressive symptoms (men: OR = 3.8, 95% CI, 1.9-7.6; women: OR = 3.2, 95% CI, 1.7-5.9), with highest quartile of FEV(1) decline (mL) per year (OR = 2.1, 95% CI, 1.2-3.7) and the metabolic syndrome (OR = 1.7, 95% CI, 1.01-3.0) in men, and with older age in women. These associations generally held in smokers and never-smokers. Resolving GOLD-0 was associated with smoking cessation (OR = 13.7; 95% CI, 4.6-40.1), FEV(1) decline (mL) per year below the median (OR = 2.0; 95% CI, 1.1-3.5), normal BMI, and younger age groups. Sensitivity analyses based on the presence of sputum did not change the observed associations. CONCLUSION: Persistent GOLD-0 identified people with physical and psychologic morbidity in both smokers and nonsmokers. Identification of those with persistent respiratory symptoms is therefore important. Excess FEV(1) decline in men suggests GOLD-0 may identify a group at risk to progress to COPD over time.

Depression and obesity in adults with asthma: multiple comorbidities and management issues.

OBJECTIVE: To examine the comparative prevalence and distribution of obesity and psychological disturbance in the asthma and non-asthma populations, and to determine how these comorbidities are associated with physical functioning. DESIGN, SETTING AND PARTICIPANTS: A South Australian population-representative study of 3175 adults who provided data on asthma, psychological morbidity, physical functioning, and body mass index. Bivariate and multivariate analyses identified how these comorbidities were distributed in asthma and non-asthma subpopulations, and the variance in physical functioning that they explained. MAIN OUTCOME MEASURES: Rates of obesity and psychological morbidity, and physical functioning scores in asthma and non-asthma populations. RESULTS: Men and women in the asthma population had similar prevalences of obesity (35.3% v 33.6%) and psychological morbidity (29.5% v 29.4%). When compared with non-asthma controls, both comorbidities were significantly higher only in men with asthma. The prevalence of psychological morbidity within different weight categories in the asthma population compared with non-asthma weight-category controls varied by sex. Physical functioning was lower in the asthma population than the non-asthma population (46.6 [95% CI, 45.9-47.3] v 48.8 [95% CI, 47.8-50.0]; P < 0.001), and psychological morbidity explained 22% of this variance. CONCLUSIONS: Psychological morbidity and obesity are common in people with asthma. The sex-specific variation in psychological morbidity across weight categories suggests that future studies of psychological morbidity in groups with asthma should adopt designs that consider sex-specific controls rather than comparisons between the sexes.

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.

Associations of physical and mental health problems with chronic cough in a representative population cohort.

BACKGROUND: Although chronic cough is a common problem in clinical practice, data on the prevalence and characteristics of cough in the general population are scarce. Our aim was to determine the prevalence of chronic cough that is not associated with diagnosed respiratory conditions and examine the impact on health status and psychological health, in a representative adult population cohort METHODS: North West Adelaide Health Study (n stage 1 = 4060, stage 2 = 3160) is a representative population adult cohort. Clinical assessment included spirometry, anthropometry and skin tests. Questionnaires assessed demographics, lifestyle risk factors, quality of life, mental health and respiratory symptoms, doctor diagnosed conditions and medication use. RESULTS: Of the 3355 people without identified lung disease at baseline, 18.2% reported chronic cough. In multiple logistic regression models, at follow-up, dry chronic cough without sputum production was significantly more common in males (OR 1.5, 95% CI 1.1, 1.9), current smokers (OR 4.9, 95% CI 3.4, 7.2), obesity (OR 1.9, 95% CI 1.3, 2.9), use of ACE inhibitors (OR 1.8, 95% CI 1.1, 2.9), severe mental health disturbance (OR 2.1, 95% CI 1.4, 3.1) and older age (40-59 years OR 1.7 95% CI 1.2, 2.4; > or = 60 years OR 2.1 95% CI 1.3, 3.5). Among non-smokers only, all cough was significantly more common in men, those with severe mental health disturbance and obesity. CONCLUSIONS: Chronic cough is a major cause of morbidity. Attention to cough is indicated in patients with obesity, psychological symptoms or smokers. Inquiring about cough in those with mental health problems may identify reversible morbidity.

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.

Self-reported adverse events in health care that cause harm: a population-based survey.

OBJECTIVES: To identify the incidence of self-reported harmful adverse events in the health care of community-dwelling adults, and to examine attitudes about safety in the health system. DESIGN: Cross-sectional, population-based survey. PARTICIPANTS AND SETTING: Analysis of data from 3522 adults participating in Stage 2 of the North West Adelaide Health Study, who were surveyed in 2004 and 2005. MAIN OUTCOME MEASURES: Self-reported adverse events causing harm in the past year; attitudes to safety in health care, including adequacy of current measures for preventing adverse events, and the effect of groups like patients themselves, doctors and governments on patient safety. RESULTS: The annual incidence of self-reported harmful adverse events was 4.2%. The main types were medication error (45.5%) and misdiagnosis or wrong treatment (25.6%). Multiple logistic regression showed that self-reported harmful adverse events were more likely in people who had been hospitalised in the past 12 months (odds ratio [OR], 2.5; 95% CI, 1.9-3.4), those who had low annual income (< $12 000), those who completed higher education to the level of Bachelor degree or higher (OR, 3.0; 95% CI, 1.0-9.4), and those who had some level of dissatisfaction with their recent health care; and less likely in those more risk-averse rather than those with a tendency to risk-taking behaviour (OR, 0.6; 95% CI, 0.4-0.9). People were more likely to believe that individual health care professionals had a positive effect on safety than professional groups or government, and that more resources were the key to improving the safety of health care. CONCLUSION: We found an incidence of self-reported harmful adverse events that was significantly lower than that found by a 2002 Australian survey (4.2% v 6.5%; P = 0.009). Better communication to help patients acquire more realistic risk perception may help reduce harm. Better communication could also increase public advocacy for systems improvement in safety to counter persisting community beliefs that individual action alone can redress the situation.

Effects of area deprivation on health risks and outcomes: a multilevel, cross-sectional, Australian population study.

OBJECTIVES: Our aim was to examine the effect of local area socio-economic disadvantage after accounting for individual socio-economic status (SES), and to determine if these differ between various health and risk factor variables. METHODS: The North West Adelaide Health Study (NWAHS) is a biomedical representative population study of adults. The Index of Relative Socio-Economic Disadvantage (IRSD), produced from the Australian Bureau of Statistics (ABS) Census data at the level of Collector Districts (200 dwellings) was used as an indicator of local area disadvantage. Multi-level modeling techniques examined the effects of IRSD level on a variety of health outcomes and risk factors, after accounting for individual socio-economic factors. RESULTS: Significant, independent associations were seen between IRSD and obesity, smoking, and health-related quality of life, with 5 % to 7.2 % of the variance located at the neighborhood level. No independent associations were seen between IRSD and estimated cardiovascular disease risk, diabetes, physical activity, or at-risk alcohol use. CONCLUSIONS: Aggregated area-level characteristics make modest, but significant independent contributions to smoking, obesity and quality of life, but not for other health outcomes.

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.

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.