Corticosteroid Resistant Asthma

CR asthma is associated with disease chronicity, a positive family history of asthma and in vitro and in vivo defects in mononuclear cell function. The HPA axis in CR asthmatics is suppressed normally by dexamethasone and the pharmacokinetic profile of an oral dose of prednisolone is similar to that found in CS subjects. In addition, competitive binding studies have shown that the ligand binding and nuclear translocation functions of the GR are similar in the two groups. Studies using gel retardation assay have indicated a defect in DNA binding in CR subjects. Chemical mutational analysis of the GR has shown that is not due to a defect in its structure at the cDNA level. Scatchard analysis of the GR/DNA and GR/ligand interactions suggests that there may be transcriptional interference of the GR with other transcriptionally active molecules leading to defective gene transcription.