Regular inhaled salbutamol was better than as-needed salbutamol for asthma
ACP J Club. 1994 Nov-Dec;121:70. doi:10.7326/ACPJC-1994-121-3-070
Chapman KR, Kesten S, Szalai JP. Regular vs as-needed inhaled salbutamol in asthma control. Lancet. 1994 Jun 4;343:1379-82.
To compare regular use of inhaled salbutamol with as-needed use for asthma control and pulmonary function in adults with moderate-to-severe asthma.
4-week, single-blind, randomized crossover trial.
Asthma clinics in Canadian hospitals or academic-affiliated practices.
341 patients (mean age, 42 y; 218 women) met the American Thoracic Society criteria for the diagnosis of asthma and required daily treatment with inhaled β2-agonists, were clinically stable at time of enrollment, had not been treated with oral steroids during the preceding 30 days, and had forced expiratory volume at 1 second (FEV1) of ≥ 40% of predicted with ≥ 15% increase 30 minutes after inhalation of 200 mg of salbutamol. Patients with serious nonrespiratory illnesses and women of child-bearing potential were excluded. 313 patients (92%) completed the study.
Patients were randomly allocated to take salbutamol, 2 puffs (200 µg) 4 times/d, from a coded inhaler or matching placebo. Patients in both treatment arms took open-label salbutamol as needed. After 2 weeks, patients received the crossover treatment. The first 6 days of each 2-week period were a run-in or washout period. Using diary cards, patients recorded their peak expiratory flow rate (PEFR), asthma symptoms, and the number of as-needed salbutamol puffs.
Main Outcome Measures
Morning and evening PEFR and number of daytime and nighttime asthma episodes. 2 assessors, blinded to treatment assignment, categorized patients with respect to asthma control during the 2 periods. The reviewers rated each patient as the same or different during the 2 periods according to 6 sets of different decision criteria.
Patients taking regular salbutamol compared with as-needed salbutamol had fewer mean daytime and nighttime asthma episodes and took fewer supplementary salbutamol puffs (1.39 vs. 2.44, 0.50 vs. 0.65, and 1.14 vs. 2.35, respectively; P < 0.001 for all comparisons). Regardless of which set of criteria was used, patients taking regular salbutamol had better asthma control than patients taking as-needed salbutamol (P < 0.001). The groups did not differ for morning (336 L/min vs. 337 L/min) and evening (378 L/min vs. 373 L/min) PEFR.
Adults with moderate-to-severe asthma taking regular salbutamol had fewer asthma episodes and took fewer supplementary salbutamol puffs than those taking as-needed salbutamol.
Source of funding: Not stated.
For article reprint: Dr. K.R. Chapman, Asthma Centre of the Toronto Hospital, Suite 4-011, ECW, 399 Bathurst Street, Toronto, Ontario M5T 2S8. FAX 416-360-6456.
Recently, Sears and colleagues (1) reported that regular as opposed to as-needed fenoterol use was associated with poorer asthma control. The results of the study by Chapman and colleagues are very different; by all 6 clinical criteria, regular salbutamol use was superior to as-needed salbutamol use.
Several aspects of this trial, however, deserve mention with regard to the generalizability of the results. First, 80% of all participants were using anti-inflammatory inhalers (inhaled cromolyn or steroids), which they continued using during the course of the trial. Second, by virtue of the mean 64% predicted prebronchodilator FEV1 at baseline, these participants had moderate-to-severe asthma. Finally, the duration of the trial was only 4 weeks, a relatively short time for a trial of a chronic disease. The methods of the Sears study differed because it was of a longer duration (6 months on each treatment regimen), used fenoterol, and enrolled patients with milder asthma, fewer of whom were using anti-inflammatory inhalers.
Little question exists that airway responsiveness increases with β2-agonist monotherapy (2, 3). Although inhaled β2-agonists alone are not a satisfactory treatment for patients with moderate-to-severe asthma, this trial suggests that regular β2-agonist use in conjunction with anti-inflammatory medication is safe and may decrease symptoms. As noted by the authors, it still remains controversial whether the possible risk of regular β2-agonist use is worth the tradeoff of reduced symptoms. Any patient who uses short-acting inhaled β2-agonists more than 6 or 7 times during a 24-hour period (i.e., more than every 4 hours) should be instructed to call his or her physician immediately. As noted by the authors, the role of longer-acting β2-agonists, such as salmeterol and formoterol, needs to be carefully assessed in light of the enhanced potential for overdosage. Further clinical trials will be necessary to clearly define the role of β2-agonists in asthma care.
Scott Weiss, MD, MS
Harvard Medical School Boston, Massachusetts, USA