Are b2-agonists Effective Treatment for Acute Bronchitis or Acute Cough in Patients Without Underlying Pulmonary Disease? A Systematic Review
Summary statistics were calculated using Review Manager 4.1 software (Update Software, Oxford, England). We used fixed effects models for outcomes without statistically significant heterogeneity (at P <.10) and random effects models for outcomes with significant heterogeneity. For dichotomous outcomes, we reported relative risks (RRs), absolute risk reductions, and numbers needed to treat (NNTs), and for continuous outcomes, standardized mean differences (SMD). We considered a level of P less than .05 to be statistically significant.
Results
Included Studies
The major characteristics of the trials are shown in Table 1. We included 6 controlled trials comparing b2-agonists and placebo,19-24 and one trial comparing a b2-agonist with erythromycin.25 A trial comparing a b2-agonist with placebo in children26 was excluded because all participants had recurrent cough and the mean duration of cough (8 weeks) was much longer than the maximum of 30 days used in the other trials.
All trials enrolled patients that presented to primary care settings. The stated diagnoses were “acute bronchitis,”21,22,25 “acute cough,”19,20 and “acute transient cough.”23,24 Both trials in children excluded participants with abnormal lung examinations19 or “with bronchial obstruction needing bronchodilating medication.”23 None of the adult trials excluded patients with wheezing; the percentage with wheezing ranged from 20% to 44% in the 4 trials that mentioned it. All adult trials included both smokers an nonsmokers.
The only trial that mentioned how well patients adhered to study medications25 reported more than 95% compliance for both groups. Regarding co-interventions, 3 trials prohibited other antitussives19,23,24 ; 3 trials allowed them and recorded their use as an outcome20,21,25 ; and one trial did not mention co-interventions. 22 One trial prohibited the use of antibiotics24 ; other trials comparing b2-agonists to placebo allowed the use of antibiotics at the discretion of the clinician (except as noted for the 1994 study by Hueston21). 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 k 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 b2-agonists with placebo, and (3) those in adults comparing b2-agonists with erythromycin. We then combined the data from the trial that compared a b2-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 Table 3. The results from the 2 trials were homogeneous.
Trials in Adults Comparing b2-agonists with Placebo
The results of the placebo-controlled trials in adults were mixed; one trial found no benefit from b2-agonists, and 3 found at least one benefit. Combining the daily cough severity scores for the 3 trials that included this outcome20,22,24showed a small nonsignificant 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 treatment20-22 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 b2-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).
