The Burden of Chronic Rhinosinusitis Without Nasal Polyps: A Systematic Review of Epidemiological, Clinical,...

Chronic rhinosinusitis (CRS) is a heterogeneous and often debilitating disease characterized by persistent sinonasal symptoms and inflammation and is phenotypically classified as CRS with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP). Although CRSsNP is the more prevalent phenotype (approximately 80%), it remains disproportionately understudied, leading to critical gaps in understanding and management. This systematic literature review synthesized current global evidence on the epidemiological, clinical, humanistic, and economic burden of CRSsNP, highlighting areas of unmet need and raising awareness of the impact of this disease. PRISMA-compliant searches were conducted for CRSsNP records published 2004-2024 (epidemiological studies 2014-2024) across six electronic databases. Targeted hand searches were performed for abstracts (2022-2024), health technology assessments, guidelines, and clinical trial registries. Of 2215 records identified, 157 met inclusion criteria. CRSsNP prevalence was 4.3-10.4% in the USA, South Korea, and Spain. Patients experienced a range of symptoms including nasal/sinus (obstruction, discharge, crusting), pain, sensory (anosmia, cacosmia), respiratory (cough, asthma), oral (dry throat, halitosis), and sleep impairment. There was considerable variability in the availability and use of tools to assess severity; this impeded cross-study comparisons, consistent disease staging, and treatment escalation criteria. Associated comorbidities included asthma, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and primary antibody deficiencies. Humanistic burden was assessed using a variety of outcome measures and was higher for patients with CRSsNP than for controls. Limited data were available on economic burden. Currently available therapies were associated with high rates of treatment failure, inadequately controlled symptoms, and the need for multiple lines of therapy. CRSsNP is associated with considerable burden across clinical, humanistic, and economic domains, exacerbated by diagnostic variability, treatment limitations, and a lack of standardized research methodologies. This highlights the need for coordinated efforts among stakeholders to better address this chronic condition and support future improvements in patient outcomes.