Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrent'ev Ave 8, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2023 Nov 7;24(22):16042. doi: 10.3390/ijms242216042.
Bronchial asthma is a heterogeneous disease characterized by persistent respiratory system inflammation, airway hyperreactivity, and airflow obstruction. Airway remodeling, defined as changes in airway wall structure such as extensive epithelial damage, airway smooth muscle hypertrophy, collagen deposition, and subepithelial fibrosis, is a key feature of asthma. Lung fibrosis is a common occurrence in the pathogenesis of fatal and long-term asthma, and it is associated with disease severity and resistance to therapy. It can thus be regarded as an irreversible consequence of asthma-induced airway inflammation and remodeling. Asthma heterogeneity presents several diagnostic challenges, particularly in distinguishing between chronic asthma and other pulmonary diseases characterized by disruption of normal lung architecture and functions, such as chronic obstructive pulmonary disease. The search for instruments that can predict the development of irreversible structural changes in the lungs, such as chronic components of airway remodeling and fibrosis, is particularly difficult. To overcome these challenges, significant efforts are being directed toward the discovery and investigation of molecular characteristics and biomarkers capable of distinguishing between different types of asthma as well as between asthma and other pulmonary disorders with similar structural characteristics. The main features of bronchial asthma etiology, pathogenesis, and morphological characteristics as well as asthma-associated airway remodeling and lung fibrosis as successive stages of one process will be discussed in this review. The most common murine models and biomarkers of asthma progression and post-asthmatic fibrosis will also be covered. The molecular mechanisms and key cellular players of the asthmatic process described and systematized in this review are intended to help in the search for new molecular markers and promising therapeutic targets for asthma prediction and therapy.
支气管哮喘是一种异质性疾病，其特征为持续的呼吸系统炎症、气道高反应性和气流阻塞。气道重塑是哮喘的一个关键特征，定义为气道壁结构的变化，如广泛的上皮损伤、气道平滑肌肥大、胶原沉积和上皮下纤维化。肺纤维化是致命性和长期哮喘发病机制中的常见现象，与疾病严重程度和治疗抵抗有关。因此，它可以被视为哮喘引起的气道炎症和重塑的不可逆转后果。哮喘的异质性带来了几个诊断挑战，特别是在区分慢性哮喘和其他以正常肺结构和功能破坏为特征的肺部疾病（如慢性阻塞性肺疾病）方面。寻找能够预测肺部不可逆结构变化（如气道重塑和纤维化的慢性成分）发展的工具尤其具有挑战性。为了克服这些挑战，人们正在努力寻找能够区分不同类型哮喘以及具有相似结构特征的其他肺部疾病的分子特征和生物标志物，包括哮喘和其他肺部疾病。本文将讨论支气管哮喘的病因、发病机制和形态学特征，以及哮喘相关的气道重塑和肺纤维化作为一个连续过程的各个阶段。本文还将介绍哮喘进展和哮喘后肺纤维化的常见小鼠模型和生物标志物。本文中描述和系统化的哮喘过程的分子机制和关键细胞参与者旨在帮助寻找新的分子标志物和有前途的治疗靶点，以用于哮喘的预测和治疗。
