© 2002 American Thoracic Society
ADENOSINE MONOPHOSPHATE CHALLENGE AND MONITORING OF AIRWAY RESPONSE TO ANTIINFLAMMATORY THERAPYTo the Editor :The airway response to adenosine 5'-monophosphate (AMP) in asthma may be used as a specific marker of disease activity with a closer relationship to allergic airway inflammation than histamine or methacholine (1). This is supported by studies where bronchial hyperresponsiveness (BHR) to AMP but not methacholine is better correlated to sputum eosinophilia (2, 3). The findings in the recent study by van den Berge and colleagues (4) demonstrate that AMP may be used as a sensitive marker to monitor the effects of steroid therapy in asthma. To this end, it should be emphasized that the reported greater improvement in BHR to AMP compared with methacholine is likely to be even larger. This is because due to the inclusion criteria (patients were selected on the basis of positive responses to methacholine, not AMP), there were already a number of participants with censored values of PC20 AMP (not methacholine) before corticosteroids (see Table 1 in the article by van den Berge and colleagues [4]). In the case of trials investigating protective pharmacological effects, censored values do not allow enough flexibility, particularly if you are comparing responses with other spasmogens. It would be interesting to recalculate these authors' data by omitting those patients with PC20 AMP > 320 mg/ml at baseline (i.e. before corticosteroids). In accordance with the observations of van den Berge and colleagues (4), the ability of this test in better discriminating changes in BHR with antiinflammatory treatment compared to histamine or methacholine has been already validated with several topical corticosteroids. Conversely, in COPD patients, AMP appears to be as insensitive as methacholine in detecting changes in BHR after treatment with inhaled steroids (5). This diversity is of diagnostic interest, as it may indicate an approach by which AMP may be useful in differentiating asthma from COPD. A limitation of the study by van den Berge and colleagues (4) is that BHR was recorded at an early single time point (after 2 weeks of corticosteroids). Only longitudinal studies can better define a role for AMP in the assessment of antiinflammatory therapy. We have recently examined the time-course of change in sputum cellularity and in BHR to inhaled AMP and methacholine after administration of inhaled budesonide (800 mcg/die) in 10 patients with asthma (6). Budesonide significantly reduced the BHR to AMP as early as by the first week of treatment, whereas changes to methacholine and sputum cellularity could be observed only by the fourth week of treatment. These findings emphasize the superior sensitivity profile of AMP in evaluating antiinflammatory therapy.
University of Catania Catania, Italy REFERENCES
ADENOSINE MONOPHOSPHATE CHALLENGE AND MONITORING OF AIRWAY RESPONSE TO ANTIINFLAMMATORY THERAPYFrom the Authors:We thank Dr. Polosa for his stimulating comments. When reanalyzing our data according to the suggestions of Dr. Polosa (by excluding those patients who were unresponsive to AMP before treatment with corticosteroids) we found similar results (1). Improvement in both PC20 methacholine and in PC20 AMP was associated with reduction in airway inflammation. Independent correlates for improvement in PC20 methacholine were changes in the number of sputum macrophages and eosinophils, whereas changes in the concentration of nitric oxide in exhaled air and the number of sputum eosinophils, lymphocytes, and bronchial epithelial cells were independent correlates for improvement in PC20 AMP. The PC20 AMP was more sensitive to changes in airway inflammation, since the total explained variance for improvement in BHR was much greater for improvement in AMP than for methacholine (34% versus 14%). We agree with Dr. Polosa that the role for AMP in the assessment of antiinflammatory therapy can only be defined in longitudinal studies. In our study, BHR was recorded before and after 2 weeks of treatment with corticosteroids; thus, it was indeed a longitudinal study (2). Nevertheless, it is very interesting to measure the time-course of changes in sputum cellularity and in BHR to AMP and methacholine after administration of corticosteroids over a longer period, and we have read the abstract on asthma patients by Dr. Polosa with great interest (1). Finally, we find Dr. Polosa's suggestion to use the level of improvement in PC20 AMP after treatment with corticosteroids to differentiate between asthma and COPD an interesting one. However, we have previously shown in smokers with COPD that 6 weeks of treatment with 1600 µg budesonide did not improve PC20 methacholine or PC20 AMP. In this respect, PC20 methacholine and PC20 AMP are comparable (3). Thus, we feel that more research is needed to assess whether the PC20 AMP may possibly become a useful tool to differentiate between asthma and COPD.
University Hospital Groningen Groningen, The Netherlands REFERENCES
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