Glucocorticoid Insensitive Asthma

Part of the Allergy Frontiers book series (ALLERGY, volume 5)

It has been understood for some time that, although the majority of patients with asthma respond well to corticosteroid (CS) therapy, a small subgroup exists in whom CSs either have no effect on asthma or its components, or in whom the dose required to cause an improvement, greatly exceeds the usual therapeutic range. As CSs are widely recognized as the most effective therapy currently available for asthma, a poor response to CSs may contribute to the development of severe asthma. However, GC insensitive asthma is not synonymous with difficult-to-treat asthma, as it has been recognized that child and adult asthmatics with a wide range of severity may exhibit a lower than expected response [1, 2]. Yet, it is the group of patients with difficult-to-treat asthma, who are also refractory to treatment with CSs, who likely contribute to nearly 50% of the economic burden of the disease [3].

For many years, CS insensitivity was described as being related to a direct abnormality in the glucocorticoid (GC) pathway (i.e., receptor, translocation, transcription factor binding). However, it is now understood that GC insensitive asthma is likely to be much more complex than originally described, with numerous other factors also contributing to an absent or diminished CS response, which may have little to do with molecular pathways. After defining GC insensitivity, this review will describe the current understanding of four potential reasons for GC insensitivity. These include: (1) abnormal activation of the GC receptor and its nuclear inhibitory effects, (2) the presence of a “different” inflammatory process that may not respond to CS therapy, (3) the lack of any inflammatory process and (4) the presence of an inflammatory process in a region of the lung, poorly accessible to inhaled therapy. A fifth reason for GC insensitivity also exists, namely, non-adherence/compliance with CS medications. However, that reason for GC insensitivity will not be discussed further in this chapter. This chapter will conclude with a section on approaches to treatment of GC insensitive asthma (Table 1).


Severe Asthma Allergy Clin Immunol Respir Crit Eosinophilic Inflammation Distal Lung 
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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.University of PittsburghPittsburghUSA

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