It is important to point out that some aspects of the study design were chosen to closely emulate what might happen in the normal clinical setting when a reduction in the dose of ICS is attempted, including the single-blind design and the use of different ICS products and doses. One could argue that some patients may be prone to report more severe clinical manifestations because they were informed that the ICS dose was reduced. However, this effect would be independent of the response to inhaled AMP or ENO levels and, therefore, should not have biased the study results. Furthermore, although our study was not done in a double-blind manner, the identification of exacerbations was performed by personnel blinded to the results of the AMP challenge and ENO determination.
Table 3—ORs for Failure of ICS Reduction
OR 95% CI p Value
Baseline
| PC20 s 400 mg/mL | 2.92 | 0.62-13.76 | > 0.05 |
| ENO > 15 ppb | 1.68 | 0.29-9.75 | > 0.05 |
| ENO > 20 ppb | 1.20 | 0.27-5.25 | > 0.05 |
| ENO a 30 ppb | 1.13 | 0.26-5.02 | > 0.05 |
| PC20 s 400 mg/mL plus ENO | 8.17 | 1.60-41.64 | < 0.05 |
| a 15 ppb | |||
| PC20 s 400 mg/mL plus ENO | 5.25 | 1.11-24.92 | < 0.05 |
| a 20 ppb | |||
| PC20 s 400 mg/mL plus ENO | 1.89 | 0.36-9.97 | > 0.05 |
| a 30 ppb
Changes from baseline* |
|||
| APC20 a 1 doubling | 3.50 | 0.75-16.27 | > 0.05 |
| concentration | |||
| AENO a 10 ppb | 1.89 | 0.36-9.97 | > 0.05 |
*Changes from the run-in period to the visit performed 2 weeks after the reduction of ICS.
From our results, it seems that reducing the dose of ICS is possible in many asthmatic patients in a stable phase of the disease; however, despite recommendations about the need for stepwise reduction in ICS therapy as part of long-term management, algorithms about how to do this are currently lacking. A primary goal of this investigation was to evaluate the utility of the determination of AMP responsiveness and ENO levels as markers for safely reducing the dose of ICS in patients with asthma well controlled with a moderately high dose of ICS. Our study indicates that having both bronchoconstriction in response to AMP and ENO levels of at least 15 ppb at baseline is a predictor for failure of ICS reduction.
To the best of our knowledge, there are no studies that have investigated the utility of the determination of AMP responsiveness as a marker for safety reducing the dose of ICS. At baseline, having bronchocon-striction in response to AMP was not a significant predictor for failure of ICS reduction. Our findings are supported by Leuppi and coworkers, who demonstrated that having airway hyperresponsiveness to mannitol (an indirect bronchoconstrictor) was not a significant predictor for failure of ICS reduction.