Are [[beta].sub.2]-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systematic review - Original Research

Journal of Family Practice, Nov, 2001 by John J. Smucny, Cheryl A. Flynn, Lorne A. Becker, Richard H. Glazier

The only trial that mentioned how well patients adhered to study medications (25) reported more than 95% compliance for both groups. Regarding co-interventions, 3 trials prohibited other antitussives (19,23,24); 3 trials allowed them and recorded their use as an outcome (20.21.25); and one trial did not mention co-interventions. (22) One trial prohibited the use of antibiotics (24); other trials comparing [[beta].sub.2]-agonists to placebo allowed the use of antibiotics at the discretion of the clinician (except as noted for the 1994 study by Hueston (21)). No trials were clearly sponsored by pharmaceutical manufacturers, but the medications were supplied free of charge by manufacturers in 3 studies. (19,22,24)

The quality of the trials varied from 2 to 4 on the Jadad scale (Table 1). The [kappa] score for reviewers' quality scores was 0.27, indicating only fair agreement. The majority of the disagreements related to different initial interpretations of the adequacy of blinding and description of withdrawals. These differences were resolved with further discussion.

Data Analysis

The clinical heterogeneity of the trials was so great that examining them as a single group did not seem reasonable. Therefore, we initially examined the trials as follows: (1) those in children, (2) those in adults comparing [[beta].sub.2]-agonists with placebo, and (3) those in adults comparing [[beta].sub.2]-agonists with erythromycin. We then combined the data from the trial that compared a [[beta].sub.2]-agonist with erythromycin with that from the other trials in adults in a secondary analysis.

Trials in Children

Neither trial involving children demonstrated any benefits from albuterol (Table 2). Combining the daily cough scores for days 1 to 3 for these trials revealed a trend toward worse scores in the group receiving albuterol. The results from the 2 trials were homogeneous.

Trials in Adults Comparing [[beta].sub.2]-agonists with Placebo

The results of the placebo-controlled trials in adults were mixed; one trial found no benefit from [[beta].sub.2]-agonists, and 3 found at least one benefit. Combining the daily cough severity scores for the 3 trials that included this outcome (20,22,24) showed a small non-significant trend toward improvement on all days. The results from the individual trials were heterogeneous for day 1 and homogeneous for the other days.

Combining data from the trials that examined persistence of symptoms after a full 7 days of treatment (20-22) yielded no significant difference in presence of cough or night cough (Table 4). Combined data also do not show a difference regarding the presence of a productive cough after 7 days or a difference regarding whether patients were working after 4 days. There was significant heterogeneity for 3 of the 4 dichotomous outcomes: cough, productive cough, and return to work.

Trials in Adults Comparing [[beta].sub.2]-agonists with Erythromycin

In the 1994 Hueston study, (21) patients given albuterol were less likely to have a cough or a productive cough after 7 days than those given erythromycin, but there were no differences in the presence of night cough after 7 days or in mean days until improvement in cough, well-being, or return to work or normal activities. When the data from this study are combined with that from the other adult trials, there are no significant differences regarding presence after 7 days of cough (RR=0.77; 95% confidence interval [CI], 0.54-1.09), productive cough (RR=0.66; 95% CI, 0.35-1.25), or night cough (RR=0.85; 95% CI, 0.57-1.26).