Pathogenetic aspects of steroid-resistant severe bronchial asthma

Purpose of the review. The purpose of this review was to summarize the available relevant data on pathogenetic mechanisms in the formation of steroid resistance in severe bronchial asthma. Material and methods. The analysis of domestic sources on the CyberLeninka and e-Library scientific electronic libraries, and the search for published foreign full-text articles, reviews, systematic reviews, meta-analysis data and randomized clinical trials in PubMed/Medline were conducted to summarize relevant material on the pathophysiology of steroid-resistant asthma. In addition, a reverse search was conducted for links to relevant studies. Publications from 2020 to 2024 were considered for consideration. The analysis included full-fledged articles and the results of clinical trials containing information on key cytokines of neutrophilic asthma: IL-33, IL-17, TNF, IFNγ. A search for the term “steroid-resistant asthma” for the specified period (2020–2024) initially revealed a list of 93 articles. 62 articles presented in the form of abstracts or not corresponding to the target topic were excluded from the general list. A total of 31 publications from an electronic search in the PubMed database and 17 articles additionally found using a manual search were included in the analysis. Results. Bronchial asthma (BA) is an extremely heterogeneous respiratory disease characterized by airway obstruction, bronchial hyperreactivity, and airway inflammation. About 3-10% of asthma patients suffer from uncontrolled severe asthma. The main difference between patients with severe form of the disease and patients with mild and moderate asthma is resistance to basic therapy drugs – glucocorticosteroids. Severe bronchial asthma is heterogeneous and includes different immunophenotypes: Th2-high (eosinophilic inflammation), Th2-low and Th17-high (non-eosinophilic inflammation accompanied by neutrophilic inflammation of the respiratory tract), mixed Th1/Th17-mediated inflammation. Conclusion. The paper provides information for determining common points of interaction between different immune mediators and related mechanisms related to respiratory tract inflammation and the immunobiology of steroid-resistant asthma.