© 2004 American Thoracic Society
"Refractory" Eosinophilic Airway Inflammation in Severe AsthmaTo the Editor:The recent study by ten Brinke and colleagues (1) should make us pause to consider the direction in which research into the mechanisms of refractory asthma is heading. Their data demonstrate that use of intramuscular triamcinolone, in patients with refractory asthma, leads to a reduction in sputum eosinophils and rescue medication score and an increase in FEV1. The authors suggest that a possible explanation for their findings is that triamcinolone may reach areas of the lung, as well as the bone marrow, that are inaccessible to inhaled corticosteroids. However, this does not explain why intramuscular treatment should be superior to oral, unless there is a problem with gastrointestinal absorption. The authors also acknowledge, albeit without much conviction, that poor adherence to maintenance corticosteroids might play a role. Many believe that poor treatment adherence is an important cause of refractory asthma. However, there are surprisingly few published data to support this view, and compared with the advances made in understanding the cellular and molecular basis of refractory asthma, the assessment of adherence remains a neglected area. All the currently available methods for assessing adherence to inhaled therapy, including electronic monitors, have their limitations (2), which may explain why only one of several recent descriptive studies of patients with refractory asthma has attempted to provide objective data on adherence to inhaled therapy (3). Several groups have measured serum prednisolone and cortisol to assess adherence to oral prednisolone (1, 3–6), although this method also has drawbacks. Detectable prednisolone only reflects short-term adherence, whereas measurement of cortisol is an indirect method, which assumes that demonstration of adrenal suppression reflects corticosteroid use. However, a single cortisol measurement only reliably reflects adrenal suppression when the level is low (< 100 nM) (4). Levels greater than 100 nM are harder to interpret. These difficulties most likely explain the paucity of published data. One of the advantages of administering intramuscular triamcinolone is that adherence is assured. In their study, ten Brinke and colleagues (1) have demonstrated that significant improvements are possible, even in adults with refractory, eosinophilic asthma, providing patients receive an adequate corticosteroid dose. This highlights the need to establish what proportion of those with refractory asthma really are receiving the corticosteroid dose they are prescribed and to develop ways of improving adherence, where appropriate. Our own practice is to diagnose steroid-insensitive asthma only after a failed trial of intramuscular triamcinolone, and we suggest that this be incorporated into the definition of this problem.
Royal Brompton Hospital London, United Kingdom FOOTNOTES Conflict of Interest Statement: A.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter; D.N.R.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter. REFERENCES
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