Javier Milara, Anselm Morell, Inés Roger, Paula Montero, Julio Cortijo
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Mechanisms underlying corticosteroid resistance in patients with asthma: a review of current knowledge.
Introduction: Corticosteroids are the most cost-effective anti-inflammatory drugs available for the treatment of asthma. Despite their effectiveness, several asthmatic patients have corticosteroid resistance or insensitivity and exhibit a poor response. Corticosteroid insensitivity implies a poor prognosis due to challenges in finding alternative therapeutic options for asthma.
Areas covered: In this review, we describe asthma phenotypes and endotypes, as well as their differential responsiveness to corticosteroids. In addition, we describe the mechanism of action of corticosteroids underlying their regulation of the expression of glucocorticoid receptors (GRs) and their anti-inflammatory effects. Furthermore, we summarize the mechanistic evidence underlying corticosteroid-insensitive asthma, which is mainly related to changes in GR gene expression, structure, and post-transcriptional modifications. Finally, various pharmacological strategies designed to reverse corticosteroid insensitivity are discussed.
Expert opinion: Corticosteroid insensitivity is influenced by the asthma phenotype, endotype, and severity, and serves as an indication for biological therapy. The molecular mechanisms underlying corticosteroid-insensitive asthma have been used to develop targeted therapeutic strategies. However, the lack of clinical trials prevents the clinical application of these treatments.
期刊介绍:
Coverage will include the following key areas:
- Prospects for new and emerging therapeutics
- Epidemiology of disease
- Preventive strategies
- All aspects of COPD, from patient self-management to systemic effects of the disease and comorbidities
- Improved diagnostic methods, including imaging techniques, biomarkers and physiological tests.
- Advances in the treatment of respiratory infections and drug resistance issues
- Occupational and environmental factors
- Progress in smoking intervention and cessation methods
- Disease and treatment issues for defined populations, such as children and the elderly
- Respiratory intensive and critical care
- Updates on the status and advances of specific disease areas, including asthma, HIV/AIDS-related disease, cystic fibrosis, COPD and sleep-disordered breathing morbidity