Therapeutic potential of targeting novel signaling pathways in regulating chronic inflammation in obstructive lung disorders

Chronic obstructive pulmonary disease (COPD) and asthma are two major obstructive lung disorders characterized by persistent airway inflammation that leads to progressive lung function decline. Although both chronic in nature, the inflammatory profiles that characterize these diseases differ significantly: COPD is predominantly driven by neutrophilic inflammation, whereas allergic asthma, a major subtype of asthma disease, is traditionally associated with eosinophilic and T helper 2 (Th2)-mediated responses. This review explores first the mechanisms underlying chronic inflammation in COPD and asthma, emphasizing thereafter the impact of bacterial and viral infections in exacerbating inflammatory responses and accelerating lung damage. Current therapeutic approaches, including the use of corticosteroids, bronchodilators, and biologics, are evaluated, highlighting their mechanisms of actions and limitations. Finally, the review focuses on novel therapeutic targets that have emerged from recent advances in (airway) inflammation research. The roles of key signaling pathways such as those involving Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), C-X-C motif chemokine receptor 2 (CXCR2), toll-like receptors (TLRs), tumor necrosis factor (TNF) signaling, P2X purinoceptor 4 (P2X4 receptor), and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in sustaining chronic inflammation are discussed. Understanding these pathways offers insights into the potential for development of more targeted and effective treatments. By offering a comprehensive overview of both established and (potential) novel approaches, this review aims to promote the identification and development of therapeutic strategies that could revolutionize the options for effective treatment of chronic inflammation in obstructive lung disorders.