Università Degli Studi di Catania, Catania, Italy
Correspondence to: Riccardo Polosa, MD, PhD, Università Degli Studi di Catania, Dipartmento di Medicina e Specialistica, 95125 Catania, Italy
Airway inflammation is the major feature of asthma, and represents the major target of the pharmacologic treatment. Currently, individual adjustment of antiasthma medications is mainly based on measurements of symptoms and airflow limitations, but this approach may not be adequate and more specific surrogate markers of airway inflammation should be considered in the routine management of asthma.
The available evidence indicates that adenosine monophosphate (AMP) bronchial provocation seems to offer substantial advantages over other noninvasive markers of airway inflammation because of its exquisite sensitivity in probing changes to airway responsiveness in response to topical glucocorticosteroids,1–3 or to the effects of specific immunotherapy.4
In view of this, the article by Prieto et al (October 2003),5 assessing the utility of the determination of airway responsiveness to inhaled AMP as a predictor for safe dose reduction of inhaled glucocorticosteroids in patients with asthma, is of great value. However, although this work appears to provide enough information to support an important role for AMP provocation in the clinical setting, a number of assertions require judicious scrutiny.
Critical to the whole study is the choice of the cut-off points for AMP sensitivity used for the statistical analysis (400 mg/mL at baseline, and a single doubling concentration decrease in the provocative concentration of AMP causing a 20% fall in FEV1 [PC20] from its baseline value 2 weeks after halving the dose of glucocorticosteroids). This is of particular value in view of the finding that a high level of sensitivity to inhaled AMP was measured in most of the patients who went on to have asthma exacerbations. By arbitrarily setting the cut-off values for PC20 too high, there is the chance of including patients with very mild asthma who are unlikely to have exacerbations. Unfortunately, an optimal cut-off value for PC20 to separate mild from severe asthma has not been established since there are no population-based data, but it would be of interest to repeat the statistical analyses utilizing a different cut-off point (eg, 100 mg/mL).
In addition, a single doubling concentration decrease in PC20 2 weeks after halving the dose of glucocorticosteroids was arbitrarily selected as an end point for establishing the predictive value of AMP responsiveness for failure in glucocorticosteroid reduction. Yet again, given that PC20 is known to return to near-baseline levels on glucocorticosteroid treatment discontinuation,2 it is important to consider that by arbitrarily setting a single doubling concentration decrease in PC20 2 weeks after halving the dose of glucocorticosteroids as a cut-off values, there would be less chance of identifying those patients who are likely to acquire asthma exacerbations. Perhaps repeating the statistics utilizing an alternative cut-off point (eg, three doubling concentrations decrease in PC20) would provide different results. This approach could also provide some explanation to the wide variation in individual clinical responses to glucocorticosteroid dose reduction (as suggested by the broad range in 95% confidence interval) observed in this study.
Finally, as the airway response to a direct bronchoconstrictor agonist is less sensitive to topical glucocorticosteroids,2 it could have been of critical importance to include methacholine provocation in the protocol so as to compare its responses to AMP in relation to the rate of asthma exacerbations provoked by glucocorticosteroid dose reduction.
Despite the emerging view that airway responsiveness to inhaled AMP may have useful clinical applications,5–6 specific recommendations for adenosine challenge testing will require further work. It is important that well-planned and well-conducted large clinical trials must be performed to demonstrate that information gained from this test will lead to improved patient management.
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