OBJECTIVES:To examine changes in asthma prevalence in the context of other population changes between 1990 and 2003, for specific age and sex groups.DESIGN:Cross-sectional survey based on household interviews, repeated annually.SETTING AND PARTICIPANTS:Representative samples of the South Australian population between 1990 and 2003 (around 3000 people per year).MAIN OUTCOME MEASURES:Current prevalence of doctor-diagnosed asthma and other health and demographic variables potentially associated with asthma, and asthma management.RESULTS:Response rate was over 71%. Between 1990 and 2003, asthma prevalence increased significantly, doubling in females (from 7.3% in 1990 to 14.6% in 2003), with a smaller increase in males (from 7.8% to 9.4%). Asthma also increased in all age groups, but the largest relative increases occurred in people aged 55 years and older. Logistic regression analyses showed that obesity was a major predictive variable for every age group studied. The prevalence of asthma morbidity (waking at night and days lost from usual activities because of asthma) among those with asthma showed no significant changes between 1990 and 2003. Asthma action plans (introduced on a population basis in 1992) peaked in their distribution at 42% in 1994, and then declined to half that percentage in 2003. The increase in asthma prevalence occurred at the same time as increases in population prevalence of obesity (10.3% to 18.7%) and diabetes (3.1% to 6.9%), and decline in recent vigorous exercise (42.4% to 32.7%).CONCLUSIONS:The increase in asthma prevalence over a decade was large, but concentrated among specific sex and age groups. The increase accompanied population increases in obesity and diabetes and a decline in vigorous exercise.

The dietary group fib metal zinc (Zn) plays essential housekeeping roles in cellular metabolism and gene expression. It regulates a number of cellular processes including mitosis, apoptosis, secretion and signal transduction as well as critical events in physiological processes as diverse as insulin release, T cell cytokine production, wound healing, vision and neurotransmission. Critical to these processes are the mechanisms that regulate Zn homeostasis in cells and tissues. The proteins that control Zn uptake and compartmentalization are rapidly being identified and characterized. Recently, the first images of sub-cellular pools of Zn in airway epithelium have been obtained. This review discusses what we currently know about Zn in the airways, both in the normal and inflamed states, and then considers how we might target Zn metabolism by developing strategies to monitor and manipulate airway Zn levels in airway disease.

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.

Use of controller asthma medication and possession of asthma action plans remains suboptimal. Our aim was to investigate the association of the propensity of physicians to involve patients in their care (participatory decision-making style) and their asthma management in a representative population sample of 3015 adults. Current doctor-diagnosed asthma was reported by 393 (13.0%). People who rated their doctors as more participatory were significantly more likely to report more regular use of controller medications and possession of a written asthma action plan, but not less asthma morbidity. Possession of a written action plan was associated with more participatory interactions (OR 2.3; 95% CI 1.1-4.7, for upper tertile scores compared to lowest tertile); more severe symptoms (OR 4.8; 95% CI 1.7-13.0), being female (OR 2.2; 95% CI 1.2-4.3), those with higher education, and residence outside the metropolitan area (OR 2.1; 95% CI 1.1-4.0). Increasing patient participation in their own care is associated with better asthma management, independent of asthma symptoms. Longitudinal studies are needed to examine if increasing participation in decisions can also improve asthma outcomes.

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.

Objective: The socioeconomic variables of income, race and employment status have been shown to influence health-related quality of life (HRQL) scores in persons with asthma. However, little is known about the impact of other psychological factors or perceptions of economic hardship on HRQL in asthma, despite the known influence these have on general activity levels and emotional perceptions. The aim of the present study was to assess the relationships between psychological and socioeconomic factors and HRQL and on subsequent changes to HRQL over 12 months.Methodology: Consecutive adult patients with moderate or severe asthma attending outpatient clinics, emergency departments or who were inpatients at two teaching hospitals, completed surveys of clinical status, psychological and socioeconomic variables, and HRQL instruments (SF-36 and Modified Marks Asthma Quality of Life Questionnaire [MAQLQ-M]), at baseline and over 12-months follow-up.Results: Of 343 eligible subjects, survey responses were received from 293 at baseline and 232 at 12-months. Mean age was 42 years (SD 18), 67% were female, 42% had moderate, and 58% severe current asthma clinical status according to the National Asthma Education and Prevention Program guidelines criteria. In random-effects multiple regression models, after adjusting for age, gender, education, income and hospital, significant independent variables associated with each of total MAQLQ-M, SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) scores were avoidance coping, perceived recent financial difficulties and clinical asthma status. Additional independent associations were, for total MAQLQ-M, patient concerns about costs delaying them from seeking care (overall model r(2) = 0.69); for PCS, active coping (r(2) = 0.69) and for MCS, positive evaluations/satisfaction with illness (r(2) = 0.54).Conclusion: Psychological factors, particularly coping styles, need to be taken into account when considering HRQL scores as outcome measures in asthma. Interventions to improve the coping capabilities of individuals with moderate-to-severe asthma may be potentially important areas for improvement of asthma-related HRQL.

Background: The prevalence of undiagnosed asthma in the general population and the clinical and demographic characteristics of these patients compared with those with diagnosed asthma are unclear. Methods: The North West Adelaide Health Survey (NWAHS) is a population household interview survey of adults (age >18 years) in the north western suburbs of Adelaide, South Australia (regional population 0.6 million). Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to: “Have you ever had asthma?”; “Has it been confirmed by a doctor?”; ”Do you still have asthma?” determined current physician diagnosed asthma. A positive bronchodilator response on spirometric testing according to ATS criteria without a physician’s diagnosis determined undiagnosed asthma. Other measures included the SF-12 health survey questionnaire, the Selim index of severity of chronic lung disease, skin allergy tests, and demographic data. Results: Of the 3422 individuals interviewed, 2523 (74%) agreed to participate in the clinical assessment. Of these, 292 (11.6%) had asthma, 236 (9.3%) with a doctor’s diagnosis of asthma and 56 (2.3%) with undiagnosed asthma defined on spirometric criteria; thus, 19.2% of the total asthma group were undiagnosed. Those undiagnosed were more likely (p<0.05) to be >40 years old, on government benefits, with an income 65 years. Health service use over the previous year was similar for both asthma groups. Conclusion: Undiagnosed asthma is common among the Australian population, with a similar clinical spectrum to those with diagnosed asthma.

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.

Objectives: To assess trends in the prevalence of self-reported doctor-diagnosed asthma, associated asthma related morbidity, and the uptake of written asthma action plans in South Australia, 1990-2001.Design, setting and participants: Surveys by telephone interview of the South Australian population between 1990 and 2001, and interview of participants in their own homes by trained health interviewers.Main outcome measures: Asthma prevalence, percentage of patients with written action plans, and asthma associated morbidity.Results: The reported prevalence of doctor-diagnosed asthma has increased from 8% (95% CI, 6.4%-9.6%) in 1990 to 12.8% (95% CI, 11.4%-14.2%) in 2001. Morbidity, as measured by wakening at night (daily or weekly) and days lost from normal activities because of asthma, has remained constant over the decade. The percentage of patients with written asthma action plans increased to a peak of 42.3% (95% CI, 40.3%-44.3%) in 1995, but then declined to 22.2% (95% CI, 20.7%-23.7%) in 2001.Conclusions: The prevalence of asthma has increased while morbidity has remained constant, indicating that the burden of asthma has increased. The associated decline in the percentage of patients with asthma action plans in recent years is cause for concern.

Airway epithelial cells (AEC) contain both pro- and anti-apoptotic factors but little is known about mechanisms regulating apoptosis of these cells. In this study we have examined the localization of pro-caspase-3 and Zn(2+), a cellular regulator of pro-caspase-3, in primary sheep and human AEC. Zn(2+) was concentrated in both cytoplasmic vesicles and ciliary basal bodies, in the vicinity of both pro-caspase-3 and the antioxidant Cu/Zn superoxide dismutase (Cu/Zn SOD). Depletion of intracellular Zn(2+) in sheep AEC, using the membrane permeant Zn(2+) chelator TPEN, increased lipid peroxidation in the apical cell membranes (as assessed by immunofluorescence with anti-hydroxynonenal) as well as increasing activated pro-caspase-3 and apoptosis. There were smaller increases in caspase-2 and -6 but not other caspases. Activation of caspase-3 in TPEN-treated AEC was inhibited strongly by N-acetylcysteine and partially by vitamin C and vitamin E. These findings suggest that cytoplasmic pro-caspase-3 is positioned near the lumenal surface of AEC where it is under the influence of Zn(2+) and other anti-oxidants.

Zn may have an important protective role in the respiratory epithelium and Zn deficiency may enhance airway inflammation and epithelial damage. The effects of mild nutritional Zn deficiency on airway hyperresponsiveness (AHR) and airway inflammation in mice sensitized and challenged with ovalbumin (OVA) to induce an allergic response were investigated. Balb/c mice were given Zn normal (ZN, 50 mg/kg Zn) or Zn limited diets (ZL, 14 mg/kg Zn) before and during induction of allergic airway inflammation, with appropriate controls (saline-treated, SAL). ZL mice had greater levels of AHR than ZN mice, regardless of presence or absence of allergic inflammation. These mice also had increased eosinophilia and mucus cell hyperplasia compared with ZN mice. Second, ZN and ZL OVA-treated mice had significant decreases in airway epithelial Zinquin fluorescence, indicating a lowered availability of Zn compared with their SAL-treated counterparts. In contrast, the pro-apoptotic protein caspase-3, which was co-localized with Zn in the apical epithelium, was significantly increased in both ZN and ZL OVA-treated mice. Immunologically active caspase-3 and apoptosis were increased in OVA-treated mice, especially the ZL group. These findings provide the first data for adverse effects of Zn deficiency on the respiratory epithelium and support a role for altered Zn homeostasis and caspase upregulation in asthma.

Objectives: To evaluate the effectiveness of coordinated care for chronic respiratory disease.Design and setting: Community-based geographical control study, in western (intervention) and northern (comparison) metropolitan Adelaide (SA).Participants: 377 adults (223 intervention; 154 comparison) with chronic obstructive pulmonary disease, asthma or other chronic respiratory condition, July 1997 to December 1999.Intervention: Coordinated care (includes care coordinator, care guidelines, service coordinator and care mentor).Main outcome measures: Hospital admissions (any, unplanned and respiratory), functionality (activities of daily living) and quality of life (SF-36 and Dartmouth COOP).Results: At entry to the study, intervention and comparison subjects were dissimilar. The intervention group was 10 years, older (P < 0.001), less likely to smoke (P = 0.014), had higher rates of hospitalisation in the previous 12 months (P < 0.001) and had worse self-reported quality of life (SF-36 physical component summary score [P < 0.001] and four of nine COOP domains [P = 0.002-0.013]). After adjustment for relevant baseline characteristics, coordinated care was not associated with any difference in hospitalisation, but was associated with some improvements in quality of life (SF-36 mental component summary score [P = 0.023] and three of nine COOP domains [P = 0.008-0.031]) compared with the comparison group.Conclusions: Coordinated care given to patients with chronic respiratory disease did not affect hospitalisation, but it was associated with an improvement in some quality-of-life measures.

Objectives. To determine the natural history of infant spilling (regurgitation/vomiting) during the first 2 years of life and to determine the relationship between infant spilling and gastroesophageal reflux (GER) symptoms at 9 years of age.Methods. A prospective birth cohort was followed with daily symptom diaries during the first 2 years of life and reviewed at 9 years of age (range: 8-11 years). The prevalence of infant spilling during the first 2 years of life, the prevalence of GER symptoms between 8 and 11 years of age (mean age: 9.7 years), relative risk of infant spilling predisposing to GER symptoms at 9 years of age, and prevalence of maternal GER symptoms and relationship with infant spilling and GER at 9 years of age were measured.Results. A total of 693 children who represented 83% of an original sample of 836 children and were followed for 2 years from birth with daily symptom diaries were contacted at 9 (8-11) years of age. Spilling of most feeds each day was common in infancy and reached a peak prevalence of 41% between 3 and 4 months of age and thereafter declined to <5% between 13 and 14 months of age. Infants with spilling on 90 days or more during the first 2 years of life (classified as frequent spilling) were more likely to have GER symptoms at 9 years of age. Children with frequent infant spilling, compared with those with no spilling, had a relative risk of 2.3 (95% confidence interval [CI]: 1.3-4.0) of 1 or more GER symptoms at 9 years of age, 4.6 (95% CI: 1.5-13.8) for heartburn, 2.7 (95% CI: 1.4-5.5) for vomiting, and 4.7 (95% CI: 1.6-14.0) for acid regurgitation. Gender, breastfeeding, and environmental tobacco smoke exposure were not significant factors related to infant spilling. Prepregnancy smoking and smoking in the same room as the child at the 9-month and 18-month follow-ups had a significant effect on GER symptoms at 9 years of age. Infant spilling and GER at 9 years of age were significantly related to maternal GER symptoms but not to paternal GER symptoms.Conclusions. Spilling in infancy is very common, but the majority of children settle by 13 to 14 months of age. However, those with frequent spilling (> 90 days) are more likely to have GER symptoms at 9 years of age. In addition, a maternal history of GER was significantly related both to infant spilling and to GER at 9 years, suggesting that a genetic component may be involved. Physicians should consider studying children with a history of frequent infant spilling to determine whether this group is at increased risk for GER disease.

OBJECTIVES:To identify factors associated with asthma patients' perceptions of the propensity of pulmonologists to involve them in treatment decision-making, and its association with asthma outcomes. DESIGN:Cross-sectional observational study performed from June 1995 to December 1997. SETTING:Pulmonary unit of a university teaching hospital. PATIENTS:Adult patients with asthma (n = 128). MEASUREMENTS AND RESULTS:By patient self-report, mean physician's participatory decision-making (PDM) style score was 72 (maximum 100, 95% CI 65, 79). PDM scores were significantly correlated (P < .0001) with the duration of clinic visits (r = .63), patient satisfaction (r = .53), duration of tenure of doctor-patient relationship (r = .37), and formal education (r = .22, P = .023). Significantly higher PDM style scores were reported when visits lasted longer than 20 minutes and when a patient had a >6-month relationship with a particular doctor. PDM scores were also significantly correlated with possession of a written asthma action plan (r = .54, P < .0001), days affected by asthma (r = .36, P = .0001), asthma symptoms (r = .23, P = .017), and preferences for autonomy in asthma management decisions (r = .28, P = .0035). Those with PDM scores <50 reported significantly lower quality of life for all domains of a disease-specific instrument and the Short-Form 36 health survey version 1.0. In multiple regression analysis, PDM style was associated with the length of the office visit and the duration of tenure of the physician-patient relationship (R2 = 0.47, P = .0009). The adjusted odds ratio, per standard deviation decrease in PDM scores, for an asthma hospitalization was 2.0 (95% CI 1.2, 3.2) and for rehospitalization was 2.5 (95% CI 1.2, 4.2). CONCLUSIONS:Patients' report of their physician's PDM style is significantly associated with health-related quality of life, work disability, and recent need for acute health services. Organizational factors, specifically longer visits and more time seeing a particular physician, are independently associated with more participatory visits. This has significant policy implications for asthma management.

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.

OBJECTIVES:To describe patterns of hospital readmission for asthma in South Australia from 1989 to 1996, in relation to implementation of the National Asthma Campaign.DESIGN AND SETTING:A comparison of hospital admissions in South Australia of patients aged between one year and 49 years for three conditions: asthma (or respiratory failure with asthma as an underlying condition) and two control conditions--diabetes and epilepsy. Individuals were identified by Medicare number and date of birth.OUTCOME MEASURES:Hospital readmission within 28 days and within one year.RESULTS:Overall, by 1996, there was a statistically significant decline in the risk of readmission for asthma within 28 days of 18% and within one year of 17% compared with 1989 readmission rates. There were no reductions in the risk of readmission for diabetes or epilepsy, suggesting that the decline in risk of readmission for asthma was greater than the underlying effects of general changes in hospital casemix.CONCLUSIONS:The decline in risk of readmission may reflect changes in asthma severity or improved management practices. However, hospital readmission rates still remain high, and to further reduce readmissions for asthma there is a need to identify factors related to presentation for asthma at accident and emergency departments.

To produce a scale useful for individual clinical decision making, the Marks Asthma Quality of Life Questionnaire (AQLQ-M) was modified to a 22-item scale using a 7-point Likert response scale, and the validity of the new instrument was assessed. Adult asthma subjects with moderate to severe disease, recruited from two hospitals in Adelaide, Australia, were surveyed at baseline (n = 293), and at 3-month follow-up (n = 234). Cronbach's a for the Total scale of the modified AQLQ-M (MAQLQ-M) was 0.97 and all subscale values exceeded 0.90. Test-retest reliability values for all scales were between 0.88 and 0.93. All correlations between disease reference measures were statistically significant to at least the p < 0.01 level. Stronger associations were seen with symptom and self-rating scales than for lung function, medication usage, and health service utilization measures of outcome. The MAQLQ-M showed good discriminative ability for all asthma symptom categories and for different FEV, values. Moderate, statistically significant associations were seen between changes in MAQLQ-M scores and clinical measures. Higher baseline MAQLQ-M scores were associated with lower risks over 12 months for hospital admissions (odds ratio, OR = 0.58) and repeated emergency department visits (OR = 0.47). The MAQLQ-M is a highly valid measure of asthma-related quality of life.

The respiratory epithelium is vulnerable to noxious substances, resulting in the shedding of cells and decreased protection. Zinc (Zn), an antioxidant and cytoprotectant, can suppress apoptosis in a variety of cells. Here we used the novel Zn-specific fluorophore Zinquin to visualize and quantify labile intracellular Zn in respiratory epithelial cells. Zinquin fluorescence in isolated ciliated tracheobronchial epithelial cells and intact epithelium from sheep and pigs revealed an intense fluorescence in the apical and mitochondria-rich cytoplasm below the cilia. Zinquin fluorescence was quenched by the Zn chelator N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and increased by the Zn ionophore pyrithione. We also assessed whether changes in intracellular labile Zn would influence susceptibility of these cells to apoptosis by hydrogen peroxide. Our results confirm that Zn deficiency enhanced hydrogen peroxide-induced caspase activation from 1.24 +/- 0.12 to 2.58 +/- 0.53 units. microg protein(-1). h(-1) (P </= 0.05); Zn supplementation suppressed these effects. These findings are consistent with the hypothesis that Zn protects upper respiratory epithelial cells and may have implications for human asthma where there is hypozincemia and epithelial damage.

Household gas appliances produce nitrogen dioxide (NO2), which may be associated with an increase in symptoms in asthmatics. The relationship between indoor NO2 exposure, and respiratory symptoms in people with asthma was evaluated. Self-reported asthmatics (n=125) wore lapel badges that measured NO2 daily over 6 weeks at home. Outdoor pollutants, spores and meteorological parameters were measured daily, in addition to smoking status and demographic factors. Seven asthma symptoms were recorded in diaries, for analysis by same day and also with 1 day lag exposures, using a generalized estimating equation. Significant interactions were demonstrated between NO2 at age < or =14 yrs, with respect to the symptoms of chest tightness on the same day (odds ratio (OR): 1.29, 95% confidence interval (CI): 1.16-1.43) and with a 1 day lag (OR: 1.29, 95% CI: 1.14-1.46), breathlessness on exertion with a 1 day lag (OR: 1.13, 95% CI: 1.00-1.28), daytime asthma attacks on the same day (OR: 1.13, 95% CI: 1.02-1.26) night asthma attacks on the same day (OR: 1.16, 95% CI:1.03-1.30) and with a 1 day lag (OR: 1.15, 95% CI; 1.03-1.29) after adjustment for potential confounders. A significant interaction between NO2 and age 35-49 yrs was demonstrated for coughs with a 1 day lag (OR: 1.15, 95% CI: 1.01-1.31). Daily personal exposures to NO2 are associated with asthmatic symptoms in children.