Formoterol Turbuhaler as reliever medication in patients with acute asthma.

The aim of this study was to compare the efficacy and safety of formoterol versus salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 microg in the number of patients studied.

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.

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.

Patients prefer sedation for fibreoptic bronchoscopy.

This study was carried out in order to determine if intravenous (i.v.) sedation with diazepam, at the time of procedure, made fibreoptic bronchoscopy more tolerable and if these perceptions persisted on later questioning. Methodology consisted of a sequential, parallel group design comparing sedation with no sedation for bronchoscopy in a tertiary referral hospital. Patient comfort and sedation desired for hypothetical repeat bronchoscopy were assessed both immediately and after at least 1 month. Patients who received sedation rated bronchoscopy as more comfortable (P = 0.01). Those who received sedation were also more likely to want no change in sedation if the bronchoscopy were repeated (P < 0.01). These differences were more evident at later questioning. Sedation was not associated with an increased complication rate but was associated with a prolonged recovery room stay (no sedation, 19.2 min (SEM 3.8) compared with sedation, 76.1 min (5.4), P < 0.001). In contrast to previous studies, our patients found bronchoscopy more comfortable with i.v. diazepam sedation. This was supported by patients who received sedation being less likely to want any change in future sedation if a repeat bronchoscopy were required. The benefit seen with sedation was more marked at later questioning supporting a previously postulated amnesic effect. However, sedation was associated with a prolonged room stay and potentially greater attendant cost.

Bone mineral density and bone turnover in asthmatics treated with long-term inhaled or oral glucocorticoids.

Inhaled glucocorticoids are pivotal in maintenance therapy of chronic bronchial asthma; however, conflict exists over their effects on bone and mineral metabolism. We measured bone mineral density (BMD), bone turnover markers, and adrenal steroid hormones in 53 patients (34 female, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of > or = 1500 microg/day for at least 12 months to determine pathogenetic mechanisms of bone loss. To account for the effect of prior oral glucocorticoid exposure we divided patients into two groups: one with (OG) and the other without (IG) a past history of maintenance (> 1 month) oral glucocorticoid therapy. Lumbar spine (LS) and proximal femur BMDs were approximately 1 SD lower in men and women taking OG or high-dose IG for chronic bronchial asthma, potentially equivalent to a doubling of the risk of fracture at these sites. Prior exposure to OG in women was also associated with lower LS and proximal femur BMDs, while men were more sensitive to the adverse effects of IG on LS and Ward's triangle BMDs. Bone formation markers were decreased; however, bone resorption marker concentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both total duration of OG and biochemical bone turnover marker concentrations were negatively related to proximal femur and rib BMDs and total body bone mineral content, but not to LS BMD. These were stronger for bone resorption markers. Uncoupling of ongoing normal bone resorption from suppressed bone formation may therefore contribute to glucocorticoid-associated bone loss in asthma. Adrenal androgen suppression may also increase the susceptibility of postmenopausal women in particular to bone loss with OG. Although the effects of high-dose IG on BMD are associated with lower LS BMD in men, this observation should now be investigated further in prospective studies.

Chronic lung diseases and the perception of breathlessness: a clinical perspective.

Breathlessness is an extremely common symptom. Its genesis is incompletely understood but is known to be largely determined by many of the mechanical factors associated with the act of breathing. As with all subjective sensations various other factors including volition, behavioural style and other cortical and subcortical factors play a part in its genesis. The relief of breathlessness is primarily directed at the underlying disorder. In those conditions and situations where specific therapy has little to offer or little impact it is reasonable to consider ways of reducing the perception of breathlessness by pharmacological means. However, to date there is no convincing evidence that use of drugs in the pursuit of the relief of breathlessness has any specific effect in modifying the perception of this often distressing symptom. Any reduction in breathlessness achieved in this way can be adequately explained in terms of a reduction in ventilation and other indices of respiratory mechanics.

Accuracy of asthma death statistics in Australia.

Asthma mortality statistics issued by the Australian Bureau of Statistics (ABS) were compared with clinical data from a survey of asthma mortality. Deaths in Victoria from May 1986 to April 1987 containing 'asthma' in Parts 1 or 2 of the death certificate (N = 405) were reviewed. For each subject, the cause of death attributed by the Victorian Asthma Mortality Survey was compared with the ABS cause of death, by age and sex of the subject. Information on 393 of the 405 deaths investigated by the Victorian Asthma Mortality Survey was analysed. The ABS estimate of the total number of asthma deaths in Victoria was 47 per cent higher than the estimate of the Victorian Asthma Mortality Survey. In subjects under 50 years of age the two estimates were within 10 per cent. The difference between the estimates increased with age at death for persons over 50 years old and was equivalent for males and females. If the assessment by the Victorian Asthma Mortality Survey of the number of deaths due to asthma is accepted as accurate, then the ABS estimate of asthma deaths was reliable for those under 50 years of age. In those who died at an older age, the ABS significantly overestimated the number of deaths due to asthma in Victoria.

Pediatric asthma deaths in Victoria: the mild are at risk.

Previous reviews of pediatric asthma mortality have mostly been from hospital-based clinic populations and suggest that only those with severe asthma are most at risk. This report summarizes an investigation, by interviewer-administered questionnaire, into the circumstances surrounding the death in all patients aged 20 years or less who died from asthma in the State of Victoria over a 3 year period from May 1, 1986. During this period, 51 deaths due to asthma were reported. Thirty-three percent of these were judged to have a history of trivial or mild asthma, and 32% had no previous hospital admission for asthma. However, 36% were judged to have had severe asthma, 43% were taking regular inhaled beclomethasone or sodium cromoglycate, and 10% were taking regular oral steroids. Twenty-two percent had a previous admission to an ICU. Death occurred outside hospital in 40 (78%) subjects. In the final attack 63% had sudden onset and collapse within minutes, 12% were found dead, and 25% had acute progression of an established attack. The investigators assessed 39% of the deaths to have had potentially preventable elements. The preventable factors included: inadequate assessment or therapy of prior asthma (68%), poor compliance with therapy (53%), and delay in seeking help (47%). The majority of subjects in this survey could not be classified as "high risk." Therefore, clinicians should ensure that all young patients with asthma are aware of optimal maintenance management, can recognize deteriorating asthma, and follow a clear individualized crisis plan.

Aerosol delivery in lung disease.

Metered-dose inhalers are the preferred method of aerosol delivery under normal circumstances because of their convenient size, ease of use and better patient compliance. Where poor coordination exists a spacer device, breath-activated inhaler or powder inhalation should be used and if muscular weakness presents a problem a Haleraid should be tried. A clinical air pump with jet nebuliser is appropriate if these methods prove unsatisfactory; where wet aerosol has been shown to result in clearly superior effects; for very small children; and for the "brittle" asthmatic prone to sudden life-threatening attacks, especially patients living in isolated conditions. Regular checks on aerosol techniques and efficacy of therapy are important aspects of follow up and education of all patients with airflow obstruction.

Deaths from asthma in Victoria: a 12-month survey.

The circumstances surrounding the death of all patients who died from asthma in the State of Victoria over a 12-month period from May 1, 1986 were investigated. Data were collected using an interviewer-administered questionnaire as soon as practicable after registration of the death. In 168 cases asthma was considered to be the cause of death and adequate data were obtained in 163; 75 of these were male (74 over 60 years of age). Thirteen per cent had a history of trivial or mild asthma, 22% of moderate and 65% of severe asthma. Thirty-four per cent had not been limited at all or only by active sport, while 39% had had no previous hospital admission for asthma. In only 18% had there been a previous admission to an intensive care unit. Forty-seven per cent were taking inhaled beclomethasone or sodium cromoglycate regularly and 27% were taking corticosteroids by mouth regularly. Death occurred outside hospital in 150 of 163 subjects. In the final attack 58% had a sudden onset and collapsed within minutes, 20% were found dead and 27% had an acute progression of an established attack. Twenty-nine per cent of the deaths were assessed as preventable: preventable factors included inadequate assessment or therapy of prior asthma (35%), poor compliance with therapy (33%) and delay in seeking help (43%). As a significant number of subjects in this survey could not be classified as "high risk", it is important that clinicians ensure that all patients are aware of optimal maintenance management and have a clear individualized plan of what to do in the event of deteriorating asthma.

Do patients understand asthma? A community survey of asthma knowledge.

Four hundred and twenty-one subjects who attended metropolitan pharmacies in Melbourne that were selected at random were surveyed about the characteristics of, and their knowledge about, their asthma. An unexpectedly-high morbidity was found among 232 persons with asthma, who were aged between 16 years and 75 years. Forty per cent of subjects had been hospitalized at least once for asthma and 15% of subjects were taking maintenance corticosteroid agents by mouth. Twenty per cent of subjects currently were smoking cigarettes (15 cigarettes per day on average). When knowledge of asthma was examined by a questionnaire, the median score of questions that were answered correctly was less than 50% of the total. The best knowledge scores were associated with subjects: who had been exposed in the past to information about asthma; who had attended a private medical specialist; who were non-smokers; and who had achieved the highest levels of schooling. Among the serious misconceptions which were evident in the areas of use of medication were: that sustained-release theophylline agents acted quickly during acute attacks of asthma (62% of subjects); that antihistamine agents should be taken as soon as possible during an asthma emergency (72% of subjects); that six inhalations of beclomethasone were advisable during an asthma emergency (49% of subjects); that systemic corticosteroid agents were effective within 20 minutes of administration (87% of subjects); and that deaths of asthma usually were due to precipitous attacks without time for any intervention (73% of subjects). Only 42% of subjects considered that up to six puffs at once of a beta-agonist aerosol for an asthma emergency may be appropriate. The identification of such misconceptions is quite practical during routine consultations. The correction of such misconceptions may improve the morbidity and mortality that is due to asthma.

The efficacy of nedocromil sodium (Tilade) in asthma.

Nedocromil sodium is a new antiasthmatic drug with properties similar to sodium cromoglycate. We examined the efficacy of nedocromil sodium compared to placebo in 71 asthmatic patients in a three-centre double-blind parallel group study over 12 weeks. During the study the patients' maintenance inhaled corticosteroids were progressively withdrawn. Nedocromil sodium had an advantage over placebo in the number of withdrawals related to uncontrolled asthma, 14 and 24 respectively (p = 0.03). Changes in symptom scores, peak flow rates and bronchodilator use favoured nedocromil sodium occasionally during the study. The unusual taste of the active drug was reported frequently. Nedocromil sodium is more efficacious than placebo in asthma maintenance, but does not replace inhaled corticosteroids.

Alveolar proteinosis treated with a single bronchial lavage.

An acute febrile illness with respiratory failure and pulmonary infiltrates is a recognized accompaniment of many infective and inflammatory diseases. We report a case of pulmonary alveolar proteinosis, with secondary bacterial infection, that responded to a single pulmonary lavage and the elimination of occupational exposure to dust. In contrast to other interstitial lung diseases, therapy with corticosteroid or antibiotic agents alone was not appropriate. This report underlines the need for early, active intervention in diffuse lung diseases, and emphasizes the importance of obtaining a specific diagnosis in directing subsequent therapy.

A 4-week Australian multicentre study of nedocromil sodium in asthmatic patients.

The use of nedocromil sodium 4 mg q.i.d. in asthmatics with mildly unstable asthma induced by a reduction of their inhaled beclomethasone dipropionate dose was investigated in a double-blind, parallel group, placebo-controlled study. Compared with placebo, nedocromil sodium improved night-time and daytime asthma score, night-time and daytime bronchodilator use, and evening PEFR at some stage during the 4-week treatment. It is concluded that nedocromil sodium exerts a beneficial effect in chronic asthma.

The potential bronchodilator action of verapamil.

Although calcium antagonists such as verapamil are used primarily in cardiovascular disease, they appear to relax smooth muscle generally. Therefore, the possibility that verapamil might have bronchodilator properties was explored using the guinea-pig tracheal ring technique. Verapamil was found to produce considerable tracheal smooth muscle relaxation from a threshold concentration of 2 X 10(-7) M and with maximum effect at 10(-3) M. The responses to the contractile agonists histamine and prostaglandin F2 alpha and especially methacholine and serotonin were substantially reduced by prior administration of verapamil. Verapamil 2 X 10(-4) M was equally effective as isoprenaline 10(-8) M in producing 50% maximum direct relaxation but was more effective than isoprenaline as an antagonist of the contractile agonists, methacholine, histamine and serotonin, but not prostaglandin F2 alpha. Verapamil abolished the contractile responses to barium chloride. It is concluded that, although verapamil was not very potent as a direct bronchodilator, it could potentially be of prophylactic benefit in asthma because of its efficacy as an antagonist of common contractile agonists.

Respiratory disability in workers' compensation claimants.

This study was designed to examine whether claimants for compensation for work-related respiratory impairment due to chronic airflow obstruction exhibited greater symptoms of disablement than other patients with similar obstruction. It also sought evidence of bias, either towards or against the claimants, by the medical examiners. One hundred and twenty-eight subjects (68 claimants) with chronic asthma, chronic bronchitis, and emphysema were studied. There was a reasonable concordance of subjective judgements between patients and medical examiners in 81% of the disabled workers, and in 90% of the other medical group. Similarly, impairment of lung function (FEV1/VC ratio) in both groups was comparable at most levels of subjective disability. It was concluded that, in contrast to some previous reports, claimants for compensation for work-related chronic obstructive airway diseases did not tend to exaggerate their disabilities. This does not imply that the claimants' ailments were necessarily occupation-related.

Assisting the asthma patient in self management.

Patients with chronic illnesses seek out specific organisations not from dissatisfaction with their own doctor or in the hope of more modern treatment or a miracle cure but to learn as much as possible about their illness.