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

Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients

“…In contrast, GC-R patients may suffer serious side effects because of escalation of drug dose caused by hyporesponsiveness. GC resistance has been defined as the lack of a response to a prolonged course of high-dose (0.5-1.0 mg͞kg per day) oral GC (20,21). Because modern asthma therapy is largely centered on inhaled GC, a definition referring to GC-R asthma taking into account the inhalation route in the use of these drugs has been proposed (26).…”

“…All patients were categorized as either GC-S or GC-R based on standard clinical and laboratory parameters (19)(20)(21). The inclusion criteria for the GC-S patients enrolled included documentation of good clinical response to conventional doses of inhaled GC therapy (i.e., Յ1,000-g inhalation of GC in 24 h) as measured by one or more of the following parameters: improvement in asthma symptoms, improved lung function tests (i.e., FEV1 and peak expiratory flow), reduced requirements for ␤-agonist rescue therapy, or reduced frequencies of pulmonary exacerbations when taking inhaled GC in recommended therapeutic doses.…”

“…In addition, the GC-R patients failed to demonstrate clinical or pulmonary function improvement on a 7-to 14-day course of oral GC (40-60 mg per day of prednisolon), a criterion widely accepted when defining GC resistance (20,21).…”

Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion

“…These patients generally require prolonged systemic treatment, their asthma is less stable and more difficult to control and they are subject to higher morbidity and mortality (3)(4)(5)(6)). The precise cause or causes of SR asthma are unknown, but several mechanisms have been proposed to account for it (reviewed in (7-10)), including genetic susceptibility, defects in glucocorticoid receptor (GR) binding, increased expression of the functionally inactive GR-, activation of transcription factors such as AP-1 (activator protein 1) or decreased synthesis of immunoregulatory cytokines like IL-10.…”

Nuclear bioavailability of the glucocorticoid receptor in a pediatric asthma cohort with variable corticosteroid responsiveness

“…While some GC-insensitive patients do respond to higher doses than normally prescribed, the administration of these higher doses for prolonged periods can have marked adverse effects. Moreover, poor clinical responses have been observed even among asthmatics receiving high doses of systemic corticosteroids (6). The economic burden of asthma on healthcare systems is significant, particularly due to the mismanagement of severe asthmatics (3,7).…”