Beta2 agonists have been the mainstay of therapy in patients with acute asthma, mainly because of efficacy and rapid onset of action. Ipratropium bromide is an anti-cholinergic bronchodilator that acts more slowly than the beta agonists but has a longer duration of effect. It has been used most commonly in patients with chronic obstructive pulmonary disease, but results of several studies have suggested a synergistic benefit when ipratropium is used in combination with a beta agonist. Lanes and colleagues conducted a pooled analysis of three randomized double-blinded trials that evaluated the effectiveness of a combination of albuterol and ipratropium in the treatment of acute asthma.
The trials were conducted in the United States, Canada and New Zealand. Study subjects were between 18 and 55 years of age and were diagnosed with acute asthma using American Thoracic Society criteria. In addition, study subjects were required to have a smoking history of less than 10 pack-years and a baseline forced expiratory volume in one second (FEV1) of less than 70 percent of normal predicted value.
The patients were randomized to receive 3.0 mg of nebulized albuterol sulfate solution (2.5 mg of albuterol base plus 0.5 mg of saline solution) or 2.5 mg of albuterol plus 0.5 mg of ipratropium bromide. The treatments were administered at baseline and repeated after 90 minutes. The patients in the Canadian and New Zealand studies also received one dose of parenteral corticosteroid. Spirometry was performed at baseline and at 45 minutes and 90 minutes after treatment. The primary outcome was a change in FEV1 from baseline. After 90 minutes, the patients were admitted to the hospital or discharged with arrangement for 24-hour follow-up.
A total of 1,064 patients were enrolled in the three trials, with essentially an equal number randomized to treatment with albuterol alone or to treatment with albuterol with ipratropium bromide. The groups did not differ significantly in regard to baseline FEV1, recent asthma therapies or demographics.
The patients who received combination therapy had a mean improvement in FEV1 of 572 mL at 45 minutes compared with those receiving only albuterol, who had a mean improvement of 528 mL. At 90 minutes the combination group had a mean improvement of 677 mL in FEV1 compared with the albuterol group, which had a mean improvement of 630 mL in FEV1. The presence of an upper respiratory tract infection was the best predictor of response to combination therapy; these patients had greater overall improvements in FEV1 (83 mL at 45 minutes and 105 mL at 90 minutes) than those receiving only albuterol. In addition, patients who received combination therapy had an 8 percent lower risk of requiring additional asthma treatment, a 16 percent lower risk of asthma exacerbation and a 20 percent lower risk of needing hospitalization.
The authors conclude that adding ipratropium bromide to albuterol in the treatment of acute asthma appears to improve lung function and lowers the risk of further asthma exacerbation and subsequent hospitalization. However, the mean improvements in the FEV1 were relatively small, and further trials to determine additional clinical outcomes are needed.