Multiple Allergic Rhinitis Single Nucleotide Polymorphism Variants are Associated with Sleep-Breathing Parameters in Men with Obstructive Sleep Apnea: A Large-Scale Study.

Background: Sleep-disordered breathing is more prevalent in individuals with allergic rhinitis (AR) than in those without AR. In addition to increased risk for sleep-disordered breathing, AR is associated with greater severity of obstructive sleep apnea (OSA) symptoms. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in AR with sleep- and breathing-related parameters in men with OSA. Methods: Men who had complained of snoring were consecutively enrolled in the Shanghai Sleep Health Study of Shanghai Sixth People's Hospital from 2007 to 2018. After rigorous screening, 5322 men were included in the analysis. Anthropometric, fasting biochemical, and polysomnographic parameters, along with 27 AR-associated SNPs were analyzed. The associations between AR-related genetic polymorphisms and OSA were determined via linear, binary, and multinomial logistic regression analyses. Results: Rs12509403 had significantly positive associations with most sleep-breathing parameters. While the risk for OSA was increased by rs12509403, it was decreased by rs7717955 [odds ratio (OR) = 1.341, 95% confidence interval [CI] = 1.039-1.732, P = 0.024; OR = 0.829, 95% CI = 0.715-0.961, P = 0.013, respectively]. A graded increase in the risk of being in the highest quartile (Q4) vs the reference category (Q1) for sleep breathing indicators, especially REM-AHI and NREM-AHI, was identified by rs12509403 (OR = 1.496, 95% CI = 1.175-1.904, P = 0.001; OR = 1.471, 95% CI = 1.151-1.879, P < 0.001, respectively). Conclusion: The association of multiple AR SNPs with OSA-related hypoxia and sleep indices provides a genetic explanation for the higher AR susceptibility of OSA patients. Understanding the AR-related genetic underpinnings of OSA may lead to more personalized treatment approaches.

The Associations of Platelet Activation and Coagulation Parameters with Obstructive Sleep Apnoea: A Large-Scale Observational Study.

Objectives: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease, with alterations in coagulability suspected as the mediating factor. This study explored blood coagulability and breathing-related parameters during sleep in patients with OSA. Design: Cross-sectional observational study. Setting. Shanghai Sixth People's Hospital. Participants. 903 patients diagnosed by standard polysomnography. Main Outcome and Measures. The relationships between coagulation markers and OSA were evaluated using Pearson's correlation, binary logistic regression, and restricted cubic spline (RCS) analyses. Results: The platelet distribution width (PDW) and activated partial thromboplastin time (APTT) decreased significantly with increasing OSA severity (both p < 0.001). PDW was positively associated with the apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), and microarousal index (MAI) (ß = 0.136, p < 0.001; ß = 0.155, p < 0.001; and ß = 0.091, p = 0.008, respectively). APTT was negatively correlated with AHI (ß = -0.128, p < 0.001) and ODI (ß = -0.123, p = 0.001). PDW was negatively correlated with percentage of sleep time with oxygen saturation below 90%(CT90) (ß = -0.092, p = 0.009). The minimum arterial oxygen saturation (SaO2) correlated with PDW (ß = -0.098, p = 0.004), APTT (ß = 0.088, p = 0.013), and prothrombin time (PT) (ß = 0.106, p = 0.0003). ODI was risk factors for PDW abnormalities (odds ratio (OR) = 1.009, p = 0.009) after model adjustment. In the RCS, a nonlinear dose-effect relationship was demonstrated between OSA and the risk of PDW and APTT abnormalities. Conclusion: Our study revealed nonlinear relationships between PDW and APTT, and AHI and ODI, in OSA, with AHI and ODI increasing the risk of an abnormal PDW and thus also the cardiovascular risk. This trial is registered with ChiCTR1900025714.

Multiple genetic variations of chronic rhinosinusitis with nasal polyps are associated with respiratory parameters in men with obstructive sleep apnea.

PURPOSE: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a higher risk of obstructive sleep apnea (OSA). However, the relationship between CRSwNP and OSA remains unclear. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in CRSwNP with sleep- and breath-related parameters in men with OSA. METHODS: We included eight CRSwNP SNPs in 2320 participants after strict screening. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of CRSwNP. A bivariate correlation analysis was used to assess the relationship between CRSwNP genetic polymorphisms and polysomnography parameters in men with OSA. Logistic regression analyses were used to assess the relationship between the risk of OSA and CRSwNP genetic polymorphisms. RESULTS: In moderate OSA, rs28383314 was related to the oxygen desaturation index, and rs4807532 was positively associated with the microarousal index (r = 0.09, P = 0.03 and r = 0.11, P = 0.01, respectively). The CRSwNP GRS was positively correlated with the oxygen desaturation index and cumulative time percentage with SpO2 < 90% in moderate OSA (r = 0.13, P < 0.001 and r = 0.1, P = 0.01, respectively). There was no association between the CRSwNP GRS and the risk of OSA (OR = 1.007; 95% CI, 0.973-1.042; P = 0.702). CONCLUSION: In men with moderate OSA, single CRSwNP genetic variations correlated with sleep-related parameters, and the cumulative effects of CRSwNP genetic variations were associated with the hypoxic index. CRSwNP may be a predisposing condition for sleep disorders in men with moderate OSA.

HMSC-Derived Exosome Inhibited Th2 Cell Differentiation via Regulating miR-146a-5p/SERPINB2 Pathway.

BACKGROUND: Allergic rhinitis (AR) is a global disease without specific treatment. Human mesenchymal stem cell- (HMSC-) derived exosomes (HMSC-exos) have been implicated for the amelioration of allergic inflammation by delivering miR-146a-5p in a mouse asthma model. However, the antiallergic activity and the underlying mechanism of HMSC-exos in AR remain unclear. The present study aimed to investigate the role of HMSC-exos in the pathogenesis of AR. MATERIALS AND METHODS: Blood specimens were collected from AR patients and healthy donators for investigation. HMSC and CD4+ T cells were used in the present study. Flow cytometry was used to characterize the population of Type 1 helper T (Th1) and Th2 cells. Specific siRNA and overexpressed plasmids were designed to silence or overexpress the expressions of miR-146a-5p and SERPINB2. Luciferase reporter assay was adopted to explore the binding site of miR-146a-5p and SERPINB2. Quantitative real-time PCR and immunoblots were performed to estimate the expression of target genes. RESULTS: The population of Th2 cells was significantly elevated in AR patients as compared with that in healthy donators. HMSC-exos could decrease the expression of SERPINB2 and the differentiation of Th2 cells. miR-146a-5p in HMSC-exos exhibited consistent effects and lowered the expression of SERPINB2 by binding on its 3'UTR region. Moreover, the differentiation of Th2 cells was promoted by SERPINB2 that could be reversed by HMSC-exos. Additionally, the miR-146a-5p expression was negatively associated with the SERPINB2 expression in the serum of AR patients. CONCLUSION: HMSC-exos could inhibit the differentiation of Th2 cells via the regulation of the miR-146a-5p/SERPINB2 pathway. miR-146a-5p and SERPINB2 could be applied as potential targets for AR treatment.

Taurine promotes the production of CD4+CD25+FOXP3+ Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model.

BACKGROUND: Allergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa. METHODS: Blood samples from 20 healthy donors and 20 AR patients were compared for CD4+CD25+FoxP3+ T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4+ cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor. RESULTS: Comparison of blood from normal donors and AR patients showed a reduction in CD4+CD25+FoxP3+ Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4+ cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4+ cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4+ cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4+ cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment. CONCLUSIONS: Taurine induces release of IL-35 in AR; IL-35 promotes the production of CD4+CD25+FoxP3+ Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.

In vitro and in vivo Antiallergic Effects of Taurine on Allergic Rhinitis.

BACKGROUND: The current treatment for allergic rhinitis (AR) is inadequate. OBJECTIVE: The present study aimed to investigate the therapeutic effect of taurine on AR and to identify the underlying molecular mechanisms. METHODS: The serum level of the antioxidant enzyme extracellular superoxide dismutase (SOD3) was determined in AR patients and in healthy controls. The antiallergic inflammatory effects of taurine were evaluated in a dinitrophenyl-human serum albumin (DNP-HSA)-stimulated human mast cell line (HMC-1) and in an ovalbumin (OVA)-induced AR mouse model. RESULTS: Clinically, a reduction in serum level of SOD3 was observed in AR patients. Taurine treatment led to dose-dependent increases in SOD3 at both protein and mRNA levels in HMC-1 cells. SOD3 production was regulated by peroxisome proliferator-activated receptor-γ (PPAR-γ) in response to taurine. SOD3 overexpression inhibited the release of proinflammatory cytokines including tumor necrosis factor-α (, interleukin (IL)-4, and IL-6. Its overexpression also ameliorated the loss of interferon-γ. SOD3 and PPAR-γ influenced inflammatory cytokine production via regulation of the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). An OVA-induced AR animal model study showed that taurine was efficacious in alleviating allergic inflammatory reactions by relieving behavior symptoms of AR mice and reducing eosinophilic and mast cell infiltration into the nasal cavity. In addition, taurine treatment increased the production of SOD3 and PPAR-γ, which, in turn, suppressed expression of proinflammatory cytokines through phosphorylation of ERK1/2. CONCLUSION: Taurine could potentially serve as a therapeutic treatment for allergic disorders.

An update on the role of nanovehicles in nose-to-brain drug delivery.

A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, it is difficult for them to outperform conventional formulations, such as solutions or gels. However, nanovehicles bring about special features, such as maintenance of the solubilized state of drugs, sustained or delayed release, and enhanced penetration because of surface modifications, all of which lead to enhanced NTB delivery efficiency.

Evidence of nose-to-brain delivery of nanoemulsions: cargoes but not vehicles.

The nose-to-brain pathway has been proven to be a shortcut for direct drug delivery to the brain. However, whether and to what extent nanoparticles can be delivered through this passage is still awaiting validation with evidence. In this study, nose-to-brain transportation of nanoparticles is tracked via fluorescence bioimaging strategies using nanoemulsions (NEs) as model carriers. Identification of NEs in biological tissues is based on the on → off signal switching of a new type of environment-responsive embedded dyes, P2 and P4, and two conventional probes, DiR and coumarin-6 (C6), are embedded to represent the cargoes. Evidence for the translocation of NEs was collected either via live imaging or ex vivo histological examination in rats after nasal administration. Results suggest that NEs with a particle size of about 100 nm, either naked or coated with chitosan, have longer retention duration in nostrils and slower mucociliary clearance than larger ones. P2 signals, representing integral NEs, can be found in mucosa and trigeminal nerves for all size groups, whereas only weak P2 signals are detected in the olfactory bulb for chitosan-coated NEs of 100 nm. Confocal microscopy further confirms the translocation of integral 100 nm NEs in nasal mucosa and along the trigeminal nerve in decremental intensity. Weak signals of the P4 probe, also representing integral NEs, can be detected in the olfactory bulb but few in the brain. NEs as large as 900 nm cannot be transported to the olfactory bulb. However, the DiR or C6 signals that represent the cargoes can be found in significant amounts along the nose-to-brain pathway and finally reach the brain. Evidence shows that integral NEs can be delivered to the olfactory bulb, but few to the brain, whereas the cargoes can be released and permeated into the brain in greater amounts.

[Effect of nasal instillation of vitamin D3 on patient with allergic rhinitis symptoms].

OBJECTIVE: To investigate the effect of nasal instillation of vitamin D3 on patients with allergic rhinitis symptoms including nasal itching, sneezing, clear nasal discharge, and nasal congestion. METHOD: Thirty subjects with allergic rhinitis proved by skin prick test (SPT) and 30 subjects with deviated septum alone were recrui ted and administrated with 300 000 IU of vitamin D3 by nasal instillation weekly. Seven days after the intervention, the four major symptoms including nasal itching, sneezing, clear nasal discharge, and nasal congestion were evaluated by score. RESULT: After intranasal instillation of vitamin D3, the symptoms in allergic rhinitis group in cluding nasal itching, sneezing, nasal discharge and nasal congestion, and serum 25-hydroxyvitamin D level has statistical differences (P < 0.05). CONCLUSION: Vitamin D3 could be well absorbed through nasal mucosa. It demonstrated to have significantly effect on serum 25-hydroxyvitamin D to improve the symptoms for patients with allergic rhinitis. Vitamin D3 may be a kind of adjuvant therapy for prevention and treatment of allergic rhinitis.

[Preliminary analysis of SPT tests on 5,843 allergic rhinitis patients from south Shanghai area].

OBJECTIVE: To explore the distribution of allergen tested by skin prick test (SPT) in about 5,843 allergic rhinitis patients in south Shanghai. METHOD: SPT test was conducted in 5,843 allergic rhinitis patients who came to our clinic from January 2007 to August 2012. The result was analyzed by age, sex and year. RESULT: The top three allergens by percentage are dermatophagoides pteronyssinus, dermatophagoides culinae and fungus among 15 common allergens. Incidence rate between male and female in each year had statistical significance, both of which showed no increasing trend with year. Incidence rates among different age groups aging from 6 to 17 years' old had no statistically significant difference, but statistically significant difference among different age groups existed in other age groups. Incidence rate showed increasing trend with year in age group of 40-65, which was not observed in other groups. The incidence rate showed decreasing trend with age in male and female, while the incidence rate in male was always higher than female. CONCLUSION: In south Shanghai, primary allergens causing allergic rhinitis are dermatophagoides pteronyssinus, dermatophagoides culinae and fungus. Statistically significant difference about allergic rhinitis existed in age and sex. SPT has important significance in diagnosis of allergens.

[The impact of nasal obstruction on OSAHS].

OBJECTIVE: To evaluate the impact of nasal obstruction on OSAHS. METHOD: One hundred and twenty cases of OSAHS with or without nasal obstruction were analyzed by Hypno PTT(PTT)and Mallampati score (MS); Acoustic rhinometry was measured in all 120 cases. RESULT: A significant correlation was found between the MS and the AHI measured during the sleep (r = 0.266, P < 0.01). The relative risk of OSAHS with a MS of III or IV in the whole group was 1.96, and 2.46 in cases with nasal obstruction. CONCLUSION: A high MS represents a predisposing factor for OSAHS, especially in which associated with nasal obstruction.

[Axillary flap approach to the frontal recess in 20 patients].

OBJECTIVE: To discuss the method and efficacy of Wormald technique application in opening frontal recess surgery. METHOD: Twenty cases with chronic frontal sinusitis underwent surgery with Wormald technique were subjected to this study. Preoperative CT scan and especially sagittal reconstructing were used to indicate the extent of lesion, source and key adjacent structure. RESULT: All patients were followed up for more than half a year with an average of nine months. The effective rate was 90% and no recurrence appeared except for two cases. CONCLUSION: Application of Wormald technique for frontal recess open surgery under endoscope is safe and feasible, with no intracranial, orbital, and other serious complications. All treatments including preoperative sagittal CT, that help to a clear locating the cell lead to the frontal recess obstructive lesions, awarding of the potential difficulties while frontal recess could not be identified, protecting mucous membrane in operation, and strengthening medication, washing, and oxygen spray after operation, can improve operational efficiency.

[Anatomy study of the lacrimal bone in dacryocystorhinostomy].

OBJECTIVE: To explore the significance of the lacrimal bone at the lateral nasal wall in endoscopic dacryocystorhinostomy. METHOD: The position, dimension and thickness of the exposed lacrimal bone at the lateral nasal wall in 10 cadaveric heads(male 5, female 5) were examined and the anatomy of uncinate process, the maxillary line and M point were studied, too. RESULT: The lacrimal bone at the lateral nasal wall is always situated immediately anterior to the uncinate process. The average length and width of the lacrimal bone was 9.23 mm and 3.63 mm, respectively. The lacrimal bone was very thin with an average thickness of 0.06 mm. CONCLUSION: The study indicates that the lacrimal bone is so thin that a bony rongeur is usually sufficient to nibble it away. The medial wall of the sac is then removed without the use of drill or chisel with less operative trauma. The uncinate process, the maxillary line and M point are reliable landmarks in endoscopic dacryocystorhinostomy.

[Comparison of the powered-assisted adenoidectomy with adenoid curette adenoidectomy].

OBJECTIVE: To compare the outcomes of powered-assisted adenoidectomy with adenoid curette adenoidectomy. METHOD: Thirty-four cases with adenoidal hypertrophy were retrospectively analyzed in Shanghai Sixth Peoples Hospital between June 2003 to June 2004. All the patients were followed up six to twelve months. Of 34 cases, 18 children underwent powered-assisted adenoidectomy, and the rest underwent conventional transoral adenoidectomy using a curette. The surgical results were assessed by acoustic rhinometry. RESULT: The averaged time for endoscopic powered-assisted adenoidectomy was 5 minutes and 15 seconds and the time for conventional adenoidectomy was 8 minutes and 22 seconds. There was a significant difference (P < 0.01) between them. The blood loss during powered-assisted and conventional adenoidectomy was 50 (10-125) ml and 75 (5-175) ml respectively, but there was no difference (P > 0.05). One case after powered-assisted adenoidectomy happened bleeding, and one case after conventional adenoidectomy happened dehydration. There were increases in the cross-sectional area at the adenoid, (0.75 +/- 0.58) cm2 preoperatively and (1.94 +/- 0.63) cm2 three months postoperatively, (1.99 +/- 0.44) cm2 one year after operation in powered-assisted group, and (0.80 +/- 0.53) cm2 preoperatively and (1.83 +/- 0.81) cm2 three months postoperatively, (1.89 +/- 0.37) cm2 one year after operation in conventional group. Comparing the preoperative and postoperative cross-sectional area in both groups by acoustic rhinometry, a significant difference (P < 0.01) was found. CONCLUSION: Powered-assisted adenoidectomy has the advantages of shorter surgical time, and less blood loss. Acoustic rhinometry is a kind of objective parameter for assessing the outcome of adenoidectomy.

[Early complications of surgery for chronic suppurative otitis media].

OBJECTIVE: To explore early post-operative complications following surgery for chronic suppurative otitis media. METHOD: From Jan 1992 to July 2000, 291 cases of chronic suppurative otitis media have been treated in our department. 79 cases underwent myringoplasty, 82 cases tympanoplasty, 88 cases modified radical mastoidectomy and 42 cases radical mastoidectomy. RESULT: Facial nerve palsies occurred in 3 cases (1.03%), bone conduction threshold elevation occurred in 13 cases (4.47%), wound infection occurred in 11 cases (3.78%), 7 patients (2.41%) reported symptoms related with chorda tympani trauma, symptoms of jaw discomfort were reported by 7 patients (2.41%) and imbalance or vertigo by 13 patients(4.47%). CONCLUSION: The incidence of early complications of surgery for chronic suppurative otitis media in this report was similar to previous reports.