The development of effective treatments in this patient population is impeded by the lack of clarity regarding potential underlying mechanisms, as well as the variety of heterogeneous endotypes of severe, steroid-resistant asthma. Although the condition is often linked with non-eosinophilic asthma endotypes 4,5 such as neutrophilic asthma, other findings suggest the involvement of persistent eosinophilic inflammation in severe disease. 6 “This heterogeneity of disease and likely involvement of different underlying immunological, inflammatory, and molecular mechanisms in different subtypes of severe, steroid-resistant asthma has hampered the development of effective therapies,” Dr Hansbro and colleagues wrote in a review recently published in Immunological Reviews. 7
Glucocorticoid (GC) responsiveness represents a continuous spectrum, with GC-resistant individuals falling at one end of a unimodal distribution. Patients with severe asthma who are poorly responsive to high doses of GCs and are without confounding factors ( table 1 ) have been termed GC-resistant [ 1 ]. A larger subset of patients with asthma that is poorly-controlled despite optimal treatment or who experience worsening of asthma control during GC withdrawal have severe asthma and are considered relatively GC-insensitive [ 1 ]. High doses of GCs usually indicate a daily dose of 1000 microg or more of inhaled fluticasone propionate or 2000 microg or more of triamcinolone, the equivalent ( table 2 ).