Long-acting β2-agonists in the treatment of acute exacerbations of COPD

Objective: To evaluate the acute bronchodilating effect of cumulative doses of formoterol administered via Turbuhaler(TM) or salmeterol administered via pressurised metered-dose inhaler (pMDI) in patients with mild acute exacerbations of chronic obstructive pulmonary disease (COPD) to determine if these drugs might be used in this condition. Design: This was a randomised, double-blind, double-dummy, crossover study taking place over two consecutive days. Patients and setting: 30 patients attending our outpatient clinics with mild acute exacerbations of COPD (Anthonisen exacerbation type I or II), and who were willing to participate, were recruited. Interventions: A dose-response curve to salmeterol pMDI (25 mug/inhalation) or formoterol Turbuhaler(TM) (12 mug/inhalation) was constructed using one inhalation, one inhalation, and two inhalations, i.e. a total cumulative dose of metered salmeterol 100mug or formoterol 48mug on two consecutive days. After baseline measurements, dose increments were given at 30-minute intervals with measurements being made 25 minutes after each dose. Oral bronchodilators were not permitted during the study. Short-acting inhaled beta(2)-agonists were permitted soon after each test when required. All patients received treatment with an oral antibiotic (amoxicillin/clavulanic acid or levofloxacin) and an inhaled steroid (budesonide 400mug or fluticasone 250mug twice daily). Main outcome measures: The highest forced vital capacity (FVC), inspiratory capacity (IC) and forced expiratory volume in one second (FEV1) values obtained from one or other of the curves were kept for analysis. We also measured oxygen saturation by pulse oximetry (SpO(2)) and heart rate (HR). The maximum FEV1 value during the dose-response curve to formoterol or salmeterol was chosen as the primary outcome variable to compare the two treatments. Results: Both formoterol and salmeterol induced a large and significant (p < 0.001) dose-dependent increase in FEV1, FVC and IC. There was no significant difference between the FEV1 values (p =0.081), the FVC values (p=0.085) and the IC values (p = 0.111) after formoterol 48 mu g or salmeterol 100 mu g. Neither HR nor SpO(2) changed significantly (p > 0.05). Conclusions: Our results suggest that cumulative doses of long-acting beta(2)-agonists may improve lung function in patients with mild acute exacerbations of COPD although we cannot advocate their use in the initial therapy of an acute exacerbation because much fundamental information is still lacking.