Dose-dependent respiratory responses to inhaled corticosteroids in asthma

Abstract

It is commonly recommended that the dose of an inhaled corticosteroid (ICS) be increased when there is evidence of increased asthma severity. However, the dose-dependent responses to such an increase in ICS dose are difficult to quantify because of the relatively slow onset of ICS effects in the airways. This study explored the use of sequential quadrupling dose regimens and a range of endpoints to assess the response to the ICS budesonide in 21 subjects with mild asthma. In a randomized protocol, subjects inhaled increasing doses of budesonide (100, 400, 1600 μg/day), each dose being given for 1 or 2 weeks, followed by several outcome assessments. The researchers found a significant dose-dependent decrease in bronchial hyperreactivity (BHR), as assessed by adenosine-induced bronchoconstriction, somewhat more pronounced when the increased budesonide dose was given for a 2-week period. Use of increased dosages of budesonide was followed by increases in FEV1 and morning peak expiratory flow rate (PEFR); however, these changes in expiratory flow rates were small and were more variable than the changes in BHR. Changes in the evening PEFR, symptom scores, and reliever use of inhaled β-agonists were small and not ICS dose–related. The authors concluded that through use of a determination of BHR assessed by adenosine inhalation challenge, a clear-cut response to quadrupling increases in the inhaled budesonide dose could be detected in individuals with mild asthma. It is noteworthy, however, that this same investigative group has recently reported that a doubling of the dose of inhaled budesonide with worsening asthma symptoms in a patient self-management program was not associated with a reduced frequency of subsequent acute asthma exacerbations.