A randomized controlled trial of oral albuterol in acute cough

Journal of Family Practice, Jan, 1996 by Benjamin Littenberg, Mark Wheeler, David S. Smith

Acute cough is common in ambulatory practice and a significant source of concern and of disability days. The vast majority of patients presenting with acute cough do not require treatment for a specific underlying condition, such as asthma, pneumonia, or chronic obstructive pulmonary disease (COPD). Currently, the only generally administered treatments for adults are oral cough suppressants and antibiotics. Most coughing patients have no evidence of bacterial infection and thus do not benefit from antibiotic therapy.

Beta-agonist drugs are widely used in cough due to asthma and COPD. Asthma with cough as the sole symptom is well described and appears to respond well to beta-agonist therapy.[1] Beta-agonists increase the cough threshold to irritants in normal subjects[2] and stimulate mucociliary clearance.[3] A study of terbutaline in chronic "allergic" cough indicated that there was a significant improvement in daytime and nighttime coughing.[4] Salbutamol, the British name for albuterol, has been shown to be effective for nighttime coughing[5] but was reported to have little effect on severity or frequency of cough during the day. In this study, all the patients were thought to have "acute respiratory infection," but no mention was made of specific antibiotic treatment.

A prior randomized trial compared albuterol elixir with erythromycin for adults with acute bronchitis.6 Albuterol-treated patients were less likely to be coughing after 1 week and had no more side effects than did the antibiotic-treated group. This study did not include placebo controls. Two other studies compared inhaled albuterol to placebo in adults with bronchitis and found a significant reduction in coughing at 7 days[7] and an improvement in spirometry with a nonsignificant improvement in symptoms.[8]

We sought to confirm the results of prior studies[5,6] of the effects of oral beta-adrenergic agents on patients, symptoms in outpatient therapy of acute cough. We chose oral albuterol rather than an inhaled beta-agonist because it is less expensive and does not require extensive patient instruction to ensure that patients receive an effective dose.

Methods

We performed a randomized, double-blind, placebo-controlled trial of albuterol in ambulatory adults with acute cough. The trial was performed in the adult walk-in clinic at Dartmouth-Hitchcock Medical Center between October 1992 and May 1994. The study protocol and patient consent procedures were approved by the institutional review board.

Eligible patients included all adults with nonspecific bronchitis or acute cough of less than 4 weeks, duration. We excluded patients if they were pregnant; were at risk for cardiac arrhythmia by virtue of known cardiac disease or history of arrhythmia; used any form of systemic or inhaled corticosteroids during the week prior to presentation; had findings of lung consolidation or infiltrate on physical examination or radiograph; had been treated for asthma or COPD within the past 10 years; used any form of beta-agonist medication by any route during the week prior to presentation; used any tricyclic antidepressant or monoamine oxidase inhibitor; had a contraindication to beta-agonist therapy, eg, arrhythmia, allergy, recent myocardial infarction; or refused consent.

All eligible patients were evaluated by the faculty or house staff physician on duty in the clinic. Diagnostic studies, including radiographs, spirograms and analysis of blood, were performed at the discretion of the clinician. If the physician judged that antibiotics were indicated, erythromycin 333 mg by mouth three times daily for 7 days was prescribed. If other antibiotics or corticosteroids were indicated, the patient was excluded. Physicians prescribed dextromethorphan cough suppressants or codeine at their discretion.

Patients were stratified by antibiotic use and then randomly assigned to either albuterol or placebo. Each patient was issued a vial of identical-looking pills prepared by the study pharmacist. The vials were labeled with the instructions "Take one pill three times a day for seven days." The active pills contained albuterol sulfate 4 mg. The control pills contained only a calcium carbonate filler. Randomization was achieved by a computer-generated random number assigned to each vial of medicine in the pharmacy. Large boxes of vials were delivered to the clinic and thoroughly mixed. Separate boxes were maintained for patients on antibiotics and those not taking antibiotics. The clinic staff chose one vial from the proper box for each patient and recorded the vial number.

At study entry, the nurse and physician completed a data record on each patient recording identification data, vial number, demographics, and symptoms. Clinic staff instructed each patient to complete a daily diary of symptoms for 1 week after the visit and instructed patients on how to take the study medicine and to return the diary. A research assistant contacted each patient during the week as a reminder to complete the diary and again 1 week later if the diary had not been promptly returned.