Source: DGNews  |  Posted 8 years ago

By Peggy Peck

ORLANDO, FL -- November 3, 2003 -- Albuterol tolerance, rather than worsening disease, may explain serial decreases in postbronchodilator forced expiratory volume at 1 second (FEV1) in patients with chronic obstructive pulmonary disease (COPD), according to a retrospective study of data from two comparative trials of albuterol and ipratropium.

The finding was presented here October 29th at CHEST, 2003, the Annual Scientific Assembly of the American College of Chest Physicians.

Sammy C. Campbell, MD, Veterans Administration Hospital, Tucson, Arizona, said albuterol tolerance was previously described in asthma.

"We don't know why FEV1 appears to decline, then plateau at about a month, but we have seen this in asthma as well," he said. Tolerance was not, however, observed among patients treated with ipratropium, he added.

Dr. Campbell and colleagues evaluated spirometric responses to albuterol bronchodilators to determine if tolerance developed. They analyzed data from two double blind, parallel-group 85-day multicenter studies of albuterol, ipratropium or the combination of both in COPD patients.

The analysis was confined to data from 277 patients taking albuterol and 283 patients taking ipratropium. Before the trials, about 80% of patients were on albuterol and all patients were on three active drugs at enrollment.

Spirometry was measured pre- and serially post-study drug over 8 hours on days 1, 29, 57, and 85. The researchers used analysis of covariance to determine persistence of bronchodilation with Day 1 baseline as the covariate. The response on each test day was compared to the first test day. Only patients with Day 85 data were included.

Mean Day 1 pre-drug FEV1 in the albuterol group was 0.91L and in the ipratropium group it was 0.91L.

On Day 1, mean peak improvement and normalized area under the curve from 0 to 4 hours (AUC 0-4 ) and AUC 0-8 hour responses for albuterol were 0.33, 0.21, and 0.15 L. For ipratropium, the respective responses were 0.27, 0.17, and 0.12 L.

At Day 29, peak FEV1 had declined by 12.1% and this peak level was unchanged at Day 85. Likewise, AUC 0-4 declined by 17.9% at Day 29 and 8 hour AUC was 21.5% lower at Day 29. At 4 and 8 hours, AUC in the albuterol group declined by 16.7% and 22.3% from Day 1, Dr. Campbell said. By contrast, in the ipratropium arm, the Day 29 peak level increased by 7.4%, and AUC at 4 hours was 12.1% greater, while at 8 hours it was 8.3% greater than at Day 1. On Day 85, the peak level, AUC 0-4 and AUC 0-8 were 7.4%, 7.6%, and 7.3% higher, respectively, in the ipratropium group, he said.

The declines in the albuterol arm were significant at P < .01, but the difference in the ipratropium arm did not reach significance.

The study was funded by Boehringer Ingelheim.

[Study title: Tolerance to the Bronchodilating Effects of