CRS burden increased despite improving air quality, with greater allergic and type 2 inflammatory characteristics. Asthma is strongly associated with CRSwNP, while SO2 was independently associated with eosinophilic inflammation.

Asthma and allergic diseases represent a substantial global health burden, frequently compounded by the modern epidemics of obesity and metabolic syndrome to create a complex immunometabolic challenge. The emerging epithelial barrier hypothesis provides a mechanistic framework linking environmental exposures to systemic inflammation and metabolic dysfunction. Standard therapies often fail to address these underlying systemic drivers, particularly in difficult-to-treat phenotypes like obesity-related asthma. This review explores the dual-action potential of glucagon-like peptide-1 receptor agonists (GLP-1RA) as a novel therapeutic strategy. Beyond their established roles in glycemic control and weight loss, GLP-1RA exert direct, weight-independent immunomodulatory effects. Mechanistic evidence demonstrates that the GLP-1 receptor (GLP-1R) is expressed on key immune cells, including eosinophils, macrophages, and Group 2 innate lymphoid cells. Agonism of these receptors suppresses Type 2 (T2) inflammation by reducing cytokine production (IL-5, IL-13) and upstream alarmins (IL-33). Furthermore, GLP-1R signalling enhances regulatory T cell function and may restore epithelial barrier integrity in both the gut and airways. Clinical observations suggest that GLP-1RA initiation improves asthma control and reduces exacerbations, often independently of body mass index reduction. However, prospective trials utilizing specific T2 biomarkers are needed to confirm these direct cellular mechanisms in humans. Transitioning to an immunometabolic approach with GLP-1RA may offer a comprehensive solution for patients at the intersection of metabolic and allergic disease.

Chronic spontaneous urticaria (CSU) remains inadequately controlled by H1-antihistamines and omalizumab in a substantial minority of patients at every age. Recognition that mast cell activation proceeds through IgE-independent as well as IgE-dependent routes has exposed several tractable targets-Bruton's tyrosine kinase, the IL-4/IL-13 axis, KIT, MRGPRX2 and the JAK-STAT pathway-hence the resulting expansion of the treatment armamentarium is the largest since omalizumab. The oral BTK inhibitor remibrutinib is now licensed for adults in the United States and European Union; Dupilumab, approved from 12 years of age in 2025, was extended to children aged 2-11 years in 2026 on basis of extrapolated efficacy supported by paediatric pharmacokinetic and safety data. Barzolvolimab has completed Phase 3 enrolment of 1939 adults, briquilimab, EVO756, EP262 and rilzabrutinib are advancing in adults and ligelizumab failed to demonstrate superiority over omalizumab. This review appraises these agents by mechanism, efficacy, safety and probable place in therapy and argues that the limiting factor is no longer the number of druggable targets but the distribution and quality of the evidence. Adults dominate the trial populations; adolescents are enrolled as underpowered subgroups; dedicated paediatric evidence is essentially confined to dupilumab; and older adults-in whom comorbidity, polypharmacy and the cardiovascular and malignancy signals of JAK inhibition matter most-are almost never analyzed separately. Head-to-head and sequencing trials, endotype-stratified patient selection, age-inclusive trial design and long-term safety data are the immediate priorities if mechanism-based treatment is to reach patients at every stage of life.