Study on the relationship between 11β-hydroxysteroid dehydrogenase and glucocorticoid response in nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the expression of 11β-hydroxysteroid dehydrogenase (11β-HSD) in polyps of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and its correlation with glucocorticoid sensitivity.@*Methods@#The prospective study method was applied. Forty-three adult CRSwNP patients from Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University between April 2016 and June 2017 were enrolled in this study. There were 19 males and 24 females with the age of (37.44±7.42) years old. The endoscopic scores by nasal Polyps Grading System before and after one-week prednisone treatment (0.5 mg/(kg·d)) were evaluated. The response of glucocorticoid by the total endoscopic scores was estimated. According to the patient′s reduced nasal polyp endoscopic score, patients were devided into nasal polyps insensitive to glucocorticoids treatment group (insensitive group) and nasal polyp sensitive to glucocorticoids treatment group (sensitive group). The expression of 11β-HSD1, 11β-HSD2 in nasal polyps were measured by Real-time PCR (RT-PCR), Western Blot and immunohistochemisty. According to the clinical data, the Logistic regression models and receiver operation characteristics (ROC) curves were used to explore the predictor for glucocorticoid response in CRSwNP.@*Results@#The expression of 11β-HSD1 and 11β-HSD1/11β-HSD2 was higher in sensitive group than that of insensitive group, while the expression of 11β-HSD2 was lower (rank average was 26.08 vs 16.33, 27.24 vs 14.72, 18.66 vs 26.64, Z value was -2.511, 0.323, -2.059, respectively, all P<0.05). The endoscopic scores in CRSwNP group declined whereas the expression of 11β-HSD1/11β-HSD2 increased (r=0.528, P=0.001), while the cutoff value of the ratio of 11β-HSD1/11β-HSD2 was 2.290 (sensitivity was 79.17%, specificity was 88.89%).@*Conclusions@#There is a positive correlation between the response of glucocorticoid and the ratio of 11β-HSD1/11β-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP.

Clinical features, diagnosis and treatment of silent sinus syndrome / 中华耳鼻咽喉头颈外科杂志

Objective@#To explore the clinical features, diagnostic methods and therapeutic strategy of silent sinus syndrome (SSS).@*Methods@#A retrospective study was made on eight SSS patients treated during 2013-2016 in Longgang ENT Hospital and Otorhinolaryngology Hospital of the First Affiliated Hospital of SUN Yat-sen University. The following clinical data, including demographic data, symptoms, history of trauma and surgery, signs, imaging examination, endoscopic surgery and postoperative outcomes, were analyzed to summarize the diagnosis and treatment experiences.@*Results@#Eight SSS patients showed the following clinical features: the proportions of both sexes and sinus sides were 4 to 4; seven cases (7/8) were adult, with an average of (48.1±11.8)y; seven cases (7/8) had long history of trauma or surgery, with an average of (17.9±10.5)y; seven cases (7/8) cannot recall the exact course of SSS; six cases (6/8) had no nasal symptoms; eight cases (8/8) had unilateral ocular discomforts; eight cases (8/8) had signs of unilateral enophthalmos (2-5 mm), accompanied with hypoglobus; and by CT and MRI scanning, eight cases (8/8) showed the unilateral maxillary sinus outlet obstruction, sinus full opacification, sinus wall bony rarefaction, sinus wall contraction, sinus volume loss, and the ipsilateral orbital floor bowing descent and orbital volume increase. After treated by endoscopic sinus surgery and followed-up for one year, four cases were cured, and the other four improved; no intra- or post-operative complications occurred; and no individual need a two-stage orbital plastic reconstruction.@*Conclusions@#SSS often develops in the unilateral maxillary sinus of adult patient with long history of trauma or surgery, but the nasal symptoms and signs are silent. Diagnostic for SSS depends on characteristic ocular sign and sinus CT imaging. Endoscopic sinus surgery helps to improve ocular and nasal signs and promote orbital self-reconstruction.

Expression of heme oxygenase-1 in nasal polyps and regulation by glucocorticoid / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the expression and possible modulation of heme oxygenase-1 (HO-1) in nasal polyps of patients with chronic rhinosinusitis with nasal polyps (CRSwNP).</p><p><b>METHODS</b>Nasal polyps and uncinate process tissues were collected from 25 CRSwNP patients and 19 healthy controls with nasal septal deviation. HO-1 expression was examined using qRT-PCR, immunohistochemistric staining and Western blot analysis. Moreover, additional uncinate process mucosal samples of 15 healthy controls with nasal septal deviation were harvested for nasal explant culture experiments. HO-1 expression was measured in cultured nasal explant in response to specific inflammatory and glucocorticoid stimulation. SPSS 20.0 software was used to analyze the data.</p><p><b>RESULTS</b>The mRNA and protein expression of HO-1 was significantly increased in polyp tissues, 1.220±0.397 in mRNA and 1.409±0.701 in protein, compared with healthy controls 0.464±0.318 in mRNA and 0.017±0.1147 in protein (U=22.00 in mRNA and U=1.00 in protein, both P< 0.05). The immunohistochemical results showed that HO-1 was mainly distributed in the epithelial layer, submucosal glands and inflammatory cells in nasal tissues. Nasal explant culture experiments demonstrated that HO-1 mRNA was upregulated by IL-17A. The HO-1 mRNA level before the stimulation was 1.000, and 17.264±4.275 after the stimulation of 1 ng/ml IL-17A (U=0, P<0.05), 19.128±4.605 after the stimulation of 10 ng/ml IL-17A (U=0, P<0.05), but was significantly suppressed after stimulation with glucocorticoids (dexamethasone, DEX). The mRNA level after the glucocorticoids stimulation was 0.370±0.101 (U=0, P<0.05) and 0.316±0.167 (U=0, P<0.05) respectively. Furthermore, the HO-1 mRNA was inhibited by TGF-β1, the mRNA level was 0.217±0.322 (U=0, P<0.05), 0.070±0.070 (U=0, P<0.05), respectively.</p><p><b>CONCLUSION</b>Increased HO-1 expression may play a role in the pathogenesis of CRSwNP, which may be considered as the therapeutic target.</p>

A national investigation on the application of Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the application of Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis (2008, Nanchang) on a national scale.</p><p><b>METHODS</b>The contents of the guideline and its relevant applied indicators were designed into an initial questionnaire and, after a pre-survey, revised into a formal questionnaire. Then a stratified sampling was selected out of otolaryngology practitioners in the different level hospitals across the country. After a uniform training, the investigators were sent to these different hospitals to conduct questionnaire survey by face to face interview with otolaryngology respondents. Based on the summarized data, statistical analyses on the awareness and practice status of the guideline, together with their influencing factors, were made. SPSS 16.0 software was used to analyze the data.</p><p><b>RESULTS</b>Issuing and withdrawing questionnaires were performed from December 2012 to June 2013 and 1 240 respondents in 350 hospitals from 30 different provinces, municipalities or autonomous regions were effectively investigated. An average awareness and practice rate of 48.7% and 40.8% upon the guideline was acquired, respectively. There was a significant correlation (r = 0.280, P = 0.000) between the two indicators. With linear regression, county-level hospitals, junior practitioners, non-rhino professionals were the risk factors of poor guideline adherence. In addition, respondents form western region showed lower awareness and practice rate than that of ones from central and eastern region.</p><p><b>CONCLUSION</b>The adherence on Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis is nationally low, so popularization of activities should be urgently strengthened, especially in focus areas, focus hospitals, and focus groups.</p>

Expression and regulation of tight junction protein Occludin in nasal polyps / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the possible role of tight junction protein Occludin in nasal polyps.</p><p><b>METHODS</b>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-β, TGF-α) on the expression of Occludin in cultured human nasal epithelial cells were investigated.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>The reduced expression of Occludin might be involved in the pathogenesis of nasal polyps.</p>

Clinical effect of clarithromycin therapy in patients with chronic rhinosinusitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of clarithromycin (CAM) treatment in adult Chinese patients suffering from chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP).</p><p><b>METHODS</b>A prospective, open and self-controlled clinical trial on patients with CRS was conducted. Fifty patients met inclusion criteria. Of 50 patients, there were 33 patients with CRSsNP and 17 patients with CRSwNP. CAM was administered at 250 mg/d and the duration of administration was 12 weeks. Outcome measures included assessments of visual analogue scale (VAS), the sino-nasal outcome test-20(SNOT-20), the medical outcomes study short-form 36 items(SF-36), Lund-Kennedy endoscopy score, and Lund-Mackay computed tomography score. Before starting the treatment, 2 months after treatment and at the end of treatment, each patient had to complete all the measures except Lund-Mackay computed tomography score, which was only conducted before and after treatment. In order to evaluate the safety of CAM, liver function and renal function in all patients were detected before and after treatment. SPSS 16.0 software was used to analyze the data.</p><p><b>RESULTS</b>Forty-five patients completed 3 months follow-up and 5 patients withdrew due to different reasons. The results were as follows: (1) Thirty-three patients with CRSsNP's VAS scores of four time point were 5.81 ± 1.69, 3.76 ± 1.94, 2.98 ± 1.95, 2.06 ± 2.13, respectively, there were statistically significant improvements in turn (t values were 5.910, 8.090, 8.932, all P < 0.05). Endoscopy score of four time point were 6.28 ± 1.28, 5.00 ± 1.67, 4.12 ± 1.76, 3.12 ± 2.19, respectively, there were statistically significant improvements in turn compared with before treatment (t values were 6.662, 9.161, 9.936, all P < 0.05). The CT scores before and after treatment were 10.33 ± 4.65 and 4.67 ± 4.59, respectively (t = 7.226, P = 0.000) . (2) Seventeen patients with CRSwNP's VAS scores of four time point were 6.07 ± 2.02, 4.87 ± 2.61, 4.06 ± 2.85, 4.08 ± 2.80, respectively, there were statistically significant improvements after 2 or 3 months (t values were 3.285, 3.468, both P < 0.05) except after one month (t = 1.846, P > 0.05). Endoscopy score of four time point were 10.65 ± 1.77, 9.35 ± 1.93, 8.65 ± 2.76, 8.47 ± 2.76, respectively, there were statistically significant improvements in turn(t values were 4.068, 4.863, 5.156, all P < 0.05). The CT scores before and after treatment were 13.82 ± 4.94 and 11.41 ± 5.12, respectively (t = 3.975, P = 0.001). (3) During the period of CAM treatment, 1 patient reported a tolerable headache and weakness and 1 patient had abdominal pain after two months treatment, all the symptoms disappeared while they were asked to stop the drug. Liver function and renal function were detected in 40 patients, the differences before and after treatment were not significant statistically.</p><p><b>CONCLUSIONS</b>Long-term, low-dose CAM treatment is effective in the treatment of CRSsNP and CRSwNP in Chinese patients. Meanwhile, the efficacy of CAM is more significant in polyp-free group compared with polyp group. Low does CAM therapy is safe, and the liver function and renal function does not worsen after 3 months treatment.</p>