This Editors' Choice issue summarizes six original studies covering: squamous metaplasia in eCRSwNP (n=844 specimens), complement C3 in allergic rhinitis remodeling, PM2.5 and CRS inflammatory endotypes (n=634), gut microbiota in FPIES (n=56 children vs. 43 controls), HA20 clinical phenotypes (n=185 patients, 41 clinics, 7 countries), and COVID-19 vaccine immune memory in antibody-deficient IEI patients.
Key findings across studies: (1) Squamous metaplasia was significantly more prevalent in eCRSwNP vs. non-eosinophilic CRS, and dupilumab reversed IL-4/IL-13–driven epithelial changes in vitro. (2) Complement C3/C3aR signaling drives macrophage lipid reprogramming and TGF-β1–mediated airway remodeling in allergic rhinitis. (3) Higher PM2.5 exposure linked to a mixed type 2/type 3 cytokine endotype (β=1.17, P<0.0001) in CRS patients. (4) FPIES children had reduced *Bifidobacterium* and Verrucomicrobiota vs. healthy controls. (5) HA20 clusters into age-dependent autoinflammatory (children) and autoimmune (adults) phenotypes; TNF/IL-1 inhibitors broadly effective. (6) Most IEI patients with antibody deficiency generated memory B and/or T cells after COVID-19 vaccination despite reduced neutralizing antibody titers.
All six studies are summarized via an editorial overview rather than full-text reporting; individual study limitations (e.g., retrospective design for HA20, single-timepoint microbiota sampling in FPIES, and lack of long-term outcomes for IEI vaccine data) are not detailed here. The CRS/PM2.5 study relies on modeled rather than directly measured pollution exposure.
Clinicians managing eCRSwNP should recognize squamous metaplasia as a common, biologic-reversible remodeling feature—dupilumab may address more than inflammation alone. For IEI patients, COVID-19 vaccination still builds memory B and T cell responses even when antibody titers are low, supporting continued booster strategies and assessment of cellular immunity in this group.
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