Introduction: For decades glucocorticoids have been considered as the gold standard for the treatment of asthma. We present a case report of typical glucocorticoid-resistant asthma and current consensus in definitions of "severe refractory", "difficult" and "glucocorticoid-resistant" asthma.
Methods: Full-text papers and abstracts were identified on the basis of a comprehensive literature search primarily in MEDLINE (1966 to June 2012) but also in the Cochrane Central Register of Controlled Trials database.
Results: Glucocorticoid-resistant asthmatics are a small subset of patients who pose noteworthy diagnostic challenges while contributing disproportionately to health care costs. Recognition of various asthma phenotypes has aided in characterizing groups with severe asthma and given a better understanding of its pathophysiological process. The molecular mechanism of glucocorticoid action is complicated and several pathways have been identified to explain drug resistance, which in turn is crucial for drug development. Tobacco smoking appears to be the single most important contributor of glucocorticoid resistance. We present the emerging and promising concepts in the management of glucocorticoid-resistant asthma, which mainly include drugs targeting specific molecules, receptors, inflammatory cells or immune processes.
Conclusion: The challenges in making a diagnosis of glucocorticoid-resistant asthma may contribute to underestimating its prevalence and impact on patient care. Considerable progress has been made in identifying distinct phenotypes and mechanisms of glucocorticoid resistance; therefore the future of new drug development in management of asthma is promising.
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http://dx.doi.org/10.3109/02770903.2013.831870 | DOI Listing |
Front Biosci (Landmark Ed)
January 2024
Department of Respiratory Medicine, The First Hospital of Jilin University, 130021 Changchun, Jilin, China.
Understanding the pathogenesis of different phenotypes of asthma, including glucocorticoid-dependent and glucocorticoid-resistant asthma, is crucial for the development of effective treatments. Autophagy, a fundamental cellular process involved in cell homeostasis, has been implicated in asthma, although the exact mechanisms remain unclear. Recent studies have identified autophagy activation in eosinophilic, neutrophilic, and paucigranulocytic asthma, providing novel insights into the disease.
View Article and Find Full Text PDFMol Pharmacol
December 2023
Departments of Physiology and Pharmacology (A.B., K.K., S.G., A.T., P.C., A.N.-B., M.M.M., A.M., R.N.) and Medicine (C.K., R.L.), Lung Health Research Group, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Alberta, Canada
Glucocorticoids act via the glucocorticoid receptor (GR; NR3C1) to downregulate inflammatory gene expression and are effective treatments for mild to moderate asthma. However, in severe asthma and virus-induced exacerbations, glucocorticoid therapies are less efficacious, possibly due to reduced repressive ability and/or the increased expression of proinflammatory genes. In human A549 epithelial and primary human bronchial epithelial cells, toll-like receptor (TLR)-2 mRNA and protein were -additively induced by interleukin-1 (IL-1) plus dexamethasone (IL-1+Dex), interferon- (IFN-) plus dexamethasone (IFN-+Dex), and IL-1 plus IFN- plus dexamethasone (IL-1+IFN-+Dex).
View Article and Find Full Text PDFRespir Res
March 2023
Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, 610041, China.
Toxins (Basel)
April 2022
Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA.
Glucocorticoid-resistant asthma, which predominates with neutrophils instead of eosinophils, is an increasing health concern. One potential source for the induction of neutrophil-predominant asthma is aerosolized lipopolysaccharide (LPS). Cyanobacteria have recently caused significant tidal blooms, and aerosolized cyanobacterial LPS has been detected near the cyanobacterial overgrowth.
View Article and Find Full Text PDFMar Drugs
October 2021
Department of Medicine I-Pulmonary Rehabilitation Clinic, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania.
One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets.
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