Key points are not available for this paper at this time.
The core pathology of asthma involves not only inflammation amplification but also a systemic failure of inflammation resolution programs. This review first summarizes the Specialized Pro-resolving Mediators (SPM) family, efferocytosis, and their molecular basis in maintaining respiratory system homeostasis, emphasizing the positive feedback loop between lipid mediator class switching and macrophage reprogramming. Subsequently, it delineates the structural and functional characteristics of asthmatic airway remodeling and compiles evidence from human samples, animal models, and in vitro experiments regarding impaired SPM generation, attenuated receptor signaling, and reduced efferocytosis efficiency. This reveals a cascade mechanism of “SPM deficiency-–efferocytosis impairment-–secondary necrosis-–structural damage.” Furthermore, the review discusses the links between severe/refractory phenotypes, early-onset airway remodeling, and high eosinophilic/mixed granulocytic inflammation with resolution defects from the perspective of clinical phenotypes and biomarkers. It proposes the potential of composite indicators such as SPM profiles, Damage-Associated Molecular Patterns (DAMPs) levels, and phagocytic indices in stratified management and efficacy prediction. In the therapeutic and translational section, the review systematically compares the effects of exogenous SPMs, SPM generation/receptor modulators, efferocytosis-enhancing strategies, and traditional Inhaled Corticosteroids (ICS) and biologics on resolution pathways. It proposes an approach where “pro-resolving pharmacology” synergizes with existing anti-inflammatory therapies. Finally, the review addresses the limitations of current evidence regarding sample size, detection methods, and model constraints, calling for the inclusion of standardized resolution indicators and imaging/histological endpoints in prospective cohorts and clinical trials to promote a shift from symptom control towards structure-oriented, disease-modifying comprehensive interventions.
Zhang et al. (Mon,) studied this question.