Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Multimorbidity of Allergic Conditions in Urban Citizens of Southern China: A Real-World Cross-Sectional Study.

BACKGROUND: Extensive knowledge of allergic multimorbidities is required to improve the management of allergic diseases with the industrialization of China. However, the demography and allergen distribution patterns of allergic multimorbidities in China remain unclear, despite the increasing prevalence of allergies. METHODS: This was a real-world, cross-sectional study of 1273 outpatients diagnosed with one or more allergic diseases in Guangzhou, the most populated city of southern China, with leading industrial and commercial centers, between April 2021 and March 2022. Seven allergic diseases (allergic rhinitis (AR), asthma (AS)/cough variant asthma (CVA), atopic dermatitis (AD)/eczema, food allergy (FA), allergic conjunctivitis (AC), drug allergy (DA), and anaphylaxis) were assessed. Positive rates of sensitization to different allergens were measured using an allergen detection system of the UniCAP (Pharmacia Diagnostics, Sweden) instrument platform to compare the groups of allergic multimorbidities against a single entity. RESULTS: There were 659 (51.8%) males and 614 (48.2%) females aged from 4 months to 74 years included in the analysis. The study participants who were diagnosed with allergic diseases had an average of 1.6 diagnoses. Overall, 46.5% (592 of 1273) of the patients had more than one allergic condition, and allergic rhinitis was the most common type of multimorbidity. Women were more likely to suffer from an allergic disease alone, whereas allergic multimorbidities were more likely to be diagnosed in men (p = 0.005). In addition, allergic multimorbidities were common in all age groups, with an incidence ranging from 37.1% to 57.4%, in which children and adolescents were more frequently diagnosed with allergic multimorbidities than adults (18-60 years old) (all p < 0.05). Allergic multimorbidity was observed throughout the year. A difference in the positive rate of allergens sensitization and total immunoglobulin E (tIgE) levels between different allergic multimorbidities was observed. CONCLUSIONS: Allergic multimorbidities were very commonly found in nearly half of all patients with allergies. The proportion of allergic multimorbidities varied with the type of disease, sex, age, and allergen distribution pattern. These findings may help clinicians to develop "One health" strategies for the clinical management of allergic diseases.

A nationwide survey of otolaryngologists' compliance with Chinese guidelines for diagnosis and treatment of allergic rhinitis.

BACKGROUND: A higher compliance with clinical guidelines helps improve treatment outcomes. But the clinical practice of otolaryngologists is not always consistent with guidelines. OBJECTIVE: To describe otolaryngologists' compliance with guidelines about allergic rhinitis (AR) management and identify factors responsible for the discordance between clinical practice and guideline recommendations in China. METHODS: A cross-sectional nationwide survey was designed and conducted via an online platform. Recruitment was done by emailing otolaryngologists registered in the Chinese Society of Otorhinolaryngology-Head and Neck Surgery or by inviting otolaryngologists to scan a Quick Respond (QR) code that linked to the questionnaire at various academic meetings. RESULTS: A total of 2142 otolaryngologists were eligible and completed the survey. Of them, 64.7% had over 10 years work experience and 97.4% had a bachelor's degree or higher. About 18.3% of the participants strictly copied the guideline in clinical practice, while 73.7% used the guideline that had been adjusted according to their clinical experience. Otolaryngologists were most concerned about the efficacy, safety, and minimum age of AR medications, and least concerned about patient preferences. Regarding the use of intranasal steroids (INS), leukotriene receptor antagonists (LTRA), and H1-antihistamines, 86.8%, 55.7% and 51.2% of otolaryngologists complied with the guideline recommendations, respectively. Educational background was a factor affecting the compliance with guidelines and acceptance of INS. CONCLUSION: A vast majority of Chinese otolaryngologists complied with the current Chinese AR guidelines. A difference still existed between the otolaryngologists' real-world and guideline-recommended management. The otolaryngologists should pay more attention to patient preferences. A higher education could improve otolaryngologists' adherence to the guidelines.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

Interleukin-13 Alters Tight Junction Proteins Expression Thereby Compromising Barrier Function and Dampens Rhinovirus Induced Immune Responses in Nasal Epithelium.

Tight junctions (TJs) are intercellular structures which are essential for epithelial barrier function and play an important role in antimicrobial defense. Epithelium dysfunction and type-2-skewed inflammation are two main pathological phenomena of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of pro-inflammatory type-2 cytokine IL-13 on TJs in CRSwNP is poorly understood. Nasal biopsies of CRSwNP patients and in vitro IL-13-matured human nasal epithelial cells (hNECs) were used to analyze epithelial markers and TJ proteins. Epithelium permeability, transepithelial electrical resistance (TEER), expression of TJs were quantified for IL-13-matured hNECs and that with RV infection. The expression of occludin, claudin-3, and ZO-1 were significantly decreased in CRSwNP biopsies and in hNECs after IL-13 treatment. IL-13 treatment increased epithelium permeability, decreased TEER and altered hNECs composition resulting in lesser ciliated cells and mucus over-secretion. Interestingly, claudin-3 is selectively expressed on ciliated cells. While RV infection induced minimal changes to TJs, the IL-13-matured hNECs has reduced capacity for upregulation of IFN-λ1 and CXCL10 but further increased the expression of TSLP upon RV infection. These findings suggested that IL-13-mediated dysfunction of TJs and compromised epithelial barrier. IL-13-induced cilia loss conferred lowered viral replication and impaired antiviral responses of nasal epithelium against RV infection.

Using the internet search data to investigate symptom characteristics of COVID-19: A big data study.

OBJECTIVE: Analyzing the symptom characteristics of Coronavirus Disease 2019(COVID-19) to improve control and prevention. METHODS: Using the Baidu Index Platform (http://index.baidu.com) and the website of Chinese Center for Disease Control and Prevention as data resources to obtain the search volume (SV) of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020 and the epidemic data in Hubei province and the other top 9 impacted provinces in China. Data of 2020 were compared with those of the previous three years. Data of Hubei province were compared with those of the other 9 provinces. The differences and characteristics of the SV of COVID-19-related symptoms, and the correlations between the SV of COVID-19 and the number of newly confirmed/suspected cases were analyzed. The lag effects were discussed. RESULTS: Comparing the SV from January 1, 2020 to February 20, 2020 with those for the same period of the previous three years, Hubei's SV for cough, fever, diarrhea, chest tightness, dyspnea, and other symptoms were significantly increased. The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms (P＜0.001). The SV of COVID-19 in Hubei province was significantly correlated with the number of newly confirmed/suspected cases (r confirmed = 0.723, r suspected = 0.863, both p < 0.001). The results of the distributed lag model suggested that the patients who searched relevant symptoms on the Internet may begin to see doctors in 2-3 days later and be confirmed in 3-4 days later. CONCLUSION: The total SV of lower respiratory symptoms was higher than that of upper respiratory symptoms, and the SV of diarrhea also increased significantly. It warned us to pay attention to not only the symptoms of the lower respiratory tract but also the gastrointestinal symptoms, especially diarrhea in patients with COVID-19. Internet search behavior had a positive correlation with the number of newly confirmed/suspected cases, suggesting that big data has an important role in the early warning of infectious diseases.

Olfactory Sensitivity Is Related to Erectile Function in Adult Males.

BACKGROUND: The olfactory system influences human social behavior, in particular the selection of a spouse. However, there is currently a lack of clinical research on the relationship between the olfactory system and erectile dysfunction (ED) in adult males. AIM: We explored the association between olfactory sensitivity and erectile function and its possible mechanisms. RESULTS: A total of 574 patients, adult males aged between 19 and 42 years, diagnosed with ED in the Department of Infertility and Sexual Medicine of the Third Affiliated Hospital of Sun Yat-sen University from 2015 to 2018 were analyzed retrospectively. Among them, 115 patients (20.03%) had rhinologic diseases (RDs). In addition, in 201 adult male patients who underwent nasal surgery in the ENT department from 2012 to 2016, including 29 (14.43%) with ED, nasal congestion, nasal discharge, and hyposmia were the most common complaints based on the numerical rating scale (NRS). Furthermore, a prospective study was performed in a total of 102 sequential outpatients (male adults) with RD only (n = 46), ED only (n = 42) and both RD and ED (n = 14) in 2019, together with 40 healthy (male adults) volunteers as controls. The results showed that ED patients with RD had severe nasal discomfort and decreased erectile function (P < 0.0001). The olfactory sensitivity of patients with ED was lower than that of the controls, and patients with both ED and RD had the worst olfactory sensitivity (P < 0.0001). Spearman correlation analyses showed that sense of smell was positively correlated with the International Index of Erectile Function-5 score (R = 0.507, P ≤ 0.0001) and the Erection Hardness Scale score (R = 0.341, P < 0.0001). Logistic regression analyses showed that having an olfactory disorder (OD), RD, age, and visual analog scale (VAS, over 5) score were risk factors for ED outcome, indicating that OD patients had a 16.479-fold increased risk for an ED outcome (P < 0.05). CONCLUSION: A significant correlation was detected between olfactory sensitivity and erectile function in adult males. In particularly, impairment of olfactory sensitivity is more common in patients with both ED and RD than in patients suffering from a single disease.

Distribution and Determinants of Dermatophagoides Mites Sensitization ofAllergic Rhinitis and Allergic Asthma in China.

BACKGROUND: The implementation of allergen immunotherapy (AIT) requires extensive knowledge of allergen distribution in the region to identify high-risk regions for AIT utilization. However, the geographical distribution patterns of the major Dermatophagoides allergens in China remain unclear despite the increasing prevalence of these allergens. METHODS: We performed comprehensive database searches of articles demonstrating the distribution patterns of Dermatophagoides-sensitized allergic rhinitis (AR) and allergic asthma (AA) in China, published between 1990 and 2017. RESULTS: We retrieved 163 articles encompassing 114,302 allergen-positive cases to generate the distribution maps. The rate of sensitization to Dermatophagoides pteronyssinus(D. pteronyssinus)and Dermatophagoides farinae (D. farinae) was similar in patients with AR (75.1 vs. 75.2%, p > 0.05) but not in those with AA (78.5 vs. 77.7%, p = 0.041). Patients with AR and AA shared similar regional distribution patterns of both D. pteronyssinus and D. farinae sensitization, which were highest in the southern and central parts of China and lowest in the northern regions, especially in the Northwest. The overall rate of sensitization to D. pteronyssinus and D. farinae was significantly higher in patients with AA (p < 0.001). Additionally, the annual mean temperature and humidity were the 2 major determinants of D. pteronyssinus and D. farinae sensitization in AR and of D. pteronyssinus sensitization in AA, whereas the annual mean temperature was the sole determinant for D. farinae sensitization in AA. CONCLUSION: These findings may inform clinicians of the strategies for the prevention of Dermatophagoides sensitization and may be of benefit to the future clinical management of allergic diseasesassociated with sensitization to Dermatophagoides mites.

Endoscopic anatomical study of the trans-lateral molar approach to the infratemporal fossa.

BACKGROUND: The infratemporal fossa (ITF) is located deep in the skull base. Recently, the endoscopic transoral approach has enabled maxillofacial surgeons to access the ITF using a less invasive approach compared to the traditional transfacial and endonasal endoscopic approaches. OBJECTIVE: The present study aims to provide maxillofacial surgeons with new data concerning direct endoscopic measurement and precise anatomical topography features of the endoscopic trans-lateral molar approach to ITF by comparing the endoscopic and regional anatomy of ITF. A clinical case receiving the proposed surgical approach is used to determine the feasibility of this technique. METHOD: The anatomical data were obtained by measuring the bone anatomical landmarks and analyzing the CT imaging data using GE's Advance Windows 4.1 software on 25 subjects (50 sides). Morphological pictures of the regional anatomy and endoscopic anatomy were obtained from 6 (12 sides) adult cadaver heads, and the anatomical features were described. The present study reports the management of one case using the proposed surgical approach. RESULTS: The proposed surgical approach clearly revealed neurovascular, muscular, and surgical landmarks in the ITF. The surgical case supports the minimally invasive treatment approach, which could rapidly access the ITF and completely excise benign tumors. CONCLUSION: The anatomical studies and surgical case presentation helps us understand the spatial relationship of surgical landmarks of the surgical approach to the ITF for the treatment of benign lesions in the deep cranial base area.

Enhanced recovery after surgery protocols in functional endoscopic sinus surgery for patients with chronic rhinosinusitis with nasal polyps: a randomized clinical trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speed up recovery. This study aimed to assess the impact of ERAS protocols for functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: One hundred and two patients with CRSwNP undergoing FESS were randomly divided into the ERAS group and the control group. The outcomes of the Self-Rating Anxiety Scale (SAS), Visual Analogue Scale (VAS), Medical Outcomes Study Sleep Scale (MOS-SS) and Kolcaba Comfort Scale Questionnaire (GCQ) were determined in both groups. The serum levels of C-reactive protein (CRP) were compared preoperatively and 24 hours postoperatively. RESULTS: The ERAS group had a significantly better SAS scores than did the control group (28 [24, 35] vs. 43 [42, 47], Z = 5.968, P < 0.001). The rhinalgia and headache scores at 2, 24 and 48 hours postoperatively were lower in the ERAS group than that in the control group (all P < 0.001). The outcomes of the MOS-SS (43 [42, 39] vs. 28 [22, 35], Z = 7.071, P < 0.001) and GCQ (76 [68, 87] vs. 64 [50, 75], Z = 4.806, P < 0.001) were significantly different between the two groups. No significant difference was found in the preoperative CRP levels between the two groups (1.3 [0.6, 2.8] vs. 0.5 [0.5, 1.2], Z = 3.049, P > 0.05); However, the CRP level in 24 hours postoperatively was significantly lower in the ERAS group than that in the control group (2.5 [1.4, 3.9] vs. 6.6 [3.8, 9.0], Z = 5.027, P < 0.001). The incidence rates of complications, such as nausea/emesis (χ = 0.343, P > 0.05), hemorrhage, aspiration and tumble, were not increased in the ERAS group compared with those in the control group. The ERAS group had a significantly shorter length of hospital stay (5 [4, 5] days vs. 8 [8,9] days, Z = 8.939, P < 0.001) and hospitalization expenses ($ 2670 [2375, 2740] vs. $3129 [3116, 3456], Z = 8.514, P < 0.001). CONCLUSIONS: ERAS protocols might optimize FESS for patients with CRSwNP by reducing psychological and physical stress, shortening the length of hospital stay and lowering hospitalization expenses without increasing postoperative complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800015791; http://www.chictr.org.cn/showproj.aspx?proj=26872.

Abnormal Spontaneous Neural Activity of the Central Auditory System Changes the Functional Connectivity in the Tinnitus Brain: A Resting-State Functional MRI Study.

OBJECTIVE: An abnormal state of the central auditory system (CAS) likely plays a large role in the occurrence of phantom sound of tinnitus. Various tinnitus studies using resting-state functional MRI (RS-fMRI) have reported aberrant spontaneous brain activity in the non-auditory system and altered functional connectivity between the CAS and non-auditory system. This study aimed to investigate abnormal functional connections between the aberrant spontaneous activity in the CAS and the whole brain in tinnitus patients, compared to healthy controls (HC) using RS-fMRI. MATERIALS AND METHODS: RS-fMRI from 16 right-ear tinnitus patients with normal hearing (TNHs) and 15 HC individuals was collected, and the time series were extracted from different clusters of a CAS template, supplied by the Anatomy Toolbox of the Statistical Parametric Mapping software. These data were used to derive the smoothed mean amplitude of low-frequency fluctuation (smALFF) values and calculate the relationship between such values and the corresponding clinical data. In addition, clusters in the CAS identified by the smALFF maps were set as seed regions for calculating and comparing the brain-wide connectivity between TNH and HC. RESULTS: We identified the different clusters located in the left higher auditory cortex (HAC) and the right inferior colliculus (IC) from the smALFF maps that contained increased (HAC) and decreased (IC) activity when the TNH group was compared to the HC group, respectively. The value of increased smALFF cluster in the HAC was positively correlated with the tinnitus score, but the decreased smALFF cluster in the IC was not correlated with any clinical characters of tinnitus. The TNH group displayed increased connectivity, compared to the HC group, in brain regions that encompassed the left IC, bilateral Heschl gyrus, bilateral supplementary motor area, right insula, bilateral superior temporal gyrus, right middle temporal gyrus, left hippocampus, left amygdala, and right supramarginal gyrus. CONCLUSION: Tinnitus may be linked to abnormal spontaneous activity in the HAC, which can arise from the neural plasticity induced from the increased functional connectivity between the auditory network, cerebellum, and limbic system.

Elevated expression of IL-17RB and ST2 on myeloid dendritic cells is associated with a Th2-skewed eosinophilic inflammation in nasal polyps.

BACKGROUND: Interleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure the expressions of IL-17RB, ST2 and TSLPR, receptor of IL-25, IL-33, and TSLP respectively, on myeloid DCs in nasal polyps (NP) and evaluate their association with local Th2 inflammation and disease severity in patients with NP. METHODS: Samples were collected from 30 NP patients and 16 control subjects recruited prospectively. The mRNA expression of cytokines, including TSLP, IL-25 and IL-33, as well as interferon (IFN)-γ, IL-4, IL-5, IL-13 and IL-17A in NP and control tissues was examined by qualitative polymerase chain reaction (qPCR). The expression of IL-17RB, ST2 and TSLPR as well as other surface markers on myeloid DCs (mDCs) was examined by flow cytometry. RESULTS: Increased numbers of total and activated mDCs were found in NP patients. mDCs demonstrated significantly higher expression of IL-17RB, ST2 and TSLPR than those in control tissues. The activated mDCs exhibited up-regulations of OX40L and ICOSL, but down-regulation of PDL1 in NP. Moreover, the IL-17RB, ST2 and TSLPR levels on mDCs were positively correlated with IL-25, IL-33 and TSLP mRNA levels, respectively, in NP. Furthermore, IL-17RB and ST2 expressions on mDCs were correlated with the IL-5 mRNA level as well as eosinophil number in NP. Importantly, the IL-17RB expression on mDCs and the OX40L expression on activated mDCs in NP were positively correlated with CT score and total nasal symptom score. CONCLUSIONS: Increased expressions of IL-17RB and ST2 on mDCs are associated with enhanced local Th2 inflammation in NP, suggesting that mDCs might play a role in IL-25- and IL-33-induced type 2 responses and eosinophilic inflammation in NP.

A 10-year retrospective study of alterative aeroallergens sensitization spectrum in urban children with allergic rhinitis.

OBJECTIVE: To investigate the alterative spectrum and trends of aeroallergens sensitization in children with allergic rhinitis (AR) in Guangzhou, China in the past 10 years. PARTICIPANTS AND METHODS: In this retrospective study, 4,111 children with complaints of nasal hyper-reactivity who visited the Pediatric Department and/or Otolaryngology Department from January 2007 to November 2016 were enrolled. Serum specific immunoglobulin E was measured and positive detection was made in 3,328 patients, who were, therefore, diagnosed with AR. Positive rates and trends of different aeroallergens sensitization were assessed. The tendency of positive rates changing over the years, and the difference and trends in positive rate of aeroallergen sensitization that occurred in subgroups of gender, age, and season were determined and analyzed with logistic regression. RESULTS: The percentage of detected common aeroallergens in AR children was (from high to low) 81.07%, 34.44%, 14.72%, 11.81%, 6.04%, and 3.70% for house dust mites (HDMs), cat-dog dander, cockroach, mold mixture, tree pollen mixture, and herb pollen mixture, respectively. An ascending trend of aeroallergens sensitization or AR (odds ratio [OR] =1.116, 95% CI: 1.086-1.146) was found. Interestingly, an increasing trend of cat-dog dander and mold sensitization was found in AR children (OR =1.164, 95% CI: 1.133-1.196; OR =1.169, 95% CI: 1.120-1.223) in this retrospective study, while HDMs sensitization held a steady trend (OR =0.983, 95% CI: 0.961-1.007). CONCLUSION: In the increasing trend of aeroallergens sensitization or AR, HDMs sensitization still held the majority. But emphasis should be made on pet allergy for young children with AR in the context of ascending trend of sensitization to cat-dog dander.

Comparative Study of Recessive Spherical Headed Silicone Intubation and Endonasal Dacryocystorhinostomy under Nasal Endoscopy for Nasolacrimal Duct Obstruction.

Between July 2014 and November 2015, we compared the curative effects and cost-effectiveness of two kinds of nasal endoscopic surgery for nasolacrimal duct obstruction (NLDO) in a single-centre, two-armed clinical trial with a 1-year follow-up. We included two groups: a recessive spherical headed silicone intubation (RSHSI) group and an endonasal dacryocystorhinostomy (En-DCR) group; both received nasal endoscopy. Patients were recruited from the Otorhinolaryngology and Ophthalmology departments. The main outcome measures were epiphora improvement (classified as cure, effective, or invalid), cost-effectiveness, visual analogue scale (VAS) intraoperative pain score, bleeding volume, operating time, hospitalisation time, total cost, and VAS postoperative epiphora score. No significant group difference was identified in postoperative epiphora VAS scores (P > 0.050) or success rate (P = 0.406). However, average VAS intraoperative pain score, operating time, bleeding volume, hospitalisation time and total cost in the RSHSI group were clearly lower to those in the En-DCR group (P = 0.000). In conclusion, RSHSI under nasal endoscopy can provide similar treatment outcomes to En-DCR. RSHSI has advantages including minimal invasiveness, reduced risk, shorter duration of surgery and hospitalisation, reduced intraoperative discomfort, and lower financial burden, which is more acceptable to patients. Thus, RSHSI may be the preferred option for NLDO.

The TH2-polarizing function of atopic interleukin 17 receptor B-positive dendritic cells up-regulated by lipopolysaccharide.

BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c+ monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4+ T cells, and cytokine production by these T cells was determined by intracellular flow cytometry. RESULTS: LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86+ mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86+ mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4+ T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4+ T cells to produce higher level of IL-4 but lower level of IFN-γ. CONCLUSION: Atopic IL-17RB+ DCs can be up-regulated by LPS and promote a TH2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease.

CD4(+)T-lymphocyte subsets in nonobese children with obstructive sleep apnea syndrome.

BACKGROUND: To characterize the distribution of both tonsillar and circulating CD4(+)T-lymphocyte subsets, and to explore their clinical relevance in nonobese children with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 53 children who underwent tonsillectomy for either OSAS (n = 25) or primary snoring (PS, n = 28) were prospectively enrolled. Nineteen healthy children without any symptoms were recruited as controls. We quantified the frequencies of CD4(+)T-lymphocyte subpopulations using flow cytometry, serum-related cytokines using enzyme-linked immunosorbent assay, and key transcription factors using quantitative polymerase chain reaction (qPCR). RESULTS: Tonsillar distributions of CD4(+)T-lymphocyte subsets were comparable in the OSAS and PS subjects. The peripheral Th17/Treg ratio was positively correlated to severity as measured by apnea/hypopnea index (AHI), serum C-reactive protein and hypoxia-inducible factor-1α mRNA in the OSAS children (P < 0.05). And AHI was independently associated with the peripheral Th17/Treg ratio (P < 0.05). Furthermore, the response to surgery was associated with a significant reversal of the Th17/Treg imbalance and a concomitant relief of the proinflammatory profile in the OSAS subjects. CONCLUSION: Pediatric OSAS was associated with an altered Th17:Treg balance toward Th17 predominance. The changes in lymphocytic phenotypes that correlated with recurrent intermittent hypoxia in sleep apnea may contribute to the variance in systemic inflammation and downstream morbidities of pediatric OSAS.