STEROID-RESISTANT ASTHMA - 03/09/11

Doi : 10.1016/S0889-8561(05)70228-9

Joseph D. Spahn, MD ^a,^b, Ronina Covar, MD ^a

^a Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, Department of Pediatrics, Divisions of Clinical Pharmacology and Allergy and Clinical Immunology, National Jewish Medical and Research Center (JDS, RC)

^b Department of Pediatrics, University of Colorado Health Sciences Center (JDS), Denver, Colorado

Résumé

Asthma is a chronic respiratory disease characterized by reversible airflow limitation and airway hyper-responsiveness to a variety of stimuli. The understanding of the pathogenesis of asthma has evolved from that of a purely bronchospastic disease to one in which airway inflammation plays a central role.^{16 Bousquet J., Chanez P., Lacoste J.Y. , et al. Eosinophilic inflammation in asthma N Engl J Med 1990 ; 323 : 1033-1039 [cross-ref]

Cliquez ici pour aller à la section Références, 55 Robinson D.S., Hamid Q., Ying S. , et al. Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma N Engl J Med 1992 ; 326 : 298-304 [cross-ref]

Cliquez ici pour aller à la section Références} Consequently, there has been a shift from routinely administered bronchodilator therapy to using anti-inflammatory medications earlier in the course of the disease and for patients with less severe asthma. All of the guidelines now recommend an anti-inflammatory agent for all asthmatics except those with mild intermittent asthma.^{24 Expert Panel Report I.I. Guidelines for the Diagnosis and Management of Asthma Bethesda, MD: National Institutes of Health, National Heart, Lung and Blood Institute (1997).
Publication No. xx..

Cliquez ici pour aller à la section Références, 27 International Consensus Report on Diagnosis and Treatment of Asthma 1992 Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute (1992). Publication No. 92–3091.

Cliquez ici pour aller à la section Références} Given that glucocorticoids (GC) have potent anti-inflammatory effects, they constitute the pharmacologic cornerstone of asthma therapy.^{64 Szefler S. Glucocorticoid therapy for asthma: Clinical pharmacology J Allergy Clin Immunol 1991 ; 88 : 147-165 [cross-ref]

Cliquez ici pour aller à la section Références} Inhaled GCs are among the most effective controller therapies for the management of persistent asthma, and systemic GCs are used primarily as rescue therapy for moderate and severe acute manifestations of asthma. Although the majority of asthmatics respond favorably to GC therapy, a subset of individuals do not. These asthmatics are termed steroid resistant (SR).

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Plan

DEFINITION AND CLINICAL CHARACTERISTICS

PATHOGENESIS

Immunologic Features of SR Asthma

Molecular Basis of GC Action

Molecular Basis of SR Asthma

ASSESSMENT OF THE SUSPECTED SR ASTHMATIC

Does the Patient Have Asthma?

Are Other Medical Disorders Contributing to Poor Asthma Control?

Is the Patient Receiving Adequate Asthma Therapy?

Is Poor Compliance a Factor, and is Inhaler Technique Adequate?

Does the Patient Have a Pharmacokinetic Abnormality that Could Contribute to a Poor GC Response?

Have Adequate Environmental Control Measures Been Used?

MANAGEMENT OF THE STEROID-RESISTANT ASTHMATIC

Alternative Therapy

SUMMARY

Address reprint requests to Joseph D. Spahn, MD, National Jewish Medical and Research Center, 1400 Jackson Street (J211), Denver, CO 80206
Supported in part by the National Institutes of Health, Heart, Lung, and Blood Institute, Grants HL-36577 and RR00051.