Are b2-agonists Effective Treatment for Acute Bronchitis or Acute Cough in Patients Without Underlying Pulmonary Disease? A Systematic Review

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Original Research

Are b2-agonists Effective Treatment for Acute Bronchitis or Acute Cough in Patients Without Underlying Pulmonary Disease? A Systematic Review

J Fam Pract. 2001 November;50(11):945-951

References

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Adverse Effects

In the trials in children, 11% of the patients given albuterol had shaking or tremor versus 0% given placebo or only dextromethorphan (RR=6.76; 95% CI, 0.86-53.18; NNT=9; 95% CI, 5-100); the results were homogeneous. There were no differences regarding other adverse effects in the trials in children. In the adult trials, patients given b2-agonists were more likely to report tremor, shaking, or nervousness; the percentage of patients having these side effects in the 3 trials that reported specific side effects ranged from 35% to 67% versus control rates of 0% to 23% (RR=7.94; 95% CI, 1.17-53.94; NNT=2.3; 95% CI, 2-3). These data are from the trials that used inhaled fenoterol and oral albuterol.^20,22,25 However, in the 1991 Hueston study,²⁵ only 9% of the patients given inhaled albuterol reported any side effects; therefore, there is considerable heterogeneity among the results of the individual trials. There were no significant differences regarding other adverse effects between the b2-agonist group and control groups as a whole, but the trial comparing albuterol with erythromycin noted more gastrointestinal side effects in the erythromycin group (NNT=3; 95% CI, 2-8).

Subgroup Analyses

In the study by Melbye and colleagues,²² the subgroup of patients with evidence of airway obstruction (defined as wheezing on initial examination, a forced expiratory volume in 1 second of <80% predicted, or a positive response to a methacholine challenge test) who were given fenoterol had lower symptom scores beginning at day 2 than those in this subgroup who were given placebo. This was also true for the smaller subgroup that just had wheezing, but no difference was noted for patients with a normal lung examination. No other trial did a subgroup analysis limited to patients with evidence of airflow obstruction. The 1994 Hueston study²¹ reported that among patients given albuterol, those with wheezing were slightly less likely to be coughing after 7 days than those without wheezing, but the difference was not statistically significant.

Melbye and coworkers²² found that patients who smoked or had also received antibiotics had greater reductions in total symptom scores on day 7 if given fenoterol. Smokers had similar responses to nonsmokers in the studies by Hueston.^21,25 Littenberg and colleagues²⁰ found that patients given erythromycin trended toward lower cough severity scores if given albuterol instead of placebo, and patients not given erythromycin showed a trend toward higher scores if given albuterol. The 1994 Hueston study²¹ reported that the differences between the groups given and not given albuterol persisted after stratification by erythromycin use.

Discussion

The findings from our review do not support the routine use of b2-agonists for patients who do not have underlying pulmonary disease and present with an acute cough or acute bronchitis. These results must be interpreted in light of the patients that were enrolled in the trials. In particular, because the 2 trials in children excluded patients who were wheezing, the utility of b2-agonists in children with acute cough and evidence of airway obstruction is unknown. b2-agonists do lead to modest short-term improvements in clinical scores in children younger than 2 years who have bronchiolitis.²⁷

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 coworkers²⁰ or Melbye and colleagues.²² Wheezing in unforced expiration is a specific finding for airflow obstruction²⁸; and therefore, more patients in the Hueston trials^21,25 were likely to have had obstruction than in Littenberg and coworkers’ study²⁰ (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 b2-agonists in the trial by Melbye and colleagues²² 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 b2-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 b2-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 nonsignificant trend toward lower daily cough severity scores in patients randomized to the b2-agonists.