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Open research questions in Sinusitis and nasal conditions

420 gap statements mined from Sinusitis and nasal conditions papers in our 7.9M-paper local library, which holds 2,161 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The treatment selection for patients with both asthma and sinonasal diseases is not well refined. The long-term effects of biologic therapy across the upper and lower airways are not fully evaluated.

    Asthma and Sinonasal Diseases: Shared Clinical Comorbidities, Inflammatory Pathways and Management Strategies · 2026 · DOI

  • The extent of prior endoscopic sinus surgery in patients with chronic rhinosinusitis is unknown. There is a need to investigate this extent in patients referred to tertiary care rhinologic clinics.

    Assessment of the extent of previous endoscopic sinus surgery using the ACCESS score in patients with chronic rhinosinusitis referred to tertiary care rhinologic clinics · 2026 · DOI

  • Real-world comparative data across all approved biologics for chronic rhinosinusitis with nasal polyps remain limited. Randomized controlled trials may not fully capture treatment effectiveness in daily clinical practice.

    Biologics for chronic rhinosinusitis with nasal polyps: a real-world prospective cohort study · 2026 · DOI

  • The study also notes that clinical presentation may vary by age, making diagnosis and treatment challenging. The study identifies the need for improved understanding of the development of CRS from childhood to adulthood to improve early diagnosis and treatment.

    Chronic rhinosinusitis in a birth cohort: symptom trajectories and early-life risk factors up to young adulthood · 2026 · DOI

  • There is limited information on the development of CRS from childhood to adulthood in the general population. The study aims to fill this gap by investigating the development of upper airway symptoms from childhood to young adulthood and identifying early risk factors for CRS.

    Chronic rhinosinusitis in a birth cohort: symptom trajectories and early-life risk factors up to young adulthood · 2026 · DOI

  • Limited access to the studied tissue. Lack of available biomarkers. Difficulty in collecting a large series of specimens from patients with CRS and healthy controls.

    Chronic Rhinosinusitis—Microbiological Etiology, Potential Genetic Markers, and Diagnosis · 2024 · DOI

  • Although local dysregulation of coagulation and fibrinolysis is implicated in ECRS pathogenesis, it remains unclear whether these abnormalities involve systemic hemostatic changes.

    Distinct peripheral coagulation–fibrinolysis profiles in eosinophilic and non-eosinophilic chronic rhinosinusitis · 2026 · DOI

  • The leukocyte immunoglobulin-like receptor (LILR) family plays a critical role in maintaining mast cell and eosinophil homeostasis; however, their involvement in ECRS remains unclear.

    Downregulation of leukocyte immunoglobulin-like receptor B3 is involved in eosinophilic rhinosinusitis · 2026 · DOI

  • Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by epithelial barrier dysfunction and type 2-dominant inflammation, yet the upstream regulatory mechanisms linking epithelial remodeling and immune activation remain poorly understood, and reliable biomarkers for eosinophilic CRSwNP (EOS CRSwNP) are limited.

    S1P/S1PR3 axis drives epithelial dysfunction and type 2 inflammation in chronic rhinosinusitis with nasal polyps · 2026 · DOI

  • Although allergic rhinitis (AR) commonly co-occurs with chronic rhinosinusitis with nasal polyps (CRSwNP), its impact on tissue endotypes and prognosis remains unclear.

    The Association Between Allergic Rhinitis, Eosinophilic Inflammation, and Postoperative Recurrence in Nasal Polyps · 2026 · DOI

  • While sinonasal inflammation and anatomy are known to be affected by obesity, its impact on symptom severity and objective imaging findings remain unknown.

    Effect of Body Mass Index on Sinonasal Symptoms and Imaging Results · 2026 · DOI

  • Recent single-cell studies have highlighted fibroblast subsets contributing to T2 inflammation; however, the role of fibrocytes remains unclear.

    Fibrocytes as Key Mediators of Type 2 Inflammation in Asian Chronic Rhinosinusitis With Nasal Polyps · 2026 · DOI

  • Exhalation delivery system with fluticasone (EDS-FLU) is approved for CRS; however, the influence of these features on treatment response remains unclear.

    Exhalation delivery system with fluticasone in chronic rhinosinusitis by eosinophil count and asthma and allergy status · 2026 · DOI

  • Recurrence remains common in eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) despite surgery and type 2-directed therapy, suggesting that epithelial injury mechanisms beyond cytokine signaling remain incompletely defined.

    Elevated EZH2 expression is associated with reduced NRF2-related antioxidant signaling and ferroptosis-associated features in eosinophilic chronic rhinosinusitis with nasal polyps · 2026 · DOI

  • However, the relationship between ANS dysfunction and chronic rhinosinusitis (CRS) has not been fully investigated.

    A positive correlation between autonomic nervous system function and endoscopic disease severity in chronic rhinosinusitis: a quantitative assessment · 2026 · DOI

  • BACKGROUD: The efficacy of tezepelumab in chronic rhinosinusitis with nasal polyps (CRSwNP) has been demonstrated in clinical trials, but real-world evidence remains limited.

    Upper and lower airways response to tezepelumab in asthma patients with / without comorbid nasal polyposis: a 6-months reallife perspective · 2026 · DOI

  • Real-world data is needed to establish effectiveness in uncontrolled severe CRSwNP, but so far, data on long-term omalizumab treatment is sparse.

    Real-world effectiveness of omalizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP): findings from CHRINOSOR · 2026 · DOI

  • Ciliary abnormalities are implicated in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), but whether these changes are site-specific traits or confined to specific cell populations remains unknown.

    The elongated ciliated cells derived from nasal polyps are distinctly different from ciliated cells in different parts of the nasal mucosa · 2026 · DOI

  • Currently, real-world efficacy (RWE) data of dupilumab in patients who switch to dupilumab after having no or minimal therapeutic response to either omalizumab or mepolizumab are lacking.

    Real world efficacy of dupilumab in switchers versus biological naive CRSwNP patients · 2026 · DOI

  • Recent findings suggest the interaction between local IgE and mast cells in nasal polyps (NPs) is key to eCRS pathogenesis; however, the details remain unclear.

    Elevated MS4A2 and IgE interaction in nasal polyps contributing to poor postoperative prognosis in patients with eosinophilic chronic rhinosinusitis · 2025 · DOI

  • However, its expression and functions in chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear.

    M2 macrophage-derived Apolipoprotein E promotes fibroblast MMPs expression via LRP1-ERK signaling in chronic rhinosinusitis with nasal polyps · 2025 · DOI

  • These findings suggest that fibrocytes may be a previously underrecognized T2 cytokine-producing population in CRSwNP, and that fibrocytes, together with T cells, may be key drivers of type 2 inflammation and represent potential therapeutic targets in Asian patients with CRSwNP.

    Fibrocytes as Key Mediators of Type 2 Inflammation in Asian Chronic Rhinosinusitis With Nasal Polyps · 2026 · DOI

  • Pediatric chronic rhinosinusitis with nasal polyps (CRSwNP) exhibits a high rate of postoperative recurrence, yet the histopathological determinants are not well defined.

    Histopathological Signatures Associated With Postoperative Recurrence in Pediatric Chronic Rhinosinusitis With Nasal Polyps · 2026 · DOI

  • Data supporting the efficacy of reslizumab in CRSwNP remain not definitive for regulatory approval for this indication, - The pathophysiological link between DMII and asthma remains unclear, - The study only reviewed literature from 2000…

    Asthma and Sinonasal Diseases: Shared Clinical Comorbidities, Inflammatory Pathways and Management Strategies · 2026 · DOI

  • Further studies are needed to confirm the long-term effectiveness and safety of biologics in CRSwNP, - Comparative effectiveness data in different populations and settings are needed, - Research on the optimal treatment strategy and patient selection criteria for biologics in CRSwNP…

    Biologics for chronic rhinosinusitis with nasal polyps: a real-world prospective cohort study · 2026 · DOI

Most-cited papers in Sinusitis and nasal conditions

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Open questions raised by papers listed on this page include: (1) The long-term effects of biologic therapy across the upper and lower airways are not fully evaluated (“Asthma and Sinonasal Diseases: Shared Clinical Comorbidities, Inflammatory…”, 2026); (2) The extent of prior endoscopic sinus surgery in patients with chronic rhinosinusitis is unknown (“Assessment of the extent of previous endoscopic sinus surgery using the ACCESS…”, 2026); (3) Real-world comparative data across all approved biologics for chronic rhinosinusitis with nasal polyps remain limited (“Biologics for chronic rhinosinusitis with nasal polyps: a real-world…”, 2026); (4) There is limited information on the development of CRS from childhood to adulthood in the general population (“Chronic rhinosinusitis in a birth cohort: symptom trajectories and early-life…”, 2026); (5) Although local dysregulation of coagulation and fibrinolysis is implicated in ECRS pathogenesis, it remains unclear whether these abnormalities involve systemic hemostatic changes (“Distinct peripheral coagulation–fibrinolysis profiles in eosinophilic and…”, 2026). 420 gap statements have been mined from Sinusitis and nasal conditions papers in our 7.9M-paper local library, which holds 2,161 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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