Distinct Histopathology Characteristics in Empty Nose Syndrome.

OBJECTIVES/HYPOTHESIS: Empty nose syndrome (ENS) is a controversial disorder and the change of histopathology has never been discussed. This study aimed to conduct a structured histological review to improve the diagnosis and understanding of ENS. Further immunohistochemical staining of transient receptor potential channel melastatin 8 (TRPM8) was performed. STUDY DESIGN: A prospective case-control study in a tertiary medical center. METHODS: Consecutive patients with ENS who were diagnosed and received surgical intervention after failure of conservative management were included. Patients with benign pituitary gland tumor receiving transsphenoidal excision were enrolled as control group. Biopsy of inferior turbinate was obtained during surgery for histological review and immunohistochemical staining. RESULTS: Seventeen patients with ENS and six patients as a control group were established for structured histological review. Patients with ENS presented significantly more squamous metaplasia, a higher rate of submucosal fibrosis, and a lower submucosal gland number grading. Additionally, a unique histological change called goblet cell metaplasia was found in the ENS group. The respiratory epitheliums of ENS were mostly intact with preservation of ciliated cells and goblet cells. The ENS group had a significantly lower expression level of TRPM8. CONCLUSIONS: The nasal mucosa of ENS experienced some airway remodeling and thermoreceptors downregulation, which contribute to clinical symptoms. The distinct histology of ENS included preserved respiratory epithelium and goblet cell metaplasia, accompanying with characteristics similar to atrophic rhinitis. Biopsy of the inferior turbinate may help diagnose ENS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E14-E18, 2021.

Clinical predictors of revision surgery for chronic rhinosinusitis with nasal polyposis within 5-year follow-up.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) remains a difficult-to-cure disease. The aim of this study was to determine the potential long-term predictors of revision sinus surgery for CRSwNP. METHODS: Prospectively gathered patients with bilateral CRSwNP who received primary endoscopic sinus surgery were enrolled. Clinical variables, including the preoperative Lund-Mackay score (LMS), were collected to clarify possible risk factors for revision surgery within a 5-year follow-up. The symptomatic burden was measured using a 10-cm visual analog scale (VAS) before and 1 year after surgery. Further survival analysis was performed to present the revision-free survival in Kaplan-Meier plotting. RESULTS: Eighty four qualified patients were identified and all of them experienced significant improvement in VAS after primary surgery. The 5-year revision rate was 19.05%, and the mean time of revision surgery was 25.31 ± 17.11 months postoperatively. Nasal allergy (OR = 9.287; p = 0.011) and LMS (OR = 1.29; p = 0.06) were found to be the independent risk factors for revision surgery. The discriminatory power of LMS for revision surgery was acceptable (AUC = 0.79) with the best cutoff point located at LMS > 13.5. Patients with both nasal allergy and LMS≧14 had only half of revision-free survival in comparison to overall survival (38.1% vs. 80.95%, p < 0.001). CONCLUSIONS: In patients with CRSwNP who have concurrent nasal allergy and higher preoperative LMS may indicate an advanced disease status and eventually be in a high risk of revision surgery after a long-term follow-up. An outcome-based staging system will be helpful in the future to improve the prognosis for CRSwNP.

Nasal nitric oxide in relation to psychiatric status of patients with empty nose syndrome.

BACKGROUND: Although cases of empty nose syndrome (ENS) are not very common, the suffering that ENS causes patient is immense and could be very difficult to imagine. Nasal nitric oxide (nNO) is an airway disease biomarker, and its levels increase after endoscopic sinus surgery. The trend of nNO levels in ENS before and after surgical treatment remains unknown. This study aimed to evaluate the role of nNO in ENS. METHODS: Patients with ENS who received surgical implantation and with chronic hypertrophic rhinitis (CHR) who underwent turbinoplasty and completed at least 1 year of follow-up were prospectively enrolled. nNO measurements and subjective assessments [SinoNasal Outcome Test (SNOT)-22, Beck Depression Inventory (BDI)-II, and Beck Anxiety Inventory (BAI)] were performed preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: We enrolled 19 ENS and 12 CHR patients. nNO levels were significantly lower in the ENS than in the CHR patients before surgical treatment (p < 0.001). nNO levels in the ENS patients significantly increased 3 months after implantation and remained plateaued (p = 0.015). BDI-II and BAI scores significantly improved after surgical treatment for the ENS patients but not for the CHR patients; changes in nNO levels correlated well with improvements in BDI-II and BAI scores (p = 0.025 and 0.035, respectively). CONCLUSIONS: nNO significantly increased at third month after surgical treatment and remained plateaued in ENS patients. This increase correlated with improvements in BDI-II and BAI scores. Therefore, nNO may be important in assessing the psychiatric status of empty nose syndrome.

Caveolin-1 down-regulation is required for Wnt5a-Frizzled 2 signalling in Ha-RasV12 -induced cell transformation.

Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-RasV12 gene) transformation by Ha-RasV12 . Cav1 overexpression abrogates the Ha-RasV12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells. Nanoparticle tracking analysis showed that Ha-RasV12 -inducing MK4 cells increased exosome-like microvesicles release compared with their normal counterparts. The cellular and mechanical transformation activities of MK4+I-CM were abolished after heat treatment and exosome depletion and were copied by exosomes derived from MK4+I-CM (MK4+I-EXs). Wnt5a, a downstream product of Ha-RasV12 , was markedly secreted by MK4+I-CM and MK4+I-EXs. Suppression of Wnt5a expression and secretion using the porcupine inhibitor C59 or Wnt5a siRNA inhibited the Ha-RasV12 - and MK4+I-CM-induced transformation of MK4 cells and MDCK/shCav1 cells, respectively. Cav1 down-regulation, either by Ha-RasV12 or targeted shRNA, increased frizzled-2 (Fzd2) protein levels without affecting its mRNA levels, suggesting a novel role of Cav1 in negatively regulating Fzd2 expression. Additionally, silencing Cav1 facilitated the internalization of MK4+I-EXs in MDCK cells. These data suggest that Cav1-dependent repression of Fzd2 and exosome uptake is potentially relevant to its antitransformation activity, which hinders the activation of Ha-RasV12 -Wnt5a-Stat3 pathway. Altogether, these results suggest that both decreasing Cav1 and increasing exosomal Wnt5a must be implemented during Ha-RasV12 -driven cell transformation.

Impact of chronic rhinosinusitis on severe asthma patients.

Coexistence of chronic rhinosinusitis (CRS) with asthma appears to impair asthma control. Type-2 innate lymphoid cells (ILC2s) respond to the cytokines of thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, thus contributing to airway diseases such as CRS and asthma. We investigate whether the augmented Th2-cytokines in CRS might be related to sinonasal tract ILC2s corresponding to enhanced IL-25, IL-33 and TSLP release in severe asthmatics, and be involved in asthma control. Twenty-eight asthmatics (12 non-severe and 16 severe) with CRS receiving nasal surgery were enrolled. The predicted FEV1 inversely associated with CRS severity of CT or endoscopy scores. Higher expression of Th2-driven cytokines (IL-4, IL-5, IL-9, and IL-13), TSLP, IL-25 and IL-33 in nasal tissues was observed in severe asthma. Severe asthmatics had higher ILC2 cell counts in their nasal tissues. ILC2 counts were positively correlated with Th2-cytokines. Nasal surgery significantly improved asthma control and lung function decline in severe asthma and CRS. The higher expression of IL-33/ILC2 axis-directed type 2 immune responses in nasal tissue of CRS brought the greater decline of lung function in severe asthma. ILC2-induced the upregulated activity of Th2-related cytokines in asthmatics with CRS may contribute to a recalcitrant status of asthma control.

Evaluation of depression and anxiety in empty nose syndrome after surgical treatment.

OBJECTIVES/HYPOTHESIS: Empty nose syndrome (ENS) is often associated with psychological symptoms. With the absence of psychiatric instruments utilized in the current literature, the assessment of psychological disorder is limited, and the effectiveness of surgical intervention in improving such disorders in ENS are not well understood. The aim of this study was to evaluate the change in depression and anxiety before and after surgical treatment for ENS STUDY DESIGN: Prospective cohort study in a tertiary medical center. METHODS: ENS patients indicated for surgical treatment were enrolled. The Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI) questionnaires were completed by these patients before and after surgery to assess the level of depression and anxiety. RESULTS: A total of 20 patients completed the BDI-II and BAI before and after surgical treatment. A majority of patients developed depression and anxiety prior to surgical treatment. The severity of depression and anxiety were significantly decreased following the surgery; the mean scores of both the BDI-II and BAI improved from moderate severity to normal (both P < .001). The preoperative total score was found to be a powerful predictor for the postoperative improvement in both BDI-II and BAI (P < .001). Female patients had significantly worse preoperative scores (P = .005) and greater postoperative improvement (P = .012) in the BDI-II. CONCLUSIONS: Depression and anxiety are psychological disorders prevalent among ENS patients. Surgical treatment for ENS is effective in improving depression and anxiety. Patients with worse preoperative BDI-II and BAI scores as well as female patients may be better candidates for surgical intervention. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1284-1289, 2016.