Ashish Kumar

Lung inflammation and immune dysregulation are central to the pathogenesis of a broad spectrum of respiratory diseases, yet the cellular and molecular mechanisms underlying these processes remain incompletely understood. This review examines mechanisms of pulmonary inflammation across major respiratory diseases, including asthma, chronic obstructive pulmonary disease, acute lung injury/acute respiratory distress syndrome, and pulmonary fibrosis. We discuss the roles of dysregulated innate and adaptive immunity, persistent inflammation, tissue remodeling, and impaired resolution in the pathogenesis of respiratory diseases, thereby highlighting mechanisms that are broadly conserved across these conditions as well as those that diverge in a disease-specific manner. This synthesis offers a framework for understanding pulmonary immune dysregulation and identifying new biomarkers and therapeutic strategies to restore pulmonary immune homeostasis. We also discuss how endotyping, single-cell transcriptomics, spatial biology, and multi-omics approaches are refining mechanistic understanding and enabling precision immunomodulatory interventions.

This review identifies the menopausal transition as a critical yet underrecognized determinant of asthma heterogeneity in midlife women. It synthesizes evidence that fluctuating sex hormones may shape distinct asthma phenotypes and endotypes, influencing clinical manifestations, disease modifiers, and therapeutic responses. By framing menopause-associated asthma as a biologically distinct, hormone-driven condition, the article highlights key research priorities for precision medicine approaches tailored to women’s respiratory health.

Airway remodeling is a cardinal feature of asthma, associated with increased airway smooth muscle (ASM) cell mass and upregulation of extracellular matrix deposition. Exaggerated ASM cell migration contributes to excessive ASM mass. Previously, we demonstrated the alleviating role of Kp (kisspeptin) receptor (KISS1R) activation by Kp-10 in mitogen (PDGF [platelet-derived growth factor])-induced human ASM cell proliferation in vitro and airway remodeling in vivo in a mouse model of asthma. Here, we examined the mechanisms by which KISS1R activation regulates mitogen-induced ASM cell migration. KISS1R activation using Kp-10 significantly inhibited PDGF-induced ASM cell migration, further confirmed using KISS1R shRNA. Furthermore, KISS1R activation modulated F/G actin dynamics and the expression of promigration proteins like CDC42 (cell division control protein 42) and cofilin. Mechanistically, we observed reduced ASM RhoA-GTPAse with KISS1R activation. The antimigratory effect of KISS1R was abolished by PKA (protein kinase A)-inhibitory peptide. Conversely, KISS1R activation significantly increased cAMP and phosphorylation of CREB (cAMP-response element binding protein) in PDGF-exposed ASM cells. Overall, these results highlight the alleviating properties of Kp-10 in the context of airway remodeling.