Steroid-resistant asthma: evaluation and management.
OBJECTIVE
Reading this article will reinforce the reader's knowledge of the definition, pathophysiology, differential diagnosis, and treatment of the steroid-resistant asthmatic patient.


METHODS
Prospective and retrospective data from the authors' experience were evaluated. In addition, a Medline database was searched from 1981, using the key words "asthma," "glucocorticoids," and "glucocorticoid resistance" with the restrictions of English language and human subjects. Relevant articles referenced in retrieved sources and current texts on severe asthma were also utilized.


METHODS
Data source abstracts, pertinent articles, and book chapters meeting the objectives were critically reviewed.


RESULTS
Although rare, individuals with steroid-resistant asthma are often the most difficult-to-manage asthmatic patients in that they have severe disease yet fail to respond to glucocorticoids. To make the diagnosis of steroid-resistant asthma, the patient must fail to respond to a 7 to 14-day course of daily prednisone as measured by less than a 15% improvement in morning prebronchodilator FEV1 following the glucocorticoid course. Ongoing inflammation is thought to play a major role in the pathogenesis of steroid-resistant asthma, and recent studies have demonstrated diminished glucocorticoid receptor to glucocorticoid, or diminished glucocorticoid receptor to DNA binding as possible mechanisms for diminished glucocorticoid responsiveness. Alternative asthma therapies such as methotrexate, cyclosporine, and intravenous gammaglobulin are often used in this group of asthmatic patients.


CONCLUSIONS
The patient with steroid-resistant asthma presents several challenges. These individuals often display many of the sequelae of long-term systemic glucocorticoid use while achieving little therapeutic benefit. Prior to making the diagnosis of steroid-resistant asthma, diseases that can contribute to poor control of asthma must be ruled out, and noncompliance issues addressed. Alternative asthma therapies are often used; however, they also carry the potential for adverse effects, and have not been thoroughly studied in this population of asthmatic patients.
Nimmagadda
S R
SR
Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, University of Colorado Health Sciences Center, Denver, USA.
Spahn
J D
JD
Leung
D Y
DY
Szefler
S J
SJ
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D003937:Diagnosis, Differential; D004351:Drug Resistance; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans
D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids