Beyond pathogens: a narrative review of the immunological nexus of damage-associated molecular patterns and inflammasome activation in sterile AECOPD

The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has traditionally been attributed to pathogen-associated molecular patterns (PAMPs); however, emerging evidence highlights the critical role of damage-associated molecular patterns (DAMPs) in driving sterile inflammation during these episodes. The NLR Family Pyrin Domain Containing 3(NLRP3) inflammasome, a pivotal component of the innate immune system, mediates inflammatory responses that contribute significantly to the pathogenesis of AECOPD. Building upon the integration of current research on the molecular mechanisms of DAMP-NLRP3 inflammasome interaction, this review further emphasizes its immunological significance in sterile AECOPD. Furthermore, we explore how viral infections, such as the influenza virus, potentiate inflammasome activation and exacerbate inflammatory cascades, thereby influencing clinical outcomes. By integrating recent experimental and clinical findings, this article aims to provide a comprehensive understanding of the immune regulatory mechanisms involved in AECOPD beyond microbial triggers. Such insights are essential to advancing precision therapeutic strategies targeting inflammasome pathways and improving patient management.