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I read with interest the article on the effects of inhaled fluticasone propionate and oral prednisolone on markers of airway inflammation in asthma recently published inThorax by Meijer et al.1 In particular, it was interesting to read that the magnitude of reduction in airway hyperresponsiveness after fluticasone was more pronounced for adenosine 5′-monophosphate (AMP) than for methacholine. Ketchell et al 2 have recently reported that sensitive prediction of the AMP response to inhaled corticosteroids is already apparent as early as 48 hours. Taken together, these findings further support the use of adenosine challenge as a sensitive and convenient non-invasive test of asthmatic inflammation for potential use in diagnosis, monitoring disease activity, and evaluating treatment efficacy.3
In asthma the ability of this test to discriminate the changes in airway reactivity with anti-inflammatory treatment better than histamine or methacholine has also been validated with inhaled budesonide and the new corticosteroid ciclesonide.4 ,5 In contrast, in patients with chronic obstructive pulmonary disease (COPD) adenosine appears to be as insensitive as methacholine in detecting changes in airway reactivity after treatment with high dose inhaled steroids.6 This diversity is of diagnostic interest as it may indicate an additional way by which adenosine challenge may be useful in differentiating asthma from “true” COPD .
In contrast to the work by Meijer et al,1 Taylor et al 5 have shown that adenosine challenge offers substantial advantages (especially in terms of sensitivity) over that of other non-invasive tests, including induced sputum. The premise for this is that adenosine elicits bronchoconstriction by stimulating the release of bronchoconstrictor mediators from cells/nerves within the airway, and thus may be sensitive to the underlying inflammatory state of the airway. The capacity of adenosine to elicit a much greater bronchoconstrictor response and mediator release from mast cells in atopic subjects than in non-atopic subjects7 ,8 indicates that atopic status is an important determinant of the response.
Current GINA guidelines recommend careful monitoring of asthma symptoms and pulmonary function and recognise the need for “developing non-invasive test(s) of airway inflammation for use in diagnosis, monitoring the disorder's activity, and evaluating treatments”. Despite the emerging view that adenosine bronchoprovocation may be useful for monitoring disease severity, it is important that well planned and well conducted large clinical trials be performed to confirm that information gained from this test will lead to improved patient management.
authors' reply We have read the letter by Dr Polosa with great interest. We support his view that adenosine challenge appears to be a sensitive non-invasive test of asthmatic inflammation with potential use in diagnosis, monitoring disease activity, and evaluating treatment efficacy in asthma. We have previously shown the latter in a head to head comparison of treatment with 250 μg fluticasone and 50 μg salmeterol twice daily for six weeks.1-1 In that study the mean (SD) improvement in PC20 methacholine, expressed in doubling concentrations (DC), was 2.1 (0.5) DC for fluticasone and 1.5 (0.5) DC for salmeterol (fig 1-1). Therapeutic effects on PC20 AMP were greater, with an improvement of 4.5 (0.9) DC for fluticasone and 2.9 (0.9) DC for salmeterol. Usually bronchial hyperresponsiveness is measured during the treatment,1-2-1-4 in our study twice daily.
We have measured treatment efficacy, not only during treatment but also 12 hours after stopping the drugs, which allowed the β agonist bronchodilator effect to be removed (unpublished data). At that time, however, a significant improvement in forced expiratory volume in one second (FEV1) was still seen in both regimens. The improvements in PC20 methacholine were similar to those seen during treatment for both fluticasone and salmeterol. In contrast, the improvement in PC20 AMP with salmeterol had decreased to 2.2 (0.9) DC, while for fluticasone it remained 5.0 (1.1) DC.
Treatment with fluticasone produced a significantly larger bronchoprotective effect to AMP than salmeterol, whereas both drugs had a comparable effect to conventional parameters—that is, PC20 methacholine and FEV1—12 hours after stopping treatment. Given these observations, the results of our study would have led to the conclusion that salmeterol produces effective asthma control after six weeks of treatment, even when given as monotherapy. This would be in accordance with the interantional guidelines1-5 which state that efficient asthma therapy should be related to symptoms and airway obstruction. Yet, a considerable treatment difference was detectable in favour of fluticasone when the effects were tested with AMP.
AMP is more specific in assessing changes in different components of airway wall inflammation than methacholine. Improvement in PC20 AMP might therefore be a better predictor of efficient anti-asthma therapythan changes in the conventionally used parameters, as advised in current guidelines.
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