ABSTRACT
OBJECTIVES: Formoterol, a beta(2) agonist with a rapid onset of effect and long duration of action, can be used as maintenance and reliever medication for asthma and COPD. We compared the pulmonary and extra-pulmonary effects of cumulative doses of formoterol and salbutamol in patients with COPD to assess efficacy and safety. METHODOLOGY: In a randomized, double-blind, cross-over study, 12 patients with moderate to severe COPD inhaled, via Turbuhaler, 10 doses of formoterol (total metered dose, 120 microg, equivalent to a 90- microg delivered dose), salbutamol (total metered dose 2000 microg) or placebo at 2-min intervals on separate days. The effects on lung function (FEV(1) and PEF), heart rate, blood pressure, oxygen saturation, corrected QT interval (QTc), T-wave height and plasma potassium were assessed before each dose, 15 min after each dose, and at half-hourly intervals for 3 h following the final dose. RESULTS: Inhalation of formoterol or salbutamol resulted in significant improvement in lung function (measured 30 min after the last dose) when compared with placebo. There were no clinically important or statistically significant changes in heart rate, QTc, T-wave height, plasma potassium, oxygen saturation, or systolic and diastolic blood pressures with formoterol or salbutamol. One patient developed ventricular trigeminy after both formoterol and salbutamol. She had had ventricular ectopics on her screening electrocardiogram. CONCLUSION: Formoterol and salbutamol both produced significant improvement in lung function and were similarly well tolerated in high doses, as might be taken by a patient for relief of COPD symptoms.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Albuterol/pharmacology , Ethanolamines/pharmacology , Pulmonary Disease, Chronic Obstructive/drug therapy , Adrenergic beta-Agonists/administration & dosage , Adrenergic beta-Agonists/therapeutic use , Aged , Albuterol/administration & dosage , Albuterol/therapeutic use , Blood Pressure/drug effects , Cross-Over Studies , Double-Blind Method , Ethanolamines/administration & dosage , Ethanolamines/therapeutic use , Female , Forced Expiratory Volume , Formoterol Fumarate , Heart Rate/drug effects , Humans , Male , Middle Aged , Peak Expiratory Flow Rate , Pulmonary Disease, Chronic Obstructive/physiopathologyABSTRACT
OBJECTIVE: There is epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of atopy and/or asthma. Delipidated, deglycolipidated and arabinogalactan-depleted autoclaved Mycobacterium vaccae (delipidated acid-treated M. vaccae) has been shown to suppress allergen-induced airway eosinophilia in mice. METHODOLOGY: Thirty-seven adults with stable moderately severe asthma who were skin prick test-positive to house dust mite were randomized to receive two doses 2 weeks apart of delipidated acid-treated M. vaccae (first dose 0.4 mg and second dose 0.8 mg) or phosphate buffered saline, given as drops intranasally. Safety, tolerability and markers of asthma severity (including peak flow, FEV1, major and minor exacerbations, symptom scores and beta-agonist use), and nasal symptom scores, blood eosinophil and IgE levels were monitored for 8 weeks. RESULTS: Delipidated acid-treated M. vaccae was safe and well tolerated although there was an occasional mild local reaction. There were no statistically significant differences between the treatment group and placebo for any of the outcome variables. CONCLUSIONS: There is a requirement to elucidate the reasons why mycobacterial-based vaccines have not shown equivalent efficacy in human trials compared with animal models. The role of factors such as duration of disease, route of administration and the active component of mycobacteria need to be addressed.
Subject(s)
Asthma/therapy , Bacterial Vaccines/therapeutic use , Mycobacterium/immunology , Administration, Intranasal , Adolescent , Adult , Double-Blind Method , Humans , Least-Squares Analysis , Linear Models , Middle Aged , Pilot Projects , Vaccines, InactivatedABSTRACT
BACKGROUND: Intravenous magnesium can cause bronchodilation in treatment of severe asthma, however its effect by the nebulised route is uncertain. We aimed to assess the effectiveness of isotonic magnesium sulphate as an adjuvant to nebulised salbutamol in severe attacks of asthma. METHODS: We enrolled 52 patients with severe exacerbations of asthma presenting to the emergency departments at two hospitals in New Zealand. A severe exacerbation was defined as a forced expiratory volume at 1 s (FEV(1)) of less than 50% predicted 30 min after initial administration of 2.5 mg salbutamol via nebulisation. In this randomised double-blind placebo-controlled trial patients received 2.5 mg nebulised salbutamol mixed with either 2.5 mL isotonic magnesium sulphate or isotonic saline on three occasions at 30 min intervals. The primary outcome measure was FEV(1) at 90 min. Analysis was per protocol. FINDINGS: At 90 min the mean FEV1 in the magnesium group was 1.96 L (95% CI 1.68-2.24) and in the saline group 1.55 L (1.24-1.87). The difference in the mean FEV(1) between the magnesium and saline groups was 0.37 L (0.13-0.61, p=0.003). INTERPRETATION: Use of isotonic magnesium as an adjuvant to nebulised salbutamol results in an enhanced bronchodilator response in treatment of severe asthma.
