Circular RNAs (circRNAs) constitute a recently identified class of non-coding RNAs that are widely distributed in eukaryotes. Characterized by the absence of 5' caps and 3' polyadenylated tails, circRNAs may regulate gene expression through multiple mechanisms. Recent studies have shown that certain circRNAs contain binding sites complementary to microRNAs (miRNAs), enabling them to function as molecular sponges that sequester miRNAs and inhibit their suppressive effects on mRNA expression. Emerging evidence indicates that specific circRNAs are involved in the regulation of immune cells and cytokines associated with type 2 chronic rhinosinusitis; however, direct clinical evidence supporting associations between circRNAs and the diagnosis or severity of type 2 chronic rhinosinusitis remains unavailable. In this study, the molecular mechanisms of circRNAs in type 2 inflammation are systematically summarized, established experimental evidence is distinguished from clinical applications that remain to be validated, and a theoretical basis is provided for future research on type 2 chronic rhinosinusitis.

The management of chronic rhinosinusitis (CRS) is frequently complicated by treatment recalcitrance, a phenomenon primarily driven by the persistence of microbial biofilms. Beyond their traditional role as a physical barrier against antibiotics, recent evidence positions biofilms as sophisticated immune modulators that actively perpetuate mucosal dysbiosis. This review synthesizes the pathological continuum of biofilm-associated CRS, elucidating how biofilm derived pathogen associated molecular patterns (PAMPs) trigger the release of epithelial alarmins (TSLP, IL-33, IL-25), thereby fueling a maladaptive Type 2 inflammatory loop. We further examine bacterial survival strategies, such as the formation of small colony variants (SCVs) and intracellular "Trojan Horse" reservoirs, which render conventional functional endoscopic sinus surgery (FESS) and antimicrobial monotherapies insufficient for complete eradication. Crucially, we discuss the current diagnostic disconnect where standard cultures fail to detect biofilm burdens. Finally, we propose a therapeutic paradigm shift from a purely bactericidal approach to one of ecological restoration. By integrating cutting-edge strategies, including matrix-degrading enzymes, bacteriophage cocktails, and Nasal Microbiota Transplantation (NMT), we construct a multi-dimensional framework aiming to restore sinonasal homeostasis. Together, these emerging strategies support a shift from pathogen suppression alone toward ecological and immunologic rebalancing of the sinonasal mucosa, offering a more durable conceptual framework for overcoming treatment recalcitrance.

The advent of biologic therapy for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) has allowed for substantial improvement in symptom control and reduction in medical resource utilization for patients with CRSwNP. CRSwNP is characterized by chronic symptoms (>12 weeks), including nasal congestion, hyposmia or anosmia, anterior or posterior mucopurulent drainage, and, in some patients, facial pain or pressure, with patients also having objective evidence of CRSwNP on nasal endoscopy or imaging. In Western countries, CRSwNP is most frequently marked by type 2 inflammatory cells and mediators, including tissue eosinophilia, T helper type 2 cells, group 2 innate lymphoid cells, locally produced immunoglobulin E, type 2 cytokines, and mast cell activation. Both CRSwNP and aspirin-exacerbated respiratory disease (AERD), an important, severe phenotype of CRSwNP, are associated with impairments in quality of life, medical resource consumption, and recurrent CRSwNP after functional endoscopic sinus surgery (FESS), with some patients requiring revision FESS. There are now four U.S. Food and Drug Administration approved biologics for treatment of CRSwNP, including dupilumab, omalizumab, mepolizumab, and tezepelumab, and more under investigation for the treatment of CRSwNP. Biologics have been shown to decrease nasal polyp size, improve sense of smell, reduce the need for systemic corticosteroids and FESS, and improve quality of life for patients with CRSwNP. In this review, I discuss guidelines for the treatment of CRSwNP and AERD in the biologic era, efficacy of biologic medications, and emerging real-world evidence for the use of biologic therapy for CRSwNP and AERD.