OBJECTIVE: Our goal was to determine whether b2-agonists improve the symptoms of acute bronchitis or acute cough in patients who do not have underlying pulmonary disease.
STUDY DESIGN: We performed a systematic review including meta-analysis.
DATA SOURCES: We included randomized controlled trials comparing b2-agonists with placebo or alternative therapies identified from the Cochrane Library, MEDLINE, EMBASE, conference proceedings, Science Citation Index, the System for Information on Grey Literature in Europe, and letters to manufacturers of b2-agonists.
OUTCOME MEASURED: We measured duration, persistence, severity or frequency of cough, productive cough, and night cough; duration of activity limitations; and adverse effects.
RESULTS: Two trials in children with cough and no obvious airway obstruction did not find any benefits from b2-agonists. Five trials in adults with cough and with or without airway obstruction had mixed results, but summary statistics did not reveal any significant benefits from b2-agonists. Studies that enrolled more wheezing patients were more likely to show benefits from b2-agonists, and in one study only patients with evidence of airflow limitation were more likely to benefit. Patients given b2-agonists were more likely to report tremor, shakiness, or nervousness than those in the control groups.
CONCLUSIONS: There is no evidence to support using b2-agonists in children with acute cough and no evidence of airflow obstruction. There is little evidence that the routine use of b2-agonists for adults with acute cough is helpful. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction, but this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with b2-agonists.
Acute bronchitis is characterized by cough associated with other symptoms of upper respiratory infection. Although this condition is self-limited, most patients feel ill, and many do not perform their usual activities. The optimal treatment for this common condition in patients who do not have underlying pulmonary disease is not clear. Clinicians often prescribe antibiotics,1,2 in spite of the fact that they are of little overall benefit.3,4 It is important to examine the effectiveness of alternative approaches.
b2-agonists have been proposed, because healthy patients have impaired airflow when infected with pathogens known to cause acute bronchitis.5-7 Also, cough is the primary symptom for some patients who have asthma,8 and many of these patients benefit from b2-agonists.9 b2-agonists are effective in reducing cough due to other causes, such as bronchoscopy10 and intravenous fentany1,11
We conducted this systematic review to determine whether b2-agonists are effective for patients who have acute bronchitis without underlying pulmonary disease. If b2-agonists are effective, then they should be more widely used; only a minority of US family physicians currently prescribe them for acute bronchitis.2,12
Methods
We attempted to locate all controlled trials that compared b2-agonists with placebo or an alternative treatment in patients older than 2 years who presented with acute bronchitis or acute cough without a clear etiology (eg, pneumonia, pertussis, or sinusitis). We included patients with acute cough, because the clinical definition of acute bronchitis is not standardized. Textbooks13-15 and clinician studies16,17 instruct that cough in association with an acute respiratory infection is required for a diagnosis; otherwise, there are differing criteria regarding the need for other symptoms and signs, such as dyspnea, abnormal chest findings, and sputum.
We searched MEDLINE (1966-2000), EMBASE (1974-2000), and The Cochrane Library (through August 2000) using the key words “bronchitis” or “cough”, together with the terms “adrenergic beta-agonist (exp),” “bronchodilator agents (exp),” “sympathomimetic (exp),” “albuterol,” “salbutamol,” “bitolterol,” “isoetharine,” “metaproterenol,” “pirbuterol,” “salmeterol,” “terbutaline,” “fenoterol,” “formoterol,” or “procaterol” (note that albuterol and salbutamol are the same compound). We also searched conference proceedings databases (Inside Conferences, 1993-99; Conference Papers Index, 1973-99); the System for Information on Grey Literature in Europe database (1980-2000); the reference lists of retrieved articles, review articles, and textbooks; and the Science Citation Index (1990-2000). Finally, we wrote to all US manufacturers of brand name b2-agonists. There were no language restrictions in our search.
Two investigators (C.F., J.S.) independently reviewed all the retrieved titles and abstracts. Studies selected by either investigator as possibly meeting the inclusion criteria were retrieved in their entirety. One investigator (J.S.) then deleted the journal of publication, title, authors, affiliations, and results sections of each study that met the inclusion criteria, and compiled a list of all the reported outcomes. The list of outcomes was forwarded to the other 3 investigators who independently, and then through discussion, determined which outcomes would be included in our review. The main criterion for selection was that the outcome should be directly important to patients. The same 3 investigators then graded the quality of each study using the 5-point Jadad scale, with points given for method of randomization (0-2), adequacy of blinding (0-2), and description of withdrawals (0-1).18 The Jadad scale is a validated, well-accepted, and frequently used quality assessment scale. Agreement on quality was assessed with a k score, and disagreements were resolved by discussion. Trials were excluded if all investigators agreed that the trial did not meet our inclusion criteria. The remaining articles in their entirety were then distributed to all investigators, each of whom independently extracted data for the selected outcomes. Disagreements were resolved by discussion. We attempted to contact authors to obtain missing data.