ADDITION OF ANTICHOLINERGIC SOLUTION PROLONGS BRONCHODILATOR EFFECT OF BETA(2) AGONISTS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

A randomized, double-blind, placebo-controlled clinical trial was desi gned to assess the safety, efficacy, and duration of the bronchodilati on resulting from the addition of 500 mu g of ipratropium bromide (Atr ovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution . A total of 195 patients (63% men, average age 64 years) with >10 pac k-year smoking histories and stable, moderate-to-severe chronic obstru ctive pulmonary disease (COPD; forced expiratory volume in 1 second [F EV(1)] 1.02 liter, 38.8% predicted) from eight university-affiliated c hest clinics in seven U.S. cities were enrolled into the study. Asthma , rhinitis, and eosinophilia were exclusions, as was daily use of >10 mg of prednisone (or 20 mg on alternate days). There was a 8-week stab ilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rate s, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having be en off theophylline for 24 hours and beta(2)-agonists for 12 hours and performed a baseline spirometry. They then received their morning sma ll volume nebulizer treatment of albuterol to which was added either 5 00 mu g of ipratropium bromide or a saline placebo. Spirometry was rep eated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 8-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pul monary symptoms and adverse effects every 14 days. The 8-hour spiromet ry was repeated on test day 43 and finally on test day 85. Primary dat a evaluated were the peak increase in FEV(1) and the area between the FEV(1) baseline value and the 8-hour FEV(1) curve. Similar calculation s were made for forced vital capacity (FVC) and 25-75% forced expirato ry flow (FEF(25-75%)) On test day 1 the peak increase in FEV(1) for th e ipratropium bromide+albuterol subjects was 26% greater than those on placebo+albuterol (p <0.003). The area under the 8-hour FEV(1) curve was 64% greater in those given ipratropium bromide on test day 1 (p <0 .0002). Similar increases were seen in FVC and FEF(25-75%). The peak i mprovements in FEV(1) and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would sugge st that ipratropium bromide inhalation solution should be considered f irst-line therapy for those patients with COPD requiring small volume nebulizer treatments.