Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial.

BACKGROUND: Asthma guidelines recommend that long-acting inhaled beta-agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid. We studied the safety and efficacy of the long-acting beta-agonist formoterol compared with terbutaline, each taken as needed, in patients with moderate to severe asthma. METHODS: Patients were taking an inhaled corticosteroid (mean dose 870 microg daily) and had a forced expiratory volume in 1 s (FEV1) of at least 50% predicted (mean 74%). Those requiring an inhaled beta-agonist three to eight times a day during the study run-in period (362 of 621 who started) were randomly assigned formoterol 4.5 microg or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 microg and 6 mg, respectively, for 12 weeks in a double-blind, parallel-group study. Analyses were by intention to treat. FINDINGS: The 362 randomised patients (157 men, 205 women) had a mean age of 47 years. Patients taking formoterol had a longer time to their first severe asthma exacerbation (relative-risk ratio 0.55 [95% CI 0.34-0.89]), took fewer inhalations of study drug, and had larger increases in FEV1 (5%) and morning and evening peak expiratory flow (mean difference in increase 11 L/min and 8 L/min) than those taking terbutaline. No safety issues were identified. INTERPRETATION: When taken as needed, formoterol 4.5 microg provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment. Safety studies should be extended to a wider population of patients with asthma.

[Oxygen therapy of patients with chronic obstructive pulmonary disease reduces the development of pulmonary hypertension]. / Oksygenbehandling av pasienter med kronisk obstruktiv lungesykdom reduserer utvikling av pulmonal hypertensjon.

The development of secondary pulmonary hypertension in patients with chronic obstructive pulmonary disease worsens their prognosis; oxygen therapy seems to improve prognosis in these patients. We measured the effect of oxygen therapy on mean pulmonary artery pressure in four women and four men aged 64 to 82 years (average 73 years) with chronic obstructive pulmonary disease. A right cardiac catheterisation was performed before and on average 11 months (8-16 months) after start of oxygen therapy. The mean pulmonary artery pressure decreased on average 5 mm Hg, from 24 to 19 mm Hg. As prognosis seems to be associated with pulmonary artery pressure, more patients with chronic obstructive pulmonary disease should be evaluated for oxygen therapy.

Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients.

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.

Comparison of oral bambuterol and inhaled salmeterol in patients with symptomatic asthma and using inhaled corticosteroids.

Salmeterol inhaled twice-daily is now being used more frequently as additional treatment in asthma insufficiently controlled by inhaled corticosteroids. We compared oral bambuterol in a dose of 20 mg taken once daily in the evening with inhaled salmeterol at 50 microgram taken twice daily in 126 asthmatic patients (60 bambuterol, 66 salmeterol) aged 18 to 74 yr who were treated for at least 4 wk with inhaled corticosteroids at a constant dose of 400 to 2,000 microgram/d or with oral corticosteroids at /= 15% overnight decrease in peak expiratory flow (PEF) on 3 of the preceding 7 d, in order to be randomized into this double-blind, double dummy, multicenter parallel group study (2-wk run-in period and 6 wk of treatment). There was no significant difference between bambuterol and salmeterol in morning change from baseline in PEF (p = 0.53). The median increases in morning PEF were 50 L/min for bambuterol and 55 L/min for salmeterol. Other variables (evening PEF, percent of overnight decrease in PEF, number of awakenings, percent of nights with an awakening, number of puffs of rescue medication, asthma symptoms during the day and night, and mean tremor score) also showed no significant difference between bambuterol and salmeterol. Both treatments, at the doses given, were well tolerated. Once-daily oral bambuterol is a convenient, effective, and less expensive alternative to twice-daily inhaled salmeterol for treating nocturnal asthma.