Inflammatory Factors and Chronic Rhinosinusitis: An Umbrella Review

Area of Science:

• Immunology
• Otolaryngology
• Respiratory Medicine

Background:

• Chronic rhinosinusitis (CRS) is a prevalent inflammatory condition affecting nasal passages and sinuses.
• CRS presents with heterogeneous clinical features and underlying mechanisms, complicating classification and treatment.
• Two main phenotypes exist: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP).

Purpose of the Study:

• To review and synthesize evidence on the distinct inflammatory pathways and immune patterns in CRS.
• To explore the heterogeneity of CRS endotypes and their clinical implications.
• To assess the potential of endotype-driven management and biologic therapies.

Main Methods:

• An umbrella review was conducted following PRISMA guidelines.
• Systematic literature searches were performed in Scopus and PubMed.
• 64 studies published from May 1968 to August 2025 were included and findings synthesized qualitatively.

Main Results:

• CRS inflammation involves distinct T helper cell (Th1, Th2, Th17, Th22) and T regulatory cell (Treg) patterns.
• Type 1 inflammation (often in CRSsNP) features interferon-gamma, IL-12, and neutrophilic infiltration.
• Type 2 inflammation (common in CRSwNP) involves TSLP, IL-25, IL-33, Th2 cytokines, and eosinophils, impacting mucus production and epithelial transport.
• Type 3 (Th17) inflammation is linked to IL-17, IL-22, and host defense against microbes.

Conclusions:

• Inflammatory pathways in CRS are diverse and can overlap, influencing disease phenotypes.
• Comorbidities like aspirin-exacerbated respiratory disease and cystic fibrosis impact CRS endotypes.
• Endotype-driven management, including biologic therapies like dupilumab, shows promise but requires further refinement for optimal patient stratification and treatment selection.