Mechanisms underlying corticosteroid resistance in patients with asthma: a review of current knowledge.

IF 2.9 3区医学 Q2 RESPIRATORY SYSTEM Expert Review of Respiratory Medicine Pub Date : 2023-07-01 Epub Date: 2023-09-04 DOI:10.1080/17476348.2023.2255124

Javier Milara, Anselm Morell, Inés Roger, Paula Montero, Julio Cortijo

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Abstract

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.

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哮喘患者皮质类固醇抵抗的潜在机制：当前知识综述。

简介：皮质类固醇是治疗哮喘最具成本效益的抗炎药。尽管它们有效，但一些哮喘患者存在皮质类固醇耐药性或不敏感，反应不佳。皮质类固醇不敏感意味着预后不良，因为在寻找哮喘的替代治疗方案方面存在挑战。涵盖领域：在这篇综述中，我们描述了哮喘表型和内型，以及它们对皮质类固醇的不同反应性。此外，我们还描述了皮质类固醇对糖皮质激素受体（GR）表达的调节及其抗炎作用的作用机制。此外，我们总结了皮质类固醇不敏感哮喘的机制证据，这主要与GR基因表达、结构和转录后修饰的变化有关。最后，讨论了旨在逆转皮质类固醇不敏感的各种药理学策略。专家意见：皮质类固醇不敏感受哮喘表型、内型和严重程度的影响，可作为生物治疗的指征。皮质类固醇不敏感哮喘的分子机制已被用于制定有针对性的治疗策略。然而，缺乏临床试验阻碍了这些治疗方法的临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Respiratory Medicine RESPIRATORY SYSTEM-

CiteScore

6.80

自引率

2.60%

发文量

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