© 2004 American Thoracic Society
"Refractory" Eosinophilic Airway Inflammation in Severe AsthmaFrom the Authors:We thank Drs. Payne and Bush for their critical comments on our article (1). We do agree that a diagnosis of "steroid-insensitive asthma" should be made with caution, in particular because of the possibility of noncompliance with therapy, which is probably an underestimated problem in this category of patients. We also sympathize in principle with their proposition to incorporate a failed trial with intramuscular triamcinolone into the diagnosis of steroid-insensitive asthma, although it must be kept in mind that in case of an unforeseen steroid-induced complication such as diabetes, hypertension, or psychiatric disturbances, there is no possibility to discontinue the treatment. In our clinic, we rather prefer a trial with intravenous corticosteroids in a hospital setting, where allergen avoidance can be guaranteed at the same time. Although difficult to prove, we do not think that noncompliance was the major cause of the lack of sufficient response to therapy in our patients. These patients were intensively managed by a chest physician, repeatedly informed about the importance of regular treatment, and were highly motivated to participate in the study. In six out of seven patients on regular oral corticosteroids, cortisol levels were adequately suppressed (< 100 nM), while sputum eosinophil percentages were still elevated. This means either that the patients had poor perception of dyspnea and were relatively undertreated, or that the patients (and their doctors) accepted a certain level of symptoms to avoid the side effects of higher doses of systemic corticosteroids. In our view, such patients represent a specific subgroup of patients with severe asthma who cannot be controlled with inhaled medication or low dose oral corticosteroids alone rather than patients who are noncompliant with prescribed therapy. The observation that patients on regular oral corticosteroids further improved after intramuscular triamcinolone is probably due to the extremely high doses of triamcinolone (120 mg) that were administered in this study. Obviously, such high doses of regular systemic corticosteroids are not recommended in clinical practice! On the basis of the results of our study, we are convinced that a subgroup of patients with severe asthma needs potent systemic antiinflammatory therapy for optimal control of their disease, which should preferably be associated with less serious side effects than high dose oral or intramuscular corticosteroids.
a Medisch Centrum Leeuwarden Leeuwarden, the Netherlands FOOTNOTES Conflict of Interest Statement: A.t.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; A.H.Z. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; P.J.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; K.F.R. has been consulting, participated in Advisory Board meetings and received lecture fees from AltanaPharma, Novartis, AstraZeneca, GlaxoSmithKline, Pfizer, Boehringer, and Merck Sharp & Dohme; E.H.B. has participated in Advisory Board meetings of Merck Sharp & Dohme from 2001 until 2004. The Department of Pulmonology at Leiden University Medical Center has received grants from AltanaPharma, Novartis, Bayer, AstraZeneca, Pfizer, Merck Sharp & Dohme, Exhale Therapeutics, and GlaxoSmithKline in the years 2001 until 2004. REFERENCES
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