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 discordant results seen in the trials of adults may reflect different patient populations. Although the inclusion criteria were similar in these trials, more patients were wheezing on initial examination in the Hueston studies (21,25] than in the studies by Littenberg and coworkers (20) or Melbye and colleagues. (22) Wheezing in unforced expiration is a specific finding for airflow obstruction (28); and therefore, more patients in the Hueston trials (21,25) were likely to have had obstruction than in Littenberg and coworkers' study (20) (and since the lungs were auscultated in forced expiration in the latter trial, the actual number with airflow obstruction may have been even less than indicated). The fact that only the subgroup with airway obstruction improved with [[beta].sub.2]-agonists in the trial by Melbye and colleagues (22) reflects the possible importance of this baseline characteristic.

Limitations

Our review has some limitations. Although it includes all of the available data regarding the effectiveness of [[beta].sub.2]-agonists for patients with acute bronchitis or acute cough, the number of studies and total number of patients included are small. Therefore, our review has limited power to detect differences between patients who were and were not given [[beta].sub.2]-agonists. In the combined data of trials in adults, there was a trend toward improvements regarding cough, productive cough, night cough, and return to work, but these differences did not reach statistical significance. The midpoint estimates for the relative risk reductions range from 14% to 24% for these outcomes, but all overlap 0. There was also a clinically minor and statistically non-significant trend toward lower daily cough severity scores in patients randomized to the [[beta].sub.2]-agonists.

The studies were also all of a short duration. There is no information as to whether treatment with [[beta].sub.2]-agonists would alter outcomes beyond 3 to 7 days. This is an important omission, because many patients in these studies were still bothered by symptoms at the end of the trials.

Only 2 studies evaluated inhaled [[beta].sub.2]-agonists, which would currently be the most likely formulation used in adults and older children. Neither of these studies used spacing devices. The delivery of the medicine may have been suboptimal and resulted in less benefit than might have been seen had spacers been used.

Overall, the quality of the trials was fair to good. There may have been additional biases, however, because most of the trials had unequal distribution of co-interventions and did not record compliance with study medications. Also, even though the studies were all double-blinded, the fact that the majority of the patients in one trial knew which study medication they had been given indicates that the blinding may not have been adequate in these studies because of the taste or side effects of the study medications.

CONCLUSIONS

Our review highlights the gaps in evidence regarding the utility of [[beta].sub.2]-agonists in the treatment of acute cough and acute bronchitis in patients without underlying pulmonary disease. Although there is a possibility that these agents may be useful, additional data demonstrating benefit is required before they can be routinely recommended. There is a particular need for identifying clinical characteristics that can predict which patients might benefit. For example, there is a complete lack of data in children older than 2 years who have signs of airway obstruction. More evidence on the risk-benefit ratio of [[beta].sub.2]-agonists in adults with clinical signs of airflow limitation is also necessary. Additional areas of useful research would be in evaluating long-acting [[beta].sub.2]-agonists (because of ease of adherence), in evaluating the benefits of inhaled [[beta].sub.2]-agonists with spacing devices, and in comparing [[beta].sub.2]-agonists with other symptomatic treatments.