When asthma control deteriorates, a common strategy is to double or quadruple the maintenance dose of inhaled steroids. In stable patients, this technique results in modest improvements in spirometry and peak flow results, but the effect in patients who are clinically deteriorating has not been established. Harrison and colleagues studied the ability of prompt doubling of the dose of inhaled steroids to reduce the severity and duration of asthma exacerbations.
They studied 390 adult British primary care patients who used inhaled corticosteroids for treatment of asthma. Participants were required to have used oral corticosteroids or to have temporarily doubled their dose of inhaled corticosteroid to treat an exacerbation at least once in the previous year. Patients with unstable asthma in the two weeks before entering the study and those with more than a 10pack-year smoking history were ineligible for the study. During the two-week run-in period, patients underwent spirometry and recorded daily symptoms and morning peak-flow measurements. Patients were asked to continue usual treatment and to use the study inhaler for 14 days if the morning peak flow fell by 15 percent or their daytime symptom scores increased by one point from the median values established during the run-in period.
After stratification for severity of asthma, patients were randomly issued active or placebo inhalers. Use of the active inhalers doubled the dose of the usual corticosteroid for individual patients. A range of inhalers was prepared so that active and placebo inhalers matched the existing treatment for each patient. Patients recorded morning peak flow and symptom scores for 28 days after beginning the additional treatment. If the clinical condition deteriorated or peak flow fell by 40 percent or more, patients were treated with oral corticosteroids. The primary study outcome was the proportion of participants requiring oral steroids. Other outcomes included maximal fall in peak flow, increase in symptom scores, and time until return to median values of peak flow and symptom scores.
Of the 192 patients who were allocated to the study inhaler, 175 completed the study, and 110 used the inhaler during the study. In the placebo group, 97 of 198 patients used the inhaler. In the treatment group, 22 (11 percent) used oral corticosteroids compared with 24(12percent) in the placebo group. The reasons for beginning oral steroid therapy were advice from the primary care physician (24 patients), symptoms of deteriorating asthma control (12 patients), and a fall in peak flow of at least 40 percent (10 patients). Although doubling the dose of inhaled corticosteroid was associated with a small, non-significant reduction in the maximum fall in peak flow, the two groups did not differ in the lowest peak flow recorded or changes in symptom scores. In addition, no effect was noted in the time for symptom scores or peak flow measurements to return to baseline values. These results were unchanged when patients with different severities of asthma were analyzed as independent groups.
The authors conclude that doubling the dose of inhaled corticosteroids had little effect on outcomes of asthma exacerbations in patients using maintenance inhaled steroids. They speculate that a fourfold or greater increase in steroid dose may be necessary for clinical effect.