Steroid-unresponsive asthma

Abstract

Although most patients with chronic asthma respond to corticosteroid therapy, a small subset of asthmatics are unresponsive to corticosteroids and demonstrate persistent airway obstruction and inflammation despite treatment with high doses of systemic glucocorticoids. There are at least two types of steroid-resistant asthma. Type I steroid-resistant (SR) asthma is cytokine induced and is associated with increased expression of glucocorticoid receptor beta, a less active glucocorticoid receptor isoform. Type II SR asthma is due to low numbers of glucocorticoid receptors. An important distinction between these two types of SR asthma is that the glucocorticoid receptor defect in Type I, but not Type II, SR asthma is reversible in culture and is sustained by incubation with combination interleukin (IL)-2 and IL-4. The treatment of these patients requires a systematic approach to rule out underlying conditions that lead to steroid resistance or treatment failure as well as the use of alternative strategies to inhibit airway inflammation.