Asthma Pathogenesis: Clinical Expression, Molecular Mechanisms, and Risk Factors

Abstract: With variable airflow obstruction, bronchial hyperresponsiveness, and persistent inflammation, asthma is a chronic respiratory disorder characterized by its complex pathogenesis. This review further explores the complex pathogenesis of asthma by examining various clinical phenotypes, molecular mechanisms, and multifactorial risk factors. Asthma shows phenotypic heterogeneity clinically, often classified along immune profiles and biomarkers with eosinophilic and non-eosinophilic endotypes. At the molecular level, asthma is manifested as dysregulated immune responses, primarily Th2-mediated and, in some instances, Th17-mediated inflammation using cytokines IL-4, IL-5, IL-13, and IL-17. Furthermore, the airway remodelling layer, consisting of epithelial-mesenchymal transition, goblet cell hyperplasia, and subepithelial fibrosis, facilitates this progression. Genetic susceptibility, epigenetic changes, and alterations in gut microbiota contribute to immune dysregulation, while environmental triggers like allergens, pollutants, and infections worsen the disease. The genetic predisposition, environmental influences, and immune regulation are shown to be inextricably intertwined, emphasizing the need to use a phenotype- and endotype- based approach in the hope of providing better personalized care for asthma and saving the world from its burden.