WDPCP regulates the ciliogenesis of human sinonasal epithelial cells in chronic rhinosinusitis.

Damage to the mucociliary clearance system is a typical change in the pathogenesis in chronic rhinosinusitis. However, the mechanisms underlying cilia loss remain unclear. WDPCP is a key protein essential for ciliogenesis, and is also an effector of the planar cell polarity signaling system. In this study, we sought to determine the role of WDPCP in cilia loss in patients with chronic rhinosinusitis. We demonstrated the expression of WDPCP in human sinonasal epithelium from patients with chronic rhinosinusitis and control subjects. We also used air-liquid interface to culture primary human sinonasal epithelial cells in-vitro model and to investigate WDPCP function. We then explored links between rhinosinusitis, WDPCP and inflammation. Accompanied with cilia loss, expression of WDPCP in human sinonasal epithelium from patients with chronic rhinosinusitis was decreased significantly compared with control subjects. In vitro study, we found that WDPCP level increased at first, and then decreased. Inhibiting WDPCP expression could lead to the poor quantity and length of cilia with reduced expression of Septin7. Also, Th1 type inflammatory mediators could decrease the expression of WDPCP. In conclusion, inflammatory cytokines cause reduced WDPCP expression, which contributes to impaired ciliogenesis in human rhinosinusitis.

Extensive versus functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps and asthma: A 1-year study.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is considered to be the standard procedure for chronic rhinosinusitis with nasal polyps (CRSwNP). However, for CRSwNP that accompanies asthma, the results are not satisfying. Extensive endoscopic sinus surgery (EESS) aimed at reducing the inflammatory load has been indicated as a viable option for refractory chronic rhinosinusitis. OBJECTIVE: To evaluate the clinical outcomes and safety of EESS (middle turbinate and superior turbinate resection and total ethmoidectomy) for patients with CRSwNP and with asthma. METHODS: This was a prospective, single-institute cohort study conducted in a tertiary teaching hospital. Patients with CRSwNP and with asthma who were proceeding to surgery were enrolled. There were 23 patients in the EESS group and 24 patients in the FESS group. The preoperative disease severity was evaluated by the visual analog scale (VAS), Lund-Kennedy (L-K) endoscopy score, computed tomography Lund-Mackay score, asthma control test (ACT), and pulmonary function test. Clinical outcomes were comparatively evaluated between the two groups after a 1-year follow-up by using the VAS score, the postoperative endoscopic score (E score), L-K score, ACT score, and pulmonary function test. RESULTS: The disease severity (general VAS score, endoscopic L-K score, computed tomography score, ACT score) showed no significant differences between the two groups before surgery (p > 0.05). One year after surgery, both groups achieved significant improvement in the VAS score and endoscopic L-K score. The EESS group showed better improvement in the olfactory VAS score and E score compared with the FESS group (mean [standard deviation] change of olfactory VAS, 6.00 ± 3.67 versus 3.30 ± 3.44, p = 0.015; mean [standard deviation] E score, 0.31 ± 0.18 versus 0.66 ± 0.26, p < 0.001). No significant differences were found in the change of general nasal symptom VAS score, other individual VAS scores (nasal congestion, discharge, headache and/or facial pain), L-K score, ACT score, and pulmonary function between the two groups (p > 0.05). CONCLUSION: EESS for patients with CRSwNP and with asthma may help to improve the subjective olfaction and endoscopic appearance.

Connexin 43 Upregulation in Mouse Lungs during Ovalbumin-Induced Asthma.

BACKGROUND: Connexin (Cx)-based gap junction channels play important roles in the inflammatory response. Cx43 is involved in the pathogenesis of some lung diseases such as acute lung injury. However, the Cx43 expression in asthma is unclear. In the present study, we used a murine model of ovalbumin (OVA)-induced allergic airway disease to examine the levels of Cx43 and analyze the relationship between Cx43 and airway inflammation in allergic airway disease. METHODS: Asthma was induced in mice via sensitization and challenge with OVA. Cx43 mRNA and protein expression levels were investigated via QT-PCR, western blot, and immunohistochemistry 0 h, 8 h, 1 d, 2 d and 4 d after the first challenge. The relationship between Cx43 protein levels and inflammatory cell infiltration, cytokine levels was analyzed. RESULTS: The OVA-induced mice exhibited typical pathological features of asthma, including airway hyper-responsiveness; strong inflammatory cell infiltration surrounding the bronchia and vessels; many inflammatory cells in the bronchoalveolar lavage fluid (BALF); higher IL-4, IL-5 and IL-13 levels; and high OVA specific IgE levels. Low Cx43 expression was detected in the lungs of control (PBS) mice. A dramatic increase in the Cx43 mRNA and protein levels was found in the asthmatic mice. Cx43 mRNA and protein expression levels increased in a time-dependent manner in asthma mice, and Cx43 was mostly localized in the alveolar and bronchial epithelial layers. Moreover, lung Cx43 protein levels showed a significant positive correlation with inflammatory cell infiltration in the airway and IL-4 and IL-5 levels in the BALF at different time points after challenge. Interestingly, the increase in Cx43 mRNA and protein levels occurred prior to the appearance of the inflammatory cell infiltration. CONCLUSION: Our data suggest that there is a strong upregulation of Cx43 mRNA and protein levels in the lungs in asthma. Cx43 levels also exhibited a positive correlation with allergic airway inflammation. Cx43 may represent a target to treat allergic airway diseases in the future.

Corticosteroid regulates epithelial occludin expression in nasal polyps through a MKP-1-dependent pathway.

OBJECTIVE: To evaluate the regulatory effect of corticosteroid on occludin expression in polyp tissues of chronic rhinosinusitis with nasal polyps (CRSwNP) patients and in vitro. METHODS: Twenty CRSwNP patients were enrolled and subjected to prednisone (30 mg/day for 14 days). The expression of occludin in polyp tissues was examined before and after treatment using immunohistochemical staining and quantitative reverse transcription polymerase chain reaction. Moreover, the expression of occludin in polyp-derived epithelial cells (PECs) and human bronchial epithelial cells (BECs) was examined using Western blot analysis in the presence of corticosteroid and/or MKP-1 siRNA, respectively. RESULTS: mRNA and protein expression of occludin in polyp tissues was significantly upregulated after prednisone administration (p < 0.05). Corticosteroids significantly increased MKP-1 and occludin expression in cultured PECs (p < 0.05), and MKP-1 siRNA significantly decreased occludin expression in cultured BECs (p < 0.05). CONCLUSION: Our findings suggest that corticosteroid can promote epithelial occludin expression in nasal polyps through a MKP-1-dependent pathway.

[Expression and regulation of tight junction protein Occludin in nasal polyps].

OBJECTIVE: To evaluate the possible role of tight junction protein Occludin in nasal polyps. METHODS: The expression of Claudin-1, Occludin and ZO-1 in nasal polyps (n = 20) and healthy uncinate mucosa (n = 15) were examined using immunohistochemical staining, real-time quantitative polymerase chain reaction (PCR) and Western blot analysis. The regulatory effects of proinflammatory cytokines (IFN-γ, IL-13, IL-17, TGF-ß, TGF-α) on the expression of Occludin in cultured human nasal epithelial cells were investigated. RESULTS: The immunohistochemical results showed that Claudin-1, Occludin and ZO-1 were detected both in the nasal polyp group and the control group. The expression sites were the cell membrane and cytoplasm of nasal mucosa epithelial cells. The mean optical density of Claudin-1, Occludin and ZO-1 were 0.187 ± 0.076,0.172 ± 0.109 and 0.098 ± 0.035 respectively in the nasal polyp group and were significantly lower than those in the control group (0.312 ± 0.101, 0.220 ± 0.069 and 0.233 ± 0.093 respectively), the differences were significant (t = 9.345, t = 3.301, t = 13.323, all P < 0.01).RT-PCR results showed that the relative expression of Occludin mRNA was 0.000 117 ± 0.000 035 in the nasal polyp group and was significantly lower than that in the control group(0.000 464 ± 0.000 134), and the difference was significant (Z = -5.0, P < 0.01) . There was no statistically significant difference in the relative expression of Claudin-1 and ZO-1 mRNA between the nasal polyp group and the control group (P > 0.05) . After the cultured human nasal epithelial cells were stimulated by IL-13, IL-17, IFN-γ and other proinflammatory cytokines, the relative expression of Occludin mRNA was 0.631 ± 0.039, 0.581 ± 0.029 and 0.648 ± 0.040, respectively. Compared with the unstimulated control group, the differences were statistically significant (t = 16.299, 24.669 and 14.995 respectively, all P < 0.05).Western blot analyse showed that the relative grayscale in the above proinflammatory cytokines stimulation groups was 0.650 ± 0.061,0.482 ± 0.106 and 0.536 ± 0.109, respectively. Compared with the unstimulated control group, the differences were statistically significant (t = 9.880, 8.442 and 7.310 respectively, all P < 0.05). CONCLUSIONS: The reduced expression of Occludin might be involved in the pathogenesis of nasal polyps.

A modified surgical procedure for endoscopic optic nerve decompression for the treatment of traumatic optic neuropathy.

BACKGROUND: Although the endoscopic anterior-to-posterior technique offers many advantages, the long-term effects of the iatrogenic trauma (removal of the uncinate process and anterior ethmoidal sinus) resulting from the complete ethmoidectomy procedure used to gain full access to the optic nerve canal is unknown, and sequelae such as nasal synechia and sinusitis should not be ignored. AIMS: The aim of our study is to develop a less invasive procedure for endoscopic optic nerve decompression. MATERIALS AND METHODS: We proposed a modified trans-sphenoidal surgical procedure for endoscopic optic nerve decompression in five patients with traumatic optic neuropathy (TON), all with high sphenoidal pneumatisation and without Onodi cellulae. RESULTS: After performing a direct sphenoidotomy through the natural ostium of the sphenoid sinus rather than a complete ethmo-sphnoidectomy, we found that the modified approach provided adequate access to the optic nerve canal and the apex using a 45° angled endoscope. Successful decompression of the canal optic nerve was performed trans-sphenoidally in all five TON patients using an angled endoscope. No surgical complications occurred, and none of the patients suffered from anterior ethmoidal sinus or skull base damage. CONCLUSIONS: The modified trans-sphenoidal approach is a feasible, safe, effective, and minimally invasive approach for TON patients with high sphenoidal pneumatisation and without supersphenoid-ethmoid cellulae.

Clinical characteristics and surrogate markers of eosinophilic chronic rhinosinusitis in Southern China.

The surrogate markers for subclassifying eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS remain elusive. We herein performed a cross-sectional study to assess the clinical implication of clinical symptoms, CT findings, blood eosinophil (EOS) examination based on histological examination of tissue eosinophilia in 105 adult CRS patients (including 72 with nasal polyps and 33 without nasal polyps) in southern China. We found the mean score of smell loss was significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05), whereas the average ethmoid osteitis index in non-ECRS subgroup was significantly higher than that in ECRS subgroup (p < 0.05). Moreover, we found both the mean blood EOS number and ratio were significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05). By applying receiver operating characteristic (ROC) curve analysis, we found blood EOS number had a sensitivity of 84.9 % and specificity of 84.4 % [area under the curve (AUC): 0.873] at the cutoff level of 0.16 × 10(9)/L, and blood EOS ratio had a sensitivity of 89.0 % and specificity of 84.4 % (AUC: 0.863) at the cutoff level of 2.05 % in this cohort. Our findings indicated that smell loss score, ethmoid osteitis index and blood EOS number and ratio may be used for the differential diagnosis of ECRS as the surrogate markers.

Modified laryngotracheal separation for intractable aspiration pneumonia in patients with nasopharyngeal carcinoma treated by radiotherapy.

OBJECTIVES: Intractable aspiration pneumonia in patients with post-radiotherapeutic nasopharyngeal carcinoma (PNC) is a formidable complication, but has not attracted enough attention in clinical practice. Modified laryngotracheal separation (MLTS) was applied for these patients in our hospital, the surgical effects of which were assessed. PATIENTS AND METHODS: Retrospective analysis of 9 PNC cases complicated by intractable aspiration pneumonia in our hospital was carried out. All cases were diagnosed as lower cranial nerve palsy. Their aspiration pneumonia was not effectively prevented or controlled after a series of previous treatments, including active anti-infectives, neurotrophy, acupuncture, nutrition support, nasogastric feeding and tracheotomy. Ultimately all of them received modified laryngotracheal separation (MLTS) surgery. Efficacy of the operation was assessed. RESULTS: In all patients, aspiration pneumonia was effectively controlled after the operation, body weights increased more than 6kg six months later, and nutrition status, swallowing function and quality of life were all improved. CONCLUSIONS: Intractable post-radiotherapeutic aspiration pneumonia in patients with nasopharyngeal carcinoma was possibly caused by lower cranial nerve palsy, which might be related to radiation fields overlapped. Modified laryngotracheal separation is effective in eliminating intractable aspiration in PNC. Suitable patients should be carefully selected although the procedure is potentially reversible.

Endoscopic sinus surgery for fungal ball rhinosinusitis in South China: long-term results and analysis of prognostic factors.

CONCLUSION: Endoscopic sinus surgery (ESS) treatment has achieved good long-term results in patients in South China with fungal ball rhinosinusitis. Gender (female), age (young), nasal polyps, allergy, high Lund-Mackay scores, prior sinus surgery and diabetes mellitus affect patients' outcomes. OBJECTIVE: To evaluate objective testing and quality of life (QOL) outcomes of patients with fungal ball rhinosinusitis before and after ESS in South China and to determine preoperative factors that predict surgical outcomes. METHODS: We retrospectively analyzed the outcomes for 330 patients with fungal ball rhinosinusitis after ESS. QOL was assessed using Sinonasal Outcome Test-20 (SNOT-20), Short Form-36 (SF-36) questionnaires and visual analogue scale (VAS). Objective testing was evaluated by Lund-Kennedy endoscopic scoring system. Prognostic factors were determined based on the QOL scores and Lund-Kennedy scores after ESS using a multivariate linear regression. RESULTS: ESS significantly improved the objective testing and QOL outcomes in patients with fungal ball rhinosinusitis (p < 0.05). Objective outcome: postoperative Lund-Kennedy scores were significantly worse in patients with nasal polyps, allergy and high Lund-Mackay scores (p < 0.05). QOL outcomes: postoperative SF-36 scores were adversely affected by gender (female), age (young), nasal polyps, allergy and prior sinus surgery (p < 0.05); postoperative VAS scores were adversely affected by gender (female), nasal polyps, allergy and diabetes mellitus (p < 0.05).

Frontal sinus cerebrospinal fluid leaks: repair in 15 patients using an endoscopic surgical approach.

OBJECTIVES: To clarify the utility of a safe and effective endoscopic procedure for closing frontal sinus cerebrospinal fluid (CSF) leaks. METHODS: A retrospective review of all 15 patients seen at our hospital from 2002 to 2008 whose CSF leak originated within the frontal sinus or frontal recess. A transnasal endoscopic or combined transfrontal endoscopic approach was used to repair the CSF leak. RESULTS AND SURGICAL OUTCOMES: Four defects originated in the frontal recess and 11 involved the posterior wall of the frontal sinus. Nine patients were repaired by a direct endoscopic approach and 4 patients were repaired after widening the frontal recess endoscopically. Two patients were repaired using the combined transfrontal and transnasal approach. The leak was stopped in 14 cases (93%) after the first operation. One patient (7%) required a second repair 1 month after initial surgery and has remained well after 27 months. Complications included a frontal lobe abscess and a frontal sinus obstructive mucocele. These 2 patients were successfully treated without further complications. Patient follow-up ranged from 4 to 44 months (mean 30 months). CONCLUSIONS: Most frontal CSF leaks can be successfully closed by an endoscopic surgical approach.

[Clinical study on aggressive rhinocerebral mucormycosis].

OBJECTIVE: To study the clinical diagnosis, course and combined therapy of aggressive rhinocerebral mucormycosis. METHOD: The clinical feature, diagnosis and therapy were analyzed in 5 cases with rhinocerebral mucormycosis throughout disease progress. Good treatments were found by analyzing curative effect of different treatment. RESULT: One patient died within three weeks in hospital three patients survived from 2 months to 2 years; and one patient was alive over 3 years. The mortality rate was 80% in this study. CONCLUSION: Rhinocerebral mucormycosis is always secondary to patients with severe diseases and bad immunologic function. The lesion can invade the orbit and brain quickly, and the mortality rate is high. The cause of the disease can be retarded by clearing up the focus early and removing the environment of fungi thriving with combined therapy. It is effective of remodelling the necrotic tissues by nasal endoscopy.

[Transnasal endoscopic repair of frontal cerebrospinal fluid rhinorrhea].

OBJECTIVE: To explore the surgical approaches, methods and techniques of repair of cerebrospinal fluid (CSF) rhinorrhea via frontal sinus under transnasal endoscopy. METHODS: Cerebrospinal fluid rhinorrhea, located at the posterior wall of the frontal sinus (n = 9) and posterior lateral wall of the frontal recess (n = 4) had been repaired surgically. A transnasal endoscopic approach was chosen in 12 patients and combined approach was used in 1 patient during the first procedure. Three patients needed the second surgery. Among them, one patient needed to repair CSF rhinorrhea, 1 patient needed to treat intracranial abscess of frontal lobe via combined approach and another one was treated because of the complication of frontal cyst. RESULTS: Twelve patients were successfully repaired in the first surgery. Only 1 patient needed second surgery. Two patients occurred complications. One was intracranial infection after surgery, external drainage and packing in the frontal sinus was used. Another was obstructive cyst in frontal sinus, transnasal endoscopic frontal sinusotomy was performed. CONCLUSIONS: CSF rhinorrhea which located at the posterior wall of the frontal sinus can be successfully repaired via transnasal endoscopic approach if the leak was visible under endoscopy. The size of the frontal ostium and leak vantage should be considered to prevent the drainage of the frontal sinus which would result in obstructive cyst in frontal sinus, frontal sinusitis and intracranial infection. Combined approach was suggested to the patients that leakage could not be seen in frontal sinus or frontal ostium was difficult to enlarge.

[Endoscopic evaluation of mucous membrane inflammation in chronic rhinosinusitis and analysis of correlated factors].

OBJECTIVE: The purpose of this article is to establish an endoscopic score system for quantitative evaluation of the inflammation of mucous membrane in patients with chronic rhinosinusitis (CRS) , and to investigate the correlation of this system with a variety of clinical factors. METHODS: A set of score system was constructed based on anatomic configuration, status of mucous membrane and nasal secretion to evaluate quantificationally the severity of inflammation of CRS. The clinical correlation of this system was studied prospectively in 60 CRS patients, with a variety of clinical factors which included age, duration of disease, previous recurrence and the years from recent recurrence, atopy, serum total immunoglobulin E (TIgE), serum eosinophil cationic protein (ECP), the count of blood eosinophil, the count of tissue inflammatory cell, the extension of CRS indicated by CT, smoking, concomitant chronic inflammation in lower respiratory tract. All above factors were analyzed statistically with the endoscopic score by Pearson correlation and multi-factor linear regression analysis. RESULTS: In pearson analysis, the correlative factors with the evaluated score included age (x1, r = - 0.310, P = 0.016), the extension of disease (x2, r = 0. 810, P < 0.0005), recurrence (x3, r = 0.408, P = 0.001), eosinophil of nasal tissue (x4, r = 0.279, P = 0. 031), duration of disease (x5, r = 0.536, P < 0.0005), concurrent nasal polyps (r = 0.549, P < 0.0005), plasm cell (r = 0. 317, P = 0.014) and years from the recent recurrence (r = 0.385, P = 0.002). In multi-factor linear regression, the five independent predictive factors were recurrence, age, extension of disease, tissue eosinophils, years of disease. The regressive equation is y = 10.148 - 0.152 (x1) + 2.250 (x2) + 3.348 (x3) + 1.233 (x4) + 0.270 (x5). CONCLUSIONS: Appropriate score system by nasal endoscopy is feasible to evaluate quantificationally the degree of inflammation of CRS; being appropriately modified, it is even able to reveal the underlying histological behavior finely.