Airway responsiveness to adenosine 5'-monophosphate and exhaled nitric oxide measurements: Predictive value as markers for reducing the dose of inhaled corticosteroids in asthmatic subjects

To investigate the utility of the determination of airway responsiveness to inhaled adenosine 5'-monophosphate (AMP) and exhaled nitric oxide (ENO) levels as markers for safely reducing the dose of inhaled corticosteroids (ICS) in patients with asthma well controlled with a moderately high ICS dose. A total of 37 patients with asthma well controlled for at least 3 months by treatment with a moderately high ICS dose (beclomethasone dipropionate, 500 to 1,000 microg or equivalent daily) were included in the study. Patients were treated for a 2-week run-in (baseline) period with their usual dose of ICS. For the next 12 weeks, patients were treated with ICS at half the previous dose, maintaining the same inhalation device. At the end of the baseline period and after 2 weeks, 8 weeks, and 12 weeks of treatment with a reduced dose of ICS, measurements were made in the following order: ENO, spirometry, and AMP challenge. Furthermore, patients completed a diary twice daily recording peak expiratory flow, daytime and nighttime symptoms, and use of rescue albuterol. Ten patients had an asthma exacerbation. Using a Kaplan-Meier survival analysis, the significant predictors of a failure of ICS reduction were having both bronchoconstriction in response to AMP and ENO levels > or = 15 parts per billion (ppb) at baseline (p = 0.006), as well as having both bronchoconstriction in response to AMP and ENO levels > or = 20 ppb at baseline (p = 0.033). Having a decrease in the provocative concentration of AMP causing a 20% fall in FEV(1) of at least one doubling concentration 2 weeks after the dose of ICS was halved was a borderline significant predictor for failure of ICS reduction (p = 0.062). These observations suggest that in asthmatic patients well controlled with ICS, the determination of AMP responsiveness and ENO levels may be useful to identifying those subjects whose condition will or will not deteriorate when the dose of ICS is reduced.