From Inflammation to Precision Medicine: Mechanistic Insights into Asthma, COPD, and IPF

Abstract

Asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are major non-communicable respiratory diseases (NCD-RDs) with high morbidity and mortality. Despite distinct clinical features, they share overlapping mechanisms including oxidative stress, epithelial injury, and immune dysregulation. Asthma is mainly driven by type 2 inflammation, with IL-4, IL-5, and IL-13 inducing eosinophilia, IgE production, mucus hypersecretion, and airway remodeling. Biologics targeting IgE, IL-5, and IL-4Rα have transformed treatment, and agents directed against TSLP and IL-33 further extend the range of targeted interventions. In contrast, COPD involves chronic inflammation with macrophages, neutrophils, and CD8+ T cells, persisting after smoking cessation. Advances include biologics such as dupilumab and benralizumab in eosinophilic COPD, and novel inhaled therapies such as ensifentrine, the first dual PDE3/4 inhibitor delivered via inhalation. IPF, on the other hand, arises from defective epithelial repair and fibroblast activation, causing progressive fibrosis. Approved antifibrotics (nintedanib, pirfenidone) slow lung function decline, while new strategies target TGF-β, CTGF, and fibroblast-directed pathways. Across these diseases, biomarkers and the treatable traits framework are reshaping precision care. Personalized approaches integrating biomarkers, omics, and targeted therapies represent the most promising path for improved outcomes.