Richard E. Ruffin

Factors associated with hospital admissions and repeat emergency department visits for adults with asthma

BACKGROUND A small proportion of patients with asthma account for a disproportionate number of acute health service events. To identify whether factors other than severity and low socioeconomic status were associated with this disproportionate use, a prospective study was undertaken to examine management and psychosocial factors associated with increased risk for admission to hospital with asthma and repeat visits to the emergency department over a 12 month period. METHODS A total of 293 patients with moderate or severe asthma managed at least in part at two teaching hospitals completed surveys of clinical status, acute events, sociodemographic, and psychological variables. RESULTS Twenty three percent had a single admission to hospital and 16% had two or more hospital admissions. Twenty six percent had one emergency department visit and 32% had two or more visits to the emergency department. In a multiple logistic regression model, adjusted for age, sex, education and income, odds ratios (95% CI) for baseline factors associated with hospital admissions over the next 12 months were: moderate severity compared with severe asthma 0.6 (0.2 to 0.9); no hospital admissions in the past 12 months 0.1 (0.01 to 0.2); not possessing a written asthma action plan 4.0 (1.5 to 10.7); less use of an avoidance coping style 0.4 (0.3 to 0.7); lower preferences for autonomy in asthma management decisions 1.4 (0.96 to 2.0). Adjusted odds ratios (95% CI) for repeat emergency department visits were: moderate asthma severity 0.3 (0.1 to 0.8); current regular use of oral corticosteroids 10.0 (3.1 to 32.4); a hospital admission in the past 12 months 2.9 (1.8 to 4.8); not possessing a written asthma action plan 2.2 (1.1 to 5.6); less dislike of asthma medications 0.7 (0.5 to 0.9). CONCLUSIONS In addition to factors relating to severity, not possessing a written asthma action plan, avoidance coping, and attitudes to self-management were related to acute use of health services in this at risk group. Interventions need to address or take these factors into account to reduce asthma morbidity.

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.

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.

RESTRICTIONS ON SMOKING AT HOME AND URINARY COTININE LEVELS AMONG CHILDREN WITH ASTHMA

OBJECTIVES The purpose of this study was to determine the extent to which various levels of restrictions on smoking in the home may be associated with childrens exposure to environmental tobacco smoke (ETS). METHODS The methodology consisted of a cross-sectional survey involving 249 children with asthma aged 1 to 11 attending hospital outpatient clinics, with at least one parent who smoked, linked to the childs urinary cotinine to creatinine ratios (CCR). RESULTS After adjustment for childs age, mothers smoking status, and total parental daily cigarette consumption, a total ban was associated with significantly lower urinary CCR levels (7.6 nmol/mmol) than bans with exceptions or limited smoking in the home. Where exceptions to bans were made (14.9 nmol/mmol), childrens urinary CCR levels were no different from homes in which smoking was allowed in rooms the child rarely frequented (14.1 nmol/mmol). These two intermediate levels of restriction were in turn associated with significantly lower CCR levels than unrestricted smoking in the home (26.0 nmol/mmol). CONCLUSIONS Making exceptions to bans on smoking at home measurably undermines the protective effect of a ban. However, making some exceptions to a ban and limiting smoking to rooms where the child rarely goes may result in reduced exposure to ETS, compared with unrestricted smoking.

Psychological factors and asthma quality of life: a population based study

Background: Reports of psychological conditions in asthmatic subjects have been limited to certain population groups or convenience samples. A study was undertaken of the prevalence of psychological distress in asthma in the general population and its associations with quality of life. Methods: The WANTS Health and Well-being Survey is a population household interview survey of adults (age ⩾18) in Western Australia, the Northern Territory, and South Australia. Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to two questions: “Have you ever been told by a doctor that you have asthma?” and “Do you still have asthma?” determined current doctor-diagnosed asthma. Other items included the SF-12, the Kessler-10 index of psychological distress, questions on feelings of lack of control in different areas of life, and on mental health conditions. Results: From the available sample of 10 080, 7619 interviews were completed (participation rate 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). Psychological distress was more frequent in those with asthma (17.9% v 12.2%, p<0.01) and a higher proportion with asthma were at higher risk for anxiety or depression (40.5% v 31.2%, p<0.01). Mental health conditions were also more common (16.2% v 10.8%, p<0.01), as was the frequency of those who sometimes or always felt a lack of control over their health (33.5% v 24.3%, p<0.01). People with both asthma and psychological distress had significantly lower scores on the SF-12 physical component summary (PCS) than those with either asthma or distress alone. Among those with psychological distress, mental component summary (MCS) scores did not differ between asthmatic and non-asthmatic respondents. In a multiple regression model the frequency of a feeling of lack of control over health—together with age, family’s financial situation, education level, and number of days partially unable to work or perform usual duties—was significantly associated with scores on the PCS (r = 0.73, adjusted r2 = 0.54). Conclusion: These results, from a representative population sample, show that psychological distress and decreased feelings of control are common in asthma and are significantly associated with physical health status.

New insights into the role of zinc in the respiratory epithelium

Over the past 30 years, many researchers have demonstrated the critical role of zinc (Zn), a group IIb metal, in diverse physiological processes, such as growth and development, maintenance and priming of the immune system, and tissue repair. This review will discuss aspects of Zn physiology and its possible beneficial role in the respiratory epithelium. Here we have detailed the mechanisms by which Zn diversely acts as: (i) an anti‐oxidant; (ii) an organelle stabilizer; (iii) an anti‐apopototic agent; (iv) an important cofactor for DNA synthesis; (v) a vital component for wound healing; and (vi) an anti‐inflammatory agent. This paper will also review studies from the authors’ laboratory concerning the first attempts to map Zn in the respiratory epithelium and to elucidate its role in regulating caspase‐3 activated apoptosis. We propose that Zn, being a major dietary anti‐oxidant has a protective role for the airway epithelium against oxyradicals and other noxious agents. Zn may therefore have important implications for asthma and other inflammatory diseases where the physical barrier is vulnerable and compromised.

Cohort Profile: The North West Adelaide Health Study (NWAHS)

Published by Oxford University Press on behalf of the International Epidemiological Association

Health effects of daily indoor nitrogen dioxide exposure in people with asthma

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.

Labile zinc and zinc transporter ZnT4 in mast cell granules: Role in regulation of caspase activation and NF-KB translocation

The granules of mast cells and other inflammatory cells are known to be rich in zinc (Zn), a potent caspase inhibitor. The functions of granular Zn, its mechanism of uptake, and its relationship to caspase activation in apoptosis are unclear. The granules of a variety of mast cell types fluoresced intensely with the Zn-specific fluorophore Zinquin, and fluorescence was quenched by functional depletion of Zn using a membrane-permeable Zn chelator N, N, N′, N′-tetrakis (2-pyridyl-methyl)ethylenediamine (TPEN). Zn levels were also depleted by various mast cell activators, including IgE/anti-IgE, and Zn was rapidly replenished during subsequent culture, suggesting an active uptake mechanism. In support of the latter, mast cells contained high levels of the vesicular Zn transporter ZnT4, especially in the more apical granules. Immunofluorescence and immunogold labeling studies revealed significant pools of procaspase-3 and -4 in mast cell granules and their release during degranulation. Functional depletion of Zn by chelation with TPEN, but not by degranulation, resulted in greatly increased susceptibility of mast cells to toxin-induced caspase activation, as detected using a fluorogenic substrate assay. Release of caspases during degranulation was accompanied by a decreased susceptibility to toxins. Zn depletion by chelation, but not by degranulation, also resulted in nuclear translocation of the antiapoptotic, proinflammatory transcription factor NF-κB. These findings implicate a role for ZnT4 in mast cell Zn homeostasis and suggest that granule pools of Zn may be distinct from those regulating activation of procaspase-3 and NF-κB.

Involvement of redox events in caspase activation in zinc-depleted airway epithelial cells.

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.