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Wang C.,Capital Medical University | Wang C.,Beijing Institute of Otolaryngology | Lou H.,Capital Medical University | Lou H.,Beijing Institute of Otolaryngology | And 9 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background There is little evidence on the efficacy of glucocorticoid transnasal nebulization therapy in patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP). Objective We sought to evaluate the immunologic and remodeling effects of budesonide transnasal nebulization in patients with eosinophilic CRSwNP. Methods Sixty patients with eosinophilic CRSwNP were randomized to receive budesonide or placebo treatment for 14 days by means of transnasal nebulization in a double-blind manner. Endoscopic polyp size scores (maximum = 6 points, Kennedy score) and visual analog scale scores for nasal symptoms were assessed before and after treatment. Similarly, polyp samples were evaluated for inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) by using an immunoassay; collagen by using histochemistry; eosinophils by using hematoxylin and eosin stain; and T-cell subsets by using flow cytometry. Results Budesonide transnasal nebulization significantly reduced polyp size compared with placebo (mean difference between groups,-0.73 units; 95% CI,-1.15 to-0.32 units; P =.002) and improved symptoms. Polyp IL-5 and eotaxin expression decreased significantly, whereas TGF-β and IL-10 expression increased. Expression of IFN-γ and IL-17 was not altered. Budesonide transnasal nebulization consistently reduced eosinophil infiltration and TH2 cell frequency and increased natural regulatory T-cell and type 1 regulatory T-cell frequencies. Indices of remodeling, including albumin, MMP-2, MMP-7, MMP-8, and MMP-9, were significantly decreased, whereas collagen deposition and TIMP-1, TIMP-2, and TIMP-4 levels were significantly increased. Budesonide transnasal nebulization did not suppress the hypothalamic-pituitary-adrenal axis or cause any serious side effects. Conclusion Short-term budesonide transnasal nebulization is an effective and safe treatment option in patients with eosinophilic CRSwNP, achieving clinical improvement by regulating remodeling, cytokine expression, and T-cell subset distribution. © 2014 The Authors.


Bachert C.,Ghent University | Bachert C.,University of Stockholm | Zhang L.,Capital Medical University | Zhang L.,Beijing Institute of Otolaryngology | Gevaert P.,Ghent University
Journal of Allergy and Clinical Immunology | Year: 2015

Chronic rhinosinusitis (CRS) affects more than 10% of the population in the United States and Europe. Recent findings point to a considerable variation of inflammatory subtypes in patients with CRS with nasal polyps and patients with CRS without nasal polyps. According to current guidelines, glucocorticosteroids and antibiotics are the principle pharmacotherapeutic approaches; however, they fail in a group of patients who share common clinical and laboratory markers. Several clinical phenotypes often leading to uncontrolled disease, including adult nasal polyposis, aspirin-exacerbated respiratory disease, and allergic fungal rhinosinusitis, are characterized by a common endotype: a TH2 bias is associated with a higher likelihood of comorbid asthma and recurrence after surgical treatment. As a consequence, several innovative approaches targeting the TH2 bias with humanized mAbs have been subjected to proof-of-concept studies in patients with CRS with nasal polyps with or without comorbid asthma: omalizumab, reslizumab, mepolizumab, and recently dupilumab. Future concepts using upstream targets, such as GATA-3, also focus on this endotype. This current development might result in advantages in the treatment of patients with the most severe CRS. © 2015 American Academy of Allergy, Asthma & Immunology.


Fu Y.,Capital Medical University | Lou H.,Capital Medical University | Wang C.,Capital Medical University | Lou W.,Capital Medical University | And 4 more authors.
Pediatric Allergy and Immunology | Year: 2013

Background: This study aimed to investigate the influence of maternal allergy on cord blood regulatory and effector T cells and to evaluate their role as a predictor of atopic dermatitis (AD) during the first 2 yr of life. Methods: Seventy mother-infant pairs were recruited in this prospective birth cohort study (21 allergic and 49 non-allergic mothers). Cord blood samples were collected and assayed for the percentage of regulatory T cells (Treg), interferon-γ (IFN-γ), and interleukin-4 (IL-4) producing T cells (Th1 and Th2, respectively) using flow cytometry. Experiments were undertaken to assess the function of cord blood CD4+CD25+CD127- Treg cells by cell proliferation and cytokine responses. Their offspring at the age of 2 yr old were evaluated by dermatologists to determine whether they had AD. Results: During the first 2 yr of life, 15.7% of the children developed a physician-diagnosed AD. A significantly increased percentage of Th2 cell was observed in cord blood of newborns with maternal allergy. Treg/Th2 ratio significantly decreased among the offspring of allergic mothers. Treg cell-associated suppression of Th2 response was attenuated in Der p1-stimulated CD4+CD25- T cells from the offspring of allergic mothers. Children with reduced Th1/Th2 (p = 0.001, OR = 0.37) and Treg/Th2 (p = 0.001, OR = 0.47) ratio in cord blood had a higher risk of developing AD. Conclusion: Maternal allergic status is associated with increased percentage of IL-4+CD4+ T cells and a reduced Treg/Th2 ratio in cord blood at their children's birth, which may predispose to an increased risk for developing AD. © 2013 John Wiley & Sons A/S.


Wang M.,Capital Medical University | Wang M.,Beijing Institute of Otolaryngology | Zhang Y.,Capital Medical University | Zhang Y.,Beijing Institute of Otolaryngology | And 4 more authors.
Human Immunology | Year: 2012

Background: Th17 cell lineage, a distinct pro-inflammatory lineage characterized by preferential synthesis of cytokines IL-17A and IL-17F, is thought to play an important role in the pathogenesis of allergic rhinitis (AR). Objectives: Our aim was to investigate whether polymorphisms in and around IL-17A and IL-17F genes are associated with AR and comorbid asthma. Methods: A case-control comparison was performed in a cohort of 279 AR patients, 197 allergic rhinitis with asthma (AR-A) patients and 281 control Chinese subjects, to investigate associations between 19 tagging single-nucleotide polymorphisms (SNPs) in IL-17A and IL-17F gene regions and manifestation of AR or AR-A. Genotyping was performed using the Sequenom MassARRAY platform. Results: SNP rs3819024 in IL-17A gene, intergenic SNPs rs1892280 and rs10807439 were specifically associated with AR protective or risk effects, while rs3819024 in IL-17A gene, intergenic SNP rs13192563 in IL-17F gene were associated with AR-A protective or risk effects. Haplotype analysis showed significant AR risk in haplotype AA (rs1892280G-rs13192563A) and AR protective effect in haplotype GT (rs7758579A-rs11966760T); the haplotype AT(rs7758579-rs11966760) were considered AR-A risk. Conclusions: Our findings preliminarily indicate IL17A and IL17F SNPs, and some intergenic variants have the potential association with AR and comorbid asthma in Chinese population. © 2012 Human Immunology.


Zhao Y.,Capital Medical University | Zhao Y.,Beijing Institute of Otolaryngology | Zhang Y.,Capital Medical University | Zhang Y.,Beijing Institute of Otolaryngology | And 2 more authors.
International Forum of Allergy and Rhinology | Year: 2016

Background: Allergic rhinitis (AR) is a complex chronic inflammatory disease of the nasal mucosa, caused by an interaction between genetic and environmental factors. As evidence suggests that some genetic variants may increase susceptibility to both AR and asthma, the objective of this study was to identify asthma susceptibility variants associated with AR in the Chinese population. Methods: A cohort of 402 individuals with physician-diagnosed AR and 416 healthy controls were recruited from the Han Chinese population in Beijing. DNA was extracted from the peripheral blood and a total of 12 single-nucleotide polymorphisms (SNPs) shown to be associated with asthma in Japanese subjects were selected for genotyping using the SequenomMassARRAY technology platform. Results: Analysis of frequency differences of allele between the AR patients and control subjects showed that the C allele of rs204993 in the pre-B-cell leukemia homeobox 2 (PBX2) gene from the 6p21.3 locus was significantly associated with AR (p = 0.0006, pcorrected = 0.0340). Genotype analysis further confirmed the difference in distribution of this variant between AR patients and controls in the both the dominant (pT/C+C/C vs T/T = 7.37×10-5) and co-dominant (pT/C vs T/T = 1.98 × 10-4, pC/C vs T/T = 0.004) models. Conclusion: These results suggest that the PBX2 gene in the 6p21.3 asthma susceptibility locus may be associated with increased risk for both AR and asthma in Chinese subjects. © 2016 ARS-AAOA, LLC.


Li J.,Capital Medical University | Li J.,Beijing Institute of Otolaryngology | Zhang Y.,Capital Medical University | Zhang Y.,Beijing Institute of Otolaryngology | And 2 more authors.
Current Opinion in Allergy and Clinical Immunology | Year: 2015

Purpose of Review: Allergic rhinitis and allergy are complex conditions, in which both genetic and environmental factors contribute to the pathogenesis. Genome-wide association studies (GWASs) employing common single-nucleotide polymorphisms have accelerated the search for novel and interesting genes, and also confirmed the role of some previously described genes which may be involved in the cause of allergic rhinitis and allergy. The aim of this review is to provide an overview of the genetic basis of allergic rhinitis and the associated allergic phenotypes, with particular focus on GWASs. Recent Findings: The last decade has been marked by the publication of more than 20 GWASs of allergic rhinitis and the associated allergic phenotypes. Allergic diseases and traits have been shown to share a large number of genetic susceptibility loci, of which IL33/IL1RL1, IL-13-RAD50 and C11orf30/LRRC32 appear to be important for more than two allergic phenotypes. GWASs have further reflected the genetic heterogeneity underlying allergic phenotypes. Summary: Large-scale genome-wide association strategies are underway to discover new susceptibility variants for allergic rhinitis and allergic phenotypes. Characterization of the underlying genetics provides us with an insight into the potential targets for future studies and the corresponding interventions. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Wang C.,Capital Medical University | Zhang L.,Capital Medical University | Zhang L.,Beijing Institute of Otolaryngology
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2014

Purpose of review: Allergic rhinitis is a highly prevalent inflammatory disease affecting 20-40% of the children worldwide. Allergen-specific immunotherapy (SIT) is an effective treatment for allergic rhinitis. This article reviews the recent advances in SIT for children. Recent findings: In current clinical practice, immunotherapy is delivered as either subcutaneous immunotherapy or sublingual immunotherapy (SLIT). Most meta-analyses and reviews concluded a trend that subcutaneous immunotherapy was better than SLIT in reducing symptoms of allergic rhinitis and rescue medication use, however, SLIT has a better safety profile than subcutaneous immunotherapy. Additionally, the absence of pain on administration of therapy is a character of SLIT, which is well suited for children. T regulatory cells, especially Tr1 cells that secrete interleukin-10 and induce production of immunoglobulin G4, play a role during SIT. Summary: Although there is substantial evidence for effectiveness of both subcutaneous immunotherapy and SLIT, safer and more effective SIT approaches are needed. New approaches to improve SIT include omalizumab pretreatment, use of recombinant allergens, and alternate routes of administration. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Wang C.,Capital Medical University | Han D.,Capital Medical University | Han D.,Beijing Institute of Otolaryngology | Zhang L.,Capital Medical University | Zhang L.,Beijing Institute of Otolaryngology
ORL | Year: 2012

Objectives: The endoscopic management of inverted papilloma (IP) has gained in popularity over the last 15 years. However, the appropriate management of lesions involving the anterior medial wall of the maxillary sinus still has to be determined. Methods: We performed a retrospective review of the surgical results for patients with IP attached to the anterior medial wall of the maxillary sinus in the Otolaryngology, Head and Neck Surgery Department, Beijing TongRen Hospital. The tumors were removed by using our surgical technique of modified endoscopic maxillary medial sinusotomy, which was defined as an extended endoscopic medial maxillectomy with preservation of the nasolacrimal duct and inferior turbinate. Sinus endoscopy was used to screen for disease after endoscopic resection and the clinical outcomes were analyzed. Results: A total of 7 patients (4 males and 3 females) were identified. Pre-and postoperative pathological examinations revealed inverted papilloma as the diagnosis. All tumors were defined as Krouse III lesions. There were no complications recorded as a result of surgery. All patients remain disease free with a mean follow-up of 35.7 months (range 20-68 months). Conclusion: Sinonasal IP with attachment to the anterior medial portion of the maxillary sinus can be treated successfully using modified endoscopic maxillary medial sinusotomy with preservation of the nasolacrimal duct and inferior turbinate. © 2012 S. Karger AG, Basel.


Han D.,Capital Medical University | Han D.,Beijing Institute of Otolaryngology | Wang C.,Capital Medical University | Lou W.,Capital Medical University | And 4 more authors.
Clinical Immunology | Year: 2010

We investigate the frequencies of CD4+CD25+Foxp3+ T cells and allergen-specific IL-10+IL-4-, IFN-γ+IL-4-, IL-4+IFN-γ-CD4+ T cells (which display characteristics of nTreg, Tr1-, Th1- and Th2- cells, respectively) in peripheral blood mononuclear cells (PBMCs) of patients with AR and of healthy individuals. In addition, we estimated the suppressive effect of CD4+CD25+ Treg cells and allergen-specific, IL-10-secreting cells from both two groups. The frequency of CD4+CD25+Foxp3+ T cells is similar in 43 AR patients compared with 38 healthy subjects. CD4+CD25high cells retain suppressive activity on allergen-stimulated cell proliferation and cytokine production of Th1 but not Th2 cells in both groups. However, the frequency of allergen-specific IL-10+IL-4-CD4+ T cells is reduced in AR patients, and correlates inversely to clinical symptom scores. Allergen-specific, IL-10-secreting cells potently suppressed D. pteronyssinus major allergen 1-stimulated cell proliferation and cytokine production (IFN-γ and IL-4) in healthy individuals. Altogether our data indicate that the number and function of CD4+CD25+ Treg cells from allergic patients are not impaired. However, the deficiency of allergen-specific Tr1 cells may play a role in the development of AR. © 2010 Elsevier Inc.


Jiao J.,Beijing Institute of Otolaryngology | Meng N.,Beijing Institute of Otolaryngology | Zhang L.,Beijing Institute of Otolaryngology
ORL | Year: 2014

Background: The aim of this study was to investigate the effect of the corticosteroids, the antihistamines, and the preservatives benzalkonium chloride (BKC) and potassium sorbate (PS) in intranasal medications on human nasal epithelial ciliary beat frequency (CBF). Methods: Primary ciliated epithelial cell cultures from the human nasal mucosa of chronic sinusitis patients were established. Changes in CBF of epithelial cell cultures treated/untreated with intranasal medications or preservatives were assessed using high-speed digital imaging methods. Results: Budesonide caused a rapid but reversible ciliostasis and showed no ciliotoxic effect at 10% dilution. Fluticasone propionate induced an irreversible ciliostatic activity and showed a reversible decrease in CBF at 10% dilution. Azelastine hydrochloride and levocabastine hydrochloride both induced a dose-dependent and irreversible decrease in CBF, although the ciliotoxic effect was not evident at 5% dilution. BKC resulted in an irreversible ciliostasis at 0.005 or 0.01% concentrations, whereas PS did not show any change in CBF at 0.12 or 0.24% concentrations. Conclusions: Crystalline BKC and BKC-containing intranasal medications, including fluticasone propionate, azelastine hydrochloride and levocabastine hydrochloride, but not PS or PS-containing intranasal budesonide spray, led to irreversible ciliostasis in human nasal epithelial cell cultures when applied at clinically relevant concentrations. © 2014 S. Karger AG, Basel.

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