The health behaviour and clinical characteristics of ambulance users with acute asthma.

OBJECTIVE: This study sought to determine if ambulance service users differ in their health behaviours to "walk-in" patients attending an emergency department (ED) with acute asthma. METHOD: Retrospective cross-sectional study of people with acute asthma stratified by ambulance use attending two ED. The health-promoting lifestyle profile and health risk appraisal tools assessed health and risk-taking behaviours, and the clinical variables assessed include: forced expiratory volume in 1 s, admission rates, severity, asthma medications, anxiety and depression. RESULTS: Of the 142 patients, 26% used the ambulance service as transport to the ED. Ambulance users were significantly older than walk-in patients (40 vs 32 years, p < or = 0.05) and were less likely to return to follow-up appointments (odds ratio (OR) 2.93, 95% CI 1.16 to 7.37). Walk-in patients were more likely to report higher levels of education (OR 4.36, 95% CI 1.11 to 17.09). There was no difference between the groups for health-promoting behaviours. In reducing risks to their health and after adjusting for age and gender, there was a trend towards ambulance users undertaking preventive health measures more often than walk-in patients. CONCLUSIONS: Ambulance users with acute asthma are more likely to be older, married and less educated. There is no evidence that this group is less responsible in managing their health; however, fewer ambulance users attended their follow-up appointment and the implication for ongoing care requires further investigation.

The effects of salbutamol, beclomethasone, and dexamethasone on fibronectin expression by cultured airway smooth muscle cells.

Possible mechanisms of adverse drug effects in asthma include worsening of cellular hyperplasia and stimulation of extracellular matrix deposition. In this study, salbutamol, dexamethasone and beclomethasone were investigated to ascertain their ability to induce mitogenesis and stimulate fibronectin expression in cultured canine airway smooth muscle cells. In cells maintained in serum-free media for 72 h, salbutamol (1 nM-10 microM) caused mitogenesis. The control cells had 2.57 +/- 0.34 x 10(5) cells per ml (mean +/- SEM, N = 13), while salbutamol (1 microM) caused a maximal increase in cell number to 3.57 +/- 0.23 x 10(5) cells/ml (P < 0.01). In cells stimulated to replicate by addition of either fetal bovine serum or canine serum, no additional mitogenic effect of salbutamol was seen. Salbutamol did not have a detectable quantitative effect on fibronectin matrix expression. The glucocorticoids, beclomethasone and dexamethasone, significantly altered fibronectin expression by cultured airway smooth muscle cells. Beclomethasone increased fibronectin expression, while dexamethasone decreased expression.

Are antipseudomonal antibiotics really beneficial in acute respiratory exacerbations of cystic fibrosis?

BACKGROUND: Although anti-pseudomonal antibiotics are routinely used in the treatment of acute respiratory exacerbations of adult cystic fibrosis (CF), the specific efficacy of such treatment remains uncertain, the mechanism of action of these agents is not fully understood, and the role of sputum susceptibility testing in clinical decision making is controversial. AIMS: We investigated the relationship between susceptibility testing and clinical outcome in adult CF patients colonised with Pseudomonas aeruginosa. METHODS: Sputum samples were collected before, during and after respiratory exacerbations from 31 admissions (17 patients). Sputum colony counts and MIC of P. aeruginosa were performed. RESULTS: Sputum colony counts did not change significantly during or after intravenous (IV) antibiotic therapy. Clinical outcome parameters (lung function, 12-minute walking distance, sputum weight and quality of life) were compared with susceptibility of P. aeruginosa colonies isolated at admission to the antibiotics used, and no correlation was evident. There was no evidence for the development of cross-resistance and there was no change in the proportion of mucoid colonies with therapy. CONCLUSIONS: While this study has a small patient sample size, it highlights the inconsistency of the role of antipseudomonal drugs also shown in other similar studies. The presence of P. aeruginosa in sputum of acutely ill CF patients prompts us to prescribe i.v. antipseudomonal drugs. If this approach was valid, we would expect to find a reduction in sputum colony counts and improvement in clinical parameters with the use of antibiotics to which the organisms were sensitive. The fact that such a relationship cannot be consistently demonstrated in this and other studies suggests that the use of antipseudomonal therapy in these patients requires more critical bacteriological and clinical evaluation.

Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis.

Various treatment regimens and difficulties with research design are encountered with cystic fibrosis (CF) because no standard diagnostic criteria exist for defining acute respiratory exacerbations. This study evaluated the role of serial monitoring of concentrations of selected cytokines and inflammatory mediators in serum and sputum as predictors of respiratory exacerbation, as useful outcome measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured in serum and sputum collected from CF patients during respiratory exacerbations and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerbations and fell after institution of antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively). Mean (+/- standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not change significantly with clinical deterioration of the patient (P > 0.23). IL-8 and TNF-alpha were generally undetectable in serum, and therefore these measures were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or laboratory parameter that was close to being a determinant of respiratory exacerbation (P = 0.055). This study provides evidence of intense immunological activity occurring continually within the lungs of adult CF patients. Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identifying acute respiratory exacerbations.

Buteyko breathing techniques in asthma: a blinded randomised controlled trial.

OBJECTIVE: To evaluate the effect of Buteyko breathing techniques (BBT) in the management of asthma. DESIGN: Prospective, blinded, randomised study comparing the effect of BBT with control classes in 39 subjects with asthma. The study was conducted from January 1995 to April 1995. PARTICIPANTS AND SETTING: Subjects recruited from the community, aged 12 to 70 years, with asthma and substantial medication use. MAIN OUTCOME MEASURES: Medication use; morning peak expiratory flow (PEF); forced expiratory volume in one second (FEV1); end-tidal (ET) CO2; resting minute volume (MV); and quality of life (QOL) score, measured at three months. RESULTS: No change in daily PEF or FEV1 was noted in either group. At three months, the BBT group had a median reduction in daily beta 2-agonist dose of 904 micrograms (range, 29 micrograms to 3129 micrograms), whereas the control group had a median reduction of 57 micrograms (range, -2343 micrograms to 1143 micrograms) (P = 0.002). Daily inhaled steroid dose fell 49% (range, -100% to 150%) for the BBT group and 0 (range, -82% to +100%) for the control group (P = 0.06). A trend towards greater improvement in QOL score was noted for BBT subjects (P = 0.09). Initial MV was high and similar in both groups; by three months, MV was lower in the BBT group than in the control group (P = 0.004). ET CO2 was low in both groups and did not change with treatment. CONCLUSION: Those practising BBT reduced hyperventilation and their use of beta 2-agonists. A trend toward reduced inhaled steroid use and better quality of life was observed in these patients without objective changes in measures of airway calibre.

Home intravenous therapy in cystic fibrosis: a prospective randomized trial examining clinical, quality of life and cost aspects.

In this study, we set out to determine if home intravenous (i.v.) antibiotic therapy in adult patients with cystic fibrosis (CF) is a feasible, effective and less costly alternative to hospitalization, and to assess the impact of home therapy on quality of life. The study was a prospective, randomized, two-factor mixed design involving adults presenting with respiratory exacerbations of CF. Patients were randomized such that they were discharged home after 2-4 days, or remained in hospital. Seventeen patients had 31 admissions (13 home and 18 hospital). Following 10 days of therapy, there were no significant differences between home or hospital arms with respect to body weight, 12 minute walking distance, sputum weight, pulse oximetry, or improvement in lung function (forced expiratory volume in one second (FEV1), or forced vital capacity (FVC)). Patients who remained in hospital were less fatigued and noted a greater degree of mastery. Patients discharged early noted less disruption to their family life, personal life and sleeping pattern. The total cost for the home therapy arm was approximately half that of the hospital therapy arm. Home intravenous antibiotic therapy in patients with cystic fibrosis was a feasible, cost-effective alternative to receiving therapy in hospital. Although there was no clinical compromise associated with home therapy, there were advantages and disadvantages in terms of quality of life.

Homologous serum increases fibronectin expression and cell adhesion in airway smooth muscle cells.

This study describes altered patterns of growth and upregulation of fibronectin expression of cultured canine airway smooth muscle cells grown in homologous serum, which provides a model of the vascular leakage occurring in asthma, compared to fetal bovine serum (FBS). Cells were incubated in increasing concentrations of serum (2.5-40%) for 72 hours. Both homologous serum and FBS caused cellular proliferation which reached a maximum increase at 2.5-5% serum concentration. Differences in the cellular responses to the two types of sera were noted at higher concentrations of sera. At a concentration of 40% FBS, airway smooth muscle cells increased in number by 307 +/- 16% (n = 5) compared to serum-free control cells, whereas in canine serum the increase in growth was significantly smaller, 239 +/- 25% (n = 7) (P < 0.05). Airway fibrocytes similarity treated increased in number by 256 +/- 43% (n = 3) in 40% FBS, but exhibited a reduction in cell number to 80 +/- 10% (n = 3) of controls in 40% homologous serum (P < 0.05). Smooth muscle cells demonstrated a dose-dependent increase in fibronectin expression when grown in homologous serum but not in FBS, suggesting phenotypic change occurred in these cells when exposed to homologous serum. These data suggest that the leakage of plasma in the asthmatic airway may trigger phenotypic change in both airway smooth muscle cells and airway fibrocytes leading to cellular proliferation and expression of extracellular matrix molecules. These in vitro changes are consistent with the histological findings in clinical asthma.

Measuring the systemic effects of inhaled beclomethasone: timed morning urine collections compared with 24 hour specimens.

BACKGROUND: Inhaled glucocorticoid therapy has systemic effects including hypothalamic-pituitary-adrenal (HPA) suppression. The optimal test for detecting these effects has not been defined. METHODS: Timed urine collections and 09.00 hour plasma cortisol levels were obtained from 12 normal volunteers receiving inhaled placebo, beclomethasone (BDP) 800 or 2000 micrograms/day. The 24 hour urine samples were collected as follows: first hour after waking (hour 1), the next two hours after waking (hours 2 and 3), remainder of day, and overnight, with results expressed as urine cortisol/creatinine (UCC) ratios and as hourly cortisol output in the timed collections. Twenty four hour urinary cortisol excretion was also calculated. Medication was blinded and given in random order with a washout period of at least 11 days between each treatment arm. RESULTS: None of the UCC ratios changed with BDP 800 micrograms/day. UCC ratios at hour 1, hour 2 and 3, and overnight, and 24 hour urinary free cortisol excretion were reduced after BDP 2000 micrograms/day, whilst remainder of day UCC ratio and the plasma cortisol level did not change significantly. Cortisol output showed similar changes. In a follow up study BDP 1400 micrograms/day also reduced UCC ratios for the first two hours after waking. CONCLUSIONS: UCC ratios are as sensitive as the more cumbersome 24 hour urinary free cortisol excretion, and more sensitive than single morning plasma cortisol measurements, in detecting the effects of inhaled beclomethasone on the HPA axis.

Airway smooth muscle proliferation in asthma: the potential of vascular leakage to contribute to pathogenesis.

Proliferation of the non-vascular smooth muscle in the walls of the bronchi and bronchioles is a prominent histopathological feature of asthma and is thought to contribute to airway hyperreactivity and narrowing. Increased vascular permeability with plasma leakage is also a feature of asthma pathology and causes submucosal oedema. We hypothesize that, in asthmatics, the accumulation of enriched plasma in the environment surrounding airway smooth muscle promotes respiratory smooth muscle mitogenesis and hyperplasia. This situation represents the in vivo correlate of the increase in airway smooth muscle cell growth seen in vitro with increasing concentrations of serum in the culture medium. Thus, we hypothesize that vascular leakage in the airways in asthma is a primary pathogenic event leading to airway smooth muscle hyperplasia and hypertrophy, and consequently airway narrowing, promoting the characteristic bronchial hyperreactivity associated with narrowing of the airway lumen.

Heparin inhibits the immediate response to antigen in the skin and lungs of allergic subjects.

Although heparin is used as an anticoagulant, its biologic function remains unclear. Substantial evidence exists that suggests it may modulate many aspects of immune function and inflammation. We demonstrated, in a double-blind, placebo-controlled, crossover study involving 10 allergic subjects, that a small dose of heparin (25 U/kg) administered intravenously 10 min before challenge reduced the acute cutaneous reaction to 10 allergens and histamine from a group-average sum of mean (+/- SD) wheal diameters at a baseline of 29.9 +/- 10 mm and after normal saline placebo (29.5 +/- 10.7 mm) to after heparin (14.4 +/- 10.4 mm) (p < 0.02, Wilcoxon's signed rank test). In 15 subjects with asthma and dust mite allergy, nebulized heparin 20,000 units administered in a double-blind, placebo-controlled, crossover fashion 10 min before challenge inhibited the bronchospasm induced by inhaled dust mite extract. Log2 of the provocative dose of mite extract causing a 20% fall in FEV1 at baseline was 4.1 +/- 1.5 protein nitrogen units (PNU); after normal saline it was 4.5 +/- 2.0 PNU, and after heparin it was 5.1 +/- 2.5 PNU (p = 0.04). These data suggest heparin may have an inhibitory role in acute mast-cell-mediated allergic inflammation.

Corticosteroids in acute severe asthma: effectiveness of low doses.

BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known. METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days. RESULTS: The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose. CONCLUSIONS: Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.

Nebulized fenoterol and i.v. aminophylline in acute severe asthma.

We investigated the bronchodilator effect of intravenous aminophylline given after a cumulative dose of nebulized fenoterol of 2.4 mg in 18 patients with acute severe asthma. The mean forced expiratory volume in 1 s (FEV1) +/- SD before treatment was 0.72 +/- 0.22 l. The mean improvement in FEV1 after fenoterol was 0.64 +/- 0.39 l (85% of total improvement) and after aminophylline 0.11 +/- 0.13 l (15% of total improvement). The improvement after aminophylline was statistically significant (p less than 0.01), though quantitatively small. Thirteen patients improved after aminophylline by less than 0.15 l, and in only five was the improvement 0.2-0.4 l. There was no significant change in heart rate and subjective tremor score with treatment, although observed tremor (0 = absent, 4 = maximum) increased from 0.4 +/- 0.6 to 1.3 +/- 1.0 after all treatment. For the majority of patients presenting with acute severe asthma, it is likely that high doses of nebulized beta-2 agonist alone will produce near maximal bronchodilation in the short term.

House dust control and asthma: a placebo-control trial of cleaning air filtration.

Using a placebo-control single-blind crossover trial, we investigated the effects of dust control measures alone and combined with electrostatic and high efficiency particulate air filters in the bedrooms of patients with asthma. Of 12 young asthmatics allergic to house dust and dust mite who entered the trial, nine completed all four 2-week intervals. No statistically significant improvement in symptom scores or peak expiratory flow above that recorded during the placebo interval occurred during any treatment phase. We conclude that house dust suppression adds little to the management of otherwise well controlled young asthmatic patients.