EFFECTS OF 22 MONTHS OF TREATMENT WITH INHALED CORTICOSTEROIDS AND OR BETA-2-AGONISTS ON LUNG-FUNCTION, AIRWAY RESPONSIVENESS, AND SYMPTOMS IN CHILDREN WITH ASTHMA

In a randomized double-blind multicenter clinical study, 116 children with asthma were randomly assigned to treatment with an inhaled beta-2-agonist (salbutamol 0.2 mg) plus an inhaled corticosteroid (budesonide 0.2 mg) three times a day (BA + CS) or to an inhaled beta-2-agonist (salbutamol 0.2 mg) plus a placebo three times a day (BA + PL). After a median follow-up time of 22 months, 26 patients receiving BA + PL (45%) had withdrawn from randomized treatment, mainly because of asthma symptoms, compared with three withdrawals in the patients receiving BA + CS (p < 0.0001). The FEV1, expressed as a percentage of the predicted value for age, sex, and height, showed an absolute increase of 7.0% after 2 months of BA + CS compared with a decrease of 4.0% after 2 months of BA + PL. This 11% difference in percent predicted FEV1 (96% confidence interval, 7 to 15%; p < 0.0001) was then maintained after a median follow-up period of 22 months. Postbronchodilator FEV1 showed an absolute increase of 3.7% predicted within 2 months in patients receiving BA + CS and an absolute decrease of 1.1% predicted in children receiving BA + PL (p = 0.0005). Thereafter, this difference between the two treatment groups was maintained. Average peak expiratory flow rate (PEFR) increased from baseline by 36.6 L/min in the BA + CS group compared with 3.7 L/min in the BA + PL group (p = 0.003). This difference then remained for the median follow-up time of 22 months. Mean airway responsiveness expressed as the provocative dose of histamine required to give a 20% fall in FEV1 increased from baseline to 4 months by 0.98 doubling doses in children receiving BA + CS compared with a decrease of 0.42 doubling doses in patients receiving BA + PL. This represents a difference of 1.4 doubling dose (95% confidence interval, 0.77 to 2.02; p < 0.0001), which became even greater with further follow-up and did not reach a plateau after the median follow-up period of 22 months. PEFR-variability expressed as the average standard deviation of dally measurements was reduced by 5.9 L/min within 2 months in patients receiving BA + CS (nearly one quarter in relative terms) compared with an increase of 1.6 L/min in those receiving BA + PL (p = 0.015). Thereafter, the difference was maintained. After 2 months of treatment the median number of days with symptoms remained 3 days per 2-wk period in the BA + PL group and decreased to 2 days in the BA + CS group. This difference increased to 3 day versus 1 day at 12 months (p = 0.016) and 4 days versus zero days after 22 months (p = 0.25). No serious side effects have been reported in either treatment group. This study provides strong evidence that inhaled corticosteroids are important in the long-term treatment of childhood asthma.