Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids

To determine predictors for failed reduction of inhaled corticosteroids (IC S), in 50 subjects with well-controlled asthma (age 43.7 [18-69]; 22 males) taking a median dose of 1,000 mug ICS/d (100-3,600 mug/d), ICS were halved every 8 wk. Airway hyperresponsiveness (AHR) to a bronchial provocation te st (BPT) with histamine was measured at baseline. AHR to BPT with mannitol, spirometry, exhaled nitric oxide (eNO), and, in 31 subjects, sputum inflam matory cells were measured at baseline and at monthly intervals. Thirty-nin e subjects suffered an asthma exacerbation. Seven subjects were successfull y weaned off ICS. Using a Kaplan-Meier survival analysis, the significant p redictors of a failure of ICS reduction were being hyperresponsive to both histamine and mannitol at baseline (p = 0.039), and being hyperresponsive t o mannitol during the dose-reduction phase of the study (p = 0.02). Subject s older than 40 yr of age tended to be at greater risk of ICS reduction fai lure (p = 0.059). Response to mannitol and percentage sputum eosinophils we re significantly greater before a failed ICS reduction than before the last successful ICS reduction, whereas there were no significant differences in symptoms, spirometry, or eNO. These findings suggest that documentation of patient's AHR or sputum eosinophils may he useful in guiding the reduction of ICS doses.