UC Davis Lung Center, University of California, Davis, CA, United States.
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2021 Feb 26;12:631092. doi: 10.3389/fimmu.2021.631092. eCollection 2021.
Despite recent advances in using biologicals that target Th2 pathways, glucocorticoids form the mainstay of asthma treatment. Asthma morbidity and mortality remain high due to the wide variability of treatment responsiveness and complex clinical phenotypes driven by distinct underlying mechanisms. Emerging evidence suggests that inhalation of the toxic air pollutant, ozone, worsens asthma by impairing glucocorticoid responsiveness. This review discusses the role of oxidative stress in glucocorticoid resistance in asthma. The underlying mechanisms point to a central role of oxidative stress pathways. The primary data source for this review consisted of peer-reviewed publications on the impact of ozone on airway inflammation and glucocorticoid responsiveness indexed in PubMed. Our main search strategy focused on cross-referencing "asthma and glucocorticoid resistance" against "ozone, oxidative stress, alarmins, innate lymphoid, NK and γδ T cells, dendritic cells and alveolar type II epithelial cells, glucocorticoid receptor and transcription factors". Recent work was placed in the context from articles in the last 10 years and older seminal research papers and comprehensive reviews. We excluded papers that did not focus on respiratory injury in the setting of oxidative stress. The pathways discussed here have however wide clinical implications to pathologies associated with inflammation and oxidative stress and in which glucocorticoid treatment is essential.
尽管近年来在使用针对 Th2 途径的生物制剂方面取得了进展，但糖皮质激素仍是哮喘治疗的主要药物。由于治疗反应的广泛可变性和由不同潜在机制驱动的复杂临床表型，哮喘的发病率和死亡率仍然很高。新出现的证据表明，吸入有毒空气污染物臭氧会通过损害糖皮质激素反应性而使哮喘恶化。这篇综述讨论了氧化应激在哮喘中糖皮质激素抵抗中的作用。潜在的机制表明氧化应激途径起着核心作用。这篇综述的主要数据来源是在 PubMed 上索引的关于臭氧对气道炎症和糖皮质激素反应性影响的同行评审出版物。我们的主要搜索策略侧重于将“哮喘和糖皮质激素抵抗”与“臭氧、氧化应激、警报素、先天淋巴细胞、NK 和 γδ T 细胞、树突状细胞和肺泡 II 型上皮细胞、糖皮质激素受体和转录因子”交叉引用。最近的工作是根据过去 10 年的文章和较旧的开创性研究论文和综合评论来进行的。我们排除了那些没有关注氧化应激背景下呼吸道损伤的论文。然而，这里讨论的途径与炎症和氧化应激相关的病理学具有广泛的临床意义，而糖皮质激素治疗在这些病理学中是必不可少的。
