Divya Reddy1, Frederic F Little. 1. Department of Pulmonary, Allergy, Sleep and Critical Care Medicine, Pulmonary Center, Boston University School of Medicine , Boston, MA , USA.
Abstract
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.
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.
Authors: E Sherwood Brown; Nasreen Sayed; Erin Van Enkevort; Alexandra Kulikova; Alyson Nakamura; David A Khan; Elena I Ivleva; Prabha Sunderajan; Bruce G Bender; Traci Holmes Journal: J Allergy Clin Immunol Pract Date: 2018-03-01
Authors: Dimitri Tränkner; Nadeau Hahne; Ken Sugino; Mark A Hoon; Charles Zuker Journal: Proc Natl Acad Sci U S A Date: 2014-07-21 Impact factor: 11.205
Authors: X Chen; Y Gan; W Li; J Su; Y Zhang; Y Huang; A I Roberts; Y Han; J Li; Y Wang; Y Shi Journal: Cell Death Dis Date: 2014-01-23 Impact factor: 8.469
Authors: Thomas Southworth; Jonathan Plumb; Vandana Gupta; James Pearson; Isabel Ramis; Martin D Lehner; Montserrat Miralpeix; Dave Singh Journal: Respir Res Date: 2016-10-04
Authors: Sorif Uddin; Augustin Amour; David J Lewis; Chris D Edwards; Matthew G Williamson; Simon Hall; Lisa A Lione; Edith M Hessel Journal: BMC Immunol Date: 2021-12-17 Impact factor: 3.615
Authors: Leah R Reznikov; David K Meyerholz; Mahmoud Abou Alaiwa; Shin-Ping Kuan; Yan-Shin J Liao; Nicholas L Bormann; Thomas B Bair; Margaret Price; David A Stoltz; Michael J Welsh Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-04-05 Impact factor: 5.464