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Objectives: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes. Methods: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators. Results: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months. Conclusion: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5. [ABSTRACT FROM AUTHOR]

Background: Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. Objective: We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma. Methods: We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund–Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications. Results: FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P <.05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P <.001) and FEV1/FVC (r = −0.324, P =.001). A FeNO level of 27 ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68 ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36 ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%). Conclusion: FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a multifactorial disease characterized by long-term inflammation of the nasal and sinus passages. Neo-osteogenesis which is a major finding of recalcitrant CRS is clinically related to the disease severity and surgical outcomes of CRS. The immunological and molecular mechanisms underlying neo-osteogenesis of CRS remain unclear, and many recent studies have suggested the importance of inflammatory mediators secreted by immune cells. This paper provides a broader understanding of neo-osteogenesis in CRS by reviewing recent updates and evidence of the association between CRS pathophysiology and neo-osteogenesis. Crosstalk between the bone and mucosa eventually results in refractory CRS. In addition, both eosinophilic and non-eosinophilic CRS cytokines can play a role in neo-osteogenesis and trigger an enhanced CRS-associated immune response. The significance of predicting neo-osteogenesis in advance or during postoperative care could be essential for effectively managing refractory CRS and enhancing the prognosis of CRS patients. [ABSTRACT FROM AUTHOR]

Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases. [ABSTRACT FROM AUTHOR]

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects. [ABSTRACT FROM AUTHOR]

[Display omitted] Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear. This study aimed to investigate the influence of NETs on the CRS epithelium. Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63+ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model. NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63+ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67+p63+ cells. We found that ΔNp63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ΔNp63+ epithelial stem cells and reduced polyp formation. These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs. [ABSTRACT FROM AUTHOR]

Background: Studies on the pathophysiology of nasal polyps in human subjects have been limited; thus an animal model is needed. There is increasing evidence supporting the role of Staphylococcus aureus enterotoxin B (SEB) in the pathogenesis of nasal polyposis. The aim of this study was to investigate the histological and immunologic effects of SEB on the formation of nasal polypoid lesions in an allergic rhinosinusitis murine model. Methods: After induction of an ovalbumin (OVA)-induced allergic rhinosinusitis, OVA with SEB (5 or 500 ng) was instilled into the nasal cavity of mice for 8 weeks. Control mice did not receive SEB or OVA instillation. Histopathological changes were observed using hematoxylin and eosin, Sirius red, Giemsa, Masson's trichrome, and Alcian blue stains. The levels of interleukin (IL)-4, IL-5, IL-8, IL-13, eotaxin, interferon gamma, total IgE, and OVA-specific IgE from serum or nasal lavage fluid were measured using enzyme-linked immunosorbent assay. Results: The group treated with OVA plus 5 ng of SEB had significantly more mucosal lesions with epithelial disruption and nasal polypoid lesions than mice treated with OVA only, showing a significant increase in the infiltration of total inflammatory cells, eosinophils, and lymphocytes than the other groups. Levels of IL-5, eotaxin, and OVA-specific IgE in nasal lavage fluid were increased in the group treated with OVA plus 5 ng of SEB than in the other groups. A higher number of secretory cells in the groups treated with OVA plus SEB was observed than in other groups. Conclusion: Low-dose SEB induced nasal polypoid lesions with an increased eosinophilic infiltration in an allergic rhinosinusitis murine model. [ABSTRACT FROM AUTHOR]

Background: Preoperative inflammation of the olfactory cleft may cause not only the obstruction of this area, but also damage of the olfactory neuroepithelium, resulting in anosmia. Therefore, the evaluation of the affected olfactory cleft by computed tomography (CT) might help predict postoperative olfaction. Methods: Fifty-two patients who underwent functional endoscopic sinus surgery for chronic rhinosinusitis (CRS) with nasal polyps were examined preoperatively and at 6 months after surgery. OMU CT was obtained preoperatively and olfactory function tests such as the butanol threshold test, the cross-cultural smell identification test, and questionnaires were performed at the initial preoperative visit and at 6 months after surgery. The correlation between the status of the olfactory cleft on CT and the postoperative olfactory results were investigated. Results: The findings of olfactory cleft opacification and the CT scores had a negative correlation with preoperative olfactory results (p < 0.05). The olfactory cleft opacification showed a stronger correlation with the preoperative olfactory results than the CT score. The total olfactory cleft opacification score and anterior olfactory cleft opacification score (AOCS) were more significantly correlated with the postoperative olfactory results than the other parameters (p < 0.05). Among the CT findings, the AOCS was a significant prognostic factor of olfactory results after surgery; these findings were significant on multiple regression analysis (p < 0.05). The postoperative olfactory scores and the improvement of olfactory scores after surgery were increased more in the mild AOCS group than in the moderate and severe AOCS groups (p < 0.05). Recovery and normosmia rates were much better in the mild AOCS group in this study (p < 0.05). Conclusion: Preoperative CT findings, especially the anterior portion of the olfactory cleft, had a statistically significant association with the postoperative olfactory results in patients with CRS with nasal polyps. [ABSTRACT FROM AUTHOR]

Background: This study investigated the efficacy of glove finger-coated polyvinyl acetate (PA) pack on hemostasis, pain levels, and wound healing after endoscopic sinus surgery (ESS). Methods: A prospective, randomized, double-blinded controlled study was performed in 30 patients who underwent bilateral ESS for chronic rhinosinusitis. Fifteen patients (control group) had both nasal cavities packed with PA pack (Merocel; Medtronic Xomed, Jacksonville, FL) and another 15 subjects (experimental group) had their nasal cavities packed with PA in a glove finger. Pain levels were assessed by patients on a visual analog scale 12 hours after surgery and at the time of packing removal. The amount of bleeding on removal were quantified by weighing it after removal. Lund-Kennedy score and synechiae formation were assessed at 4, 8, and 12 weeks after surgery. The use of analgesics and oral steroid was compared between the two groups. Results: The experimental group showed lower levels of pain and lessened bleeding during packing removal than the control group. There were no differences in pain levels at 12 hours after surgery, use of analgesics and oral steroid between the two groups. One (6%) of each group had postoperative bleeding and required additional packing for hemostasis. Lower Lund-Kennedy score at postoperative 4 weeks was documented in the experimental group. In addition, two (13%) control subjects developed a synechiae between the middle turbinate and the lateral wall. Conclusion: PA packing in a glove finger is advantageous in terms of pain, bleeding on packing removal, and postoperative wound healing, compared with PA pack only. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific IgE predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in nonasthmatic patients. We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) Vβ (TCRVβ) in nonasthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion. Sinonasal tissue samples were obtained from patients with nonasthmatic chronic rhinosinusitis (CRS) with NPs (CRSwNP), patients with CRS without NPs (CRSsNP), and control subjects. SAE genes were detected by PCR, and the TCRVβ distribution and T-cell phenotypes were examined by flow cytometry. Various SAE genes were detected not only in NPs but also in sinonasal mucosa from patients with CRSsNP and from controls. The S aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI–responsive TCRVβ+ (TCRVβ1+ and Vβ5.1+) CD4+ T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRVβ5.1+ CD4+ T cells expressed proliferation marker Ki-67 and the T H 2 transcription factor GATA3. Furthermore, TCRVβ5.1+ CD4+ T cells in NPs highly expressed T H 2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor–homologous molecule expressed on T H 2 cells, with a potent T H 2 cytokine–producing ability. Moreover, the expansion of TCRVβ1+ or Vβ5.1+ CD4+ T cells was associated with the Lund-Mackay computed tomography score, indicating disease extent. In nonasthmatic patients with CRSwNP, superantigen-related expansion of CD4+ T cells with T H 2 differentiation was associated with the disease extent. [ABSTRACT FROM AUTHOR]

Objective: The recurrence of chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS) is influenced by various factors, potentially including the endotype based on the molecular pathophysiology of CRS. This study investigated differences in the recurrence pattern of CRS by endotype after primary FESS.Methods: This retrospective study enrolled patients who had undergone revision FESS for recurrent CRS. Based on their clinical diagnosis, the patients were divided into two endotype groups: recurrent eosinophilic CRS (rECRS) and recurrent non-eosinophilic CRS (rNECRS). We compared and analyzed preoperative computed tomography (CT) findings, including typical anatomical findings of recurred CRS such as lateralized middle turbinate and retained uncinate process, the sinus where recurrence took place, and previous surgical completeness of the sinuses, between the rECRS and rNECRS groups.Results: In total, 142 patients were enrolled (48 rECRS, 94 rNECRS). No significant difference was found in the typical anatomic findings of recurrent CRS between the rECRS and rNECRS groups. The rates of the completeness of previous surgeries was significantly higher in rECRS than in rNECRS(P=.031). Despite the completeness of previous surgeries, the recurrence rate of frontal and ethmoidal sinuses was higher in the rECRS than rNECRS(P=.012, P<.001, respectively). In subgroup analysis according to the severity of ECRS, the number of involved sinuses and the rates of CRS recurrence and surgical completeness in frontal and anterior ethmoidal sinuses increased with ECRS severity.Conclusions: CT findings of revision FESS cases differed by CRS endotype. The rECRS group showed higher recurrence in the frontal and ethmoidal sinuses despite a higher surgical completeness rate. Incomplete surgery was more often found in the rNECRS group. [ABSTRACT FROM AUTHOR]

Background: Evidence of osteitis is frequently observed in patients with chronic rhinosinusitis (CRS), especially in recalcitrant cases. However, studies focusing on biological markers of osteitis are limited and it remains unclear whether osteitis is associated with different phenotypes of CRS. This study aimed to analyze the expression and assess the roles of receptor activator of nuclear factor κB ligand (RANKL) in patients with CRS and osteitis. Methods: CRS patients with nasal polyps (CRSwNP, n = 63), CRS patients without nasal polyps (CRSsNP, n = 8), and control subjects (n = 12) were enrolled. Histologic phenotypes, clinical information, and computed tomography (CT) scores were investigated. The Global Osteitis Scoring Scale (GOSS) and RANKL, a molecular marker of bone remodeling, were analyzed in each type of CRS. CRS mouse models were treated with anti‐RANKL. Results: GOSS values were significantly higher in all CRS patients than in the control group. The GOSS value in non‐eosinophilic CRSwNP was higher than in eosinophilic CRSwNP. RANKL was upregulated whereas decoy receptor osteoprotegerin (OPG) was downregulated in CRS. RANKL messenger RNA (mRNA) and protein levels were positively correlated with GOSS. RANKL/OPG was increased in recurrent cases compared with primary cases. Multiple inflammatory mediators were positively correlated with the protein level of RANKL in CRS tissues. In the mouse CRSwNP model, anti‐RANKL treatment abrogated mucosal inflammation and bone remodeling. Conclusion: RANKL expression is associated with clinical osteitis and disease severity in CRSwNP. These findings shed light on the importance of RANKL as a potential biomarker of CRS and a key player in CRS pathogenesis. [ABSTRACT FROM AUTHOR]