Difficult-to-control asthma: Clinical characteristics of steroid-insensitive asthma

Background: Although widely used, little is known regarding the patterns of response that subjects with severe asthma exhibit to oral glucocorticoid (GC) therapy. Methods: We retrospectively reviewed the charts of 164 consecutive adolescents admitted to the National Jewish Medical and Research Center for difficult-to-control asthma, Data collected included medical history, pulmonary function measures by plethysmography, methacholine challenge results, AM cortisol levels, serum IgE, total eosinophil counts (TEC), serum eosinophil cationic protein (ECP), soluble IL-2 receptor (sIL-2R), and spirometry, Results: Eighty-seven patients (53%) required a GC burst during the hospitalization secondary to poor asthma control. Those requiring a GC burst had a significantly longer history of asthma, a greater degree of bronchial hyperresponsiveness, and lower pulmonary function. Twenty-one patients (24%) failed to respond with a greater than 15% improvement in their AM prebronchodilator FEV, after the GC burst and were termed steroid insensitive (SI). Although those with SI asthma had a similar duration of asthma, they required oral GC therapy at a younger age, required a larger maintenance oral GC dose on admission, and were more likely to be African-American, compared with those with steroid-sensitive asthma. Furthermore, two distinct spirometry patterns were noted among the SI asthmatic subjects: "chaotic" and "non-chaotic." Patients with the chaotic pattern were characterized by a significant degree of variability (greater than 30%) in daily pulmonary function, whereas those with nonchaotic, SI asthma were characterized by less than 15% variability in daily lung function. Those with nonchaotic SI were diagnosed with asthma and treated with oral GCs at a later age. Conclusions: This retrospective study suggests that SI asthma is quite common (25%) among adolescents with severe asthma evaluated at a national referral center, In addition, two distinct patterns of SI asthma have been identified that mag constitute different pathophysiologic processes. Finally, the overrepresentation of African-Americans in the SI group supports the need for further epidemiologic studies investigating the prevalence of SI asthma and the impact early asthma intervention may have on this severe form of asthma.