Publications by authors named "Chengshuo Wang"

116 Publications

Budesonide repairs decreased barrier integrity of eosinophilic nasal polyp epithelial cells caused by PM.

Clin Transl Allergy 2021 Jul 3;11(5):e12019. Epub 2021 Jul 3.

Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China.

Background: Eosinophilic chronic rhinitis with nasal polyps (eos-CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type-2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type-2 inflammation. Particular matter 2.5 (PM) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM on the barrier function of the eos-CRSwNP epithelium and explored the reparative function of budesonide.

Methods: Samples from noninflammatory nasal mucosa and eos-CRSwNP were collected to establish an in vitro air-liquid interface cultured model. The cells were exposed to PM at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate-labeled 4-kDa dextran, quantitative real-time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme-linked immunosorbent assay or Luminex.

Results: PM increased paracellular flux and downregulated TJ protein expression (zona occuldens-1, occludin, and claudin-1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)-8, IL-10, IL-1, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were significantly increased in the culture medium of cells exposed to PM, and budesonide significantly reduced the changes in IL-8, IL-1, and TIMP-1.

Conclusion: PM impaired the barrier function of eos-CRSwNP epithelial cells and increased the permeability of large molecules. PM also increased the secretion of pro-inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clt2.12029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254582PMC
July 2021

Upregulation of Basonuclin1 Is Associated with p63-Involved Epithelial Barrier Impairment and Type-2 Helper T-cell Inflammation in Chronic Rhinosinusitis with Nasal Polyps.

Int Arch Allergy Immunol 2021 Jun 18:1-12. Epub 2021 Jun 18.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Background: Tumor protein p63 has been shown to be important for epithelial dysfunction, including epithelial barrier defects and mucosal inflammation, in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Basonuclin1 (BNC1), an epithelial-specific transcriptional factor, is a direct downstream target of p63 and thus might be involved in the pathogenesis of CRSwNP.

Objective: We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP.

Methods: Nasal tissue biopsies were obtained from 91 patients to CRSwNP, 49 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 28 control subjects. Immunohistochemistry and immunofluorescence staining were used to determine the distribution of BNC1 in tissues and localization in cells, respectively. Quantitative PCR was performed to detect the expression levels of BNC1, TP63, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes.

Results: BNC1 mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, p = 0.0003) and control groups (2.40-fold, p < 0.0001). BNC1 staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of BNC1 mRNA was strongly correlated with TP63 mRNA level both in tissue biopsies (r = 0.78, p < 0.0001) and epithelial scrapings (r = 0.97, p < 0.0001). BNC1 expression was also positively correlated with epithelial barrier protein genes (CDH1, CLDN1, CLDN4, TJP1, and TJP2) and epithelial genes involved in TH2 inflammation (IL33, CCL26, CLC, and ALOX15).

Conclusions: Overexpression of BNC1 may be associated with increased expression of TP63, and possibly contribute to the epithelial barrier defects and TH2 inflammation in CRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516810DOI Listing
June 2021

Antihistamine premedication improves safety and efficacy of allergen immunotherapy.

Ann Allergy Asthma Immunol 2021 09 27;127(3):363-371.e1. Epub 2021 May 27.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, People's Republic of China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, People's Republic of China; Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, People's Republic of China. Electronic address:

Background: Allergen immunotherapy (AIT)-associated adverse events are a major concern for safety and efficacy of AIT. Presently, there is no consensus to whether antihistamine premedication could improve such conditions.

Objective: To identify the superiority of antihistamine pretreatment in AIT.

Methods: A comprehensive literature search for randomized controlled trials reporting the effects of antihistamine premedication on safety and efficacy of AIT was performed in MEDLINE, Embase, and Cochrane Library databases. Safety was evaluated according to the number of patients reporting systemic adverse reactions (SARs, the primary outcome) and efficacy according to the number of patients achieving target maintenance dose (TMD) and sustained unresponsiveness to allergen.

Results: A total of 11 randomized controlled trials (including 609 patients) satisfied the inclusion criteria for the meta-analysis. All premedication protocols were temporary. Pooled analysis revealed that compared with control patients, significantly fewer antihistamine-pretreated patients reported total and moderate-to-severe SARs (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.23-0.56; P < .05 and OR, 0.20; 95% CI, 0.06-0.74; P < .05, respectively) and total and moderate-to-severe SAR episodes (OR, 0.42; 95% CI, 0.34-0.53; P < .05 and OR, 0.09; 95% CI, 0.01-0.50; P < .05, respectively). Similarly, antihistamine pretreatment significantly increased the number of patients achieving TMD (OR, 2.94; 95% CI, 1.72-5.03; P < .05), but not sustained unresponsiveness (OR, 1.65; 95% CI, 0.77-3.54; P = 0.2), compared with the control group. Subgroup analysis according to different allergens and dose-escalating approaches also displayed superiority of antihistamine pretreatment than control.

Conclusion: Antihistamine premedication can markedly improve safety and efficacy of AIT by reducing frequency and severity of SAR and increasing TMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2021.05.023DOI Listing
September 2021

Naso-ocular neuropeptide interactions in allergic rhinoconjunctivitis, rhinitis, and conjunctivitis.

World Allergy Organ J 2021 May 9;14(5):100540. Epub 2021 May 9.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, 100730, China.

Background: Ocular as well as nasal symptoms contribute to allergic response but remain poorly characterized. The aim of this study was to analyze the levels of substance P (SP), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) in tears and nasal secretions of patients with allergic rhinoconjunctivitis (ARC), allergic rhinitis, and allergic conjunctivitis, while exploring possible mechanisms of naso-ocular interactions.

Methods: A total of 21 patients with ARC, 17 with allergic rhinitis, 13 with allergic conjunctivitis, and 15 healthy controls were enrolled in the study. Nasal secretions and tears were collected. Patient demographics and clinical characteristics were recorded and levels of substance P, VIP, and CGRP were measured.

Results: SP levels in nasal secretions and tears were significantly higher in the ARC, AR, and AC groups. Similar results were obtained for VIP levels. CGRP levels in tears were also significantly higher in the 3 patient groups. The level of SP was significantly higher in the nasal secretions than in the tears of the ARC, AR, and AC patient groups. The level of VIP was significantly higher in the nasal secretions than in the tears in the ARC and AR groups. The level of CGRP was significantly higher in the nasal secretions than in the tears in the ARC and AC groups. Finally, both of the nasal and tear levels of SP and VIP but not CGRP were positively correlated with the visual analog scale (VAS) score in the patients with ARC.

Conclusion: The results of this study suggested that SP, VIP, and CGRP play important roles in the mechanism of ARC and that nasal neurotransmitters and neuropeptides might have more important roles than those of ocular origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.waojou.2021.100540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131918PMC
May 2021

Evaluation of nasal symptoms to distinguish eosinophilic from noneosinophilic nasal polyps based on peripheral blood.

Allergy Asthma Proc 2021 05;42(3):214-221

From the Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) have poorer outcomes after endoscopic sinus surgery and a higher recurrence rate. This study aimed to investigate the profile of clinical symptoms of eCRSwNP and the related risk factors. We prospectively enrolled 298 inpatients with CRSwNP from February 2019 to December 2019. The patients were divided into eCRSwNP and non-eCRSwNP groups based on the percentage of blood eosinophils; the cutoff value was set at 3.05%. Clinical data on questionnaires, visual analog scale (VAS) scores, and laboratory tests were collected. The differences in clinical symptoms, including nasal congestion, rhinorrhea, olfactory disorders, and head and/or facial pain, between the two groups were analyzed to identify the influential factors. Logistic analysis and receiver operating characteristic curves were used to determine the diagnostic benefit for the specific symptom in the patients in the eCRSwNP group. Nasal congestion and olfactory disorders were significantly different between the eCRSwNP and non-eCRSwNP groups. The patients in the eCRSwNP group more frequently had concerns about olfactory disorders (p = 0.002), whereas patients in the non-eCRSwNP group mostly had nasal congestion (p = 0.001). The logistic analysis showed that the primary risk factors for olfactory disorders of eCRSwNP were disease duration (p = 0.014) and alcohol intake (p = 0.012). Olfactory disorders were not associated with the disease course of the eCRSwNP group but were correlated with the disease duration of non-eCRSwNP (p = 0.008). A VAS score for the olfactory disorders of >5.75 could be used to predict the diagnosis of eCRSwNP (area under the curve, 0.674 [95% confidence intervals, 0.559-0.689]; P < 0.001). Olfactory disorder might be the major nasal symptom that could be used to distinguish a peripheral eosinophilia-based definition of eCRSwNP and non-eCRSwNP. The disease duration was a limiting factor for using olfactory to distinguish two subgroups of nasal polyp. The investigation with regard to the accurate time boundary should be further addressed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2500/aap.2021.42.210004DOI Listing
May 2021

Developing nomograms for identifying allergic rhinitis among chronic rhinitis: A real-world study.

World Allergy Organ J 2021 Apr 13;14(4):100534. Epub 2021 Apr 13.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Background: It is difficult to discriminate allergic rhinitis (AR) and nonallergic rhinitis (NAR) in clinical practice due to the similar clinical manifestations. The study was to assess both the demographical and clinical features of AR and NAR in the real-world data of outpatients in China.

Methods: It was a cross-sectional real-world study. AR and NAR were defined based on both subjective symptoms and objective specific serum IgE test. General demographic characteristics as well as clinical information were documented. Patients were further classified according the seasons of initial visiting hospital (during pollen seasons or not). A scoring system presented as nomograms for presence of AR was performed.

Results: In the pollen season group, age distribution, the duration of rhinitis, comorbidity of asthma, food allergies, and score of coughing were found significantly associated with AR. Additionally, in the non-pollen season group, we found that ethnicity, age distributions, duration of rhinitis, comorbidity of asthma, food allergies, and family history of allergy, together with scores of gritty eyes were associated factors of AR. Based on multivariate logistic model, we built two nomograms which included previously identified significant risk factors that could be acquired easily during clinical practice with predictive variables to assess their roles in predicting the risk of AR among outpatients with rhinitis.

Conclusions: The characteristics of patients with different phenotypes of chronic rhinitis are distinctive in different seasons and the developed nomogram in this study might be beneficial for clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.waojou.2021.100534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054181PMC
April 2021

Author Correction: Affinity-coupled CCL22 promotes positive selection in germinal centres.

Nature 2021 Apr;592(7852):E6

Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-021-03384-8DOI Listing
April 2021

Prognostic and pharmacologic value of cystatin SN for chronic rhinosinusitis with nasal polyps.

J Allergy Clin Immunol 2021 Aug 3;148(2):450-460. Epub 2021 Mar 3.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China; Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China; Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Integrated care pathways improve the management of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The application of integrated care pathways requires development of endotype-based biomarkers to stratify patients. The value of cytokines and markers induced by cytokines for the management of CRSwNP is largely unknown.

Objectives: Our aim was to determine the prognostic and pharmacologic value of type 2, non-type 2 cytokines, and markers associated with type 2 inflammation, including CCL26, periostin, and cystatin SN, in nasal secretions for CRSwNP.

Methods: This retrospective study assigned 151 patients with CRSwNP to the discovery and validation phases. Concentrations of cytokines, CCL26, periostin, and cystatin SN in nasal secretions were determined by using Luminex and ELISA. Predictive significance was assessed with receiver-operating characteristic curves. Survival analysis was performed by using Kaplan-Meier curves and Cox regression models.

Results: Cystatin SN was an independent predictor of the uncontrolled status of CRSwNP over a 2-year follow-up after adjustment for other risk factors (hazard ratio = 1.168 and 1.132 in the discovery and validation phases, respectively; both P < .001). Patients with high cystatin SN concentrations presented with a faster onset and higher rate of uncontrolled status than did those with low levels (P < .001). Enhanced medical treatment for patients with high cystatin SN levels postponed the uncontrolled status in the discovery (P = .016) and validation (P = .002) phases but did not completely abolish it by the end of the follow-up.

Conclusion: Cystatin SN levels in nasal secretions hold strong prognostic value and can facilitate medical instructions for managing CRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.01.036DOI Listing
August 2021

Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA-mRNA regulatory networks in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

Int Forum Allergy Rhinol 2021 08 21;11(8):1207-1219. Epub 2021 Feb 21.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.

Background: The precise mechanisms underlying pathogenesis of different subtypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are still unclear. Emerging evidence indicates that microRNAs may play a role in the pathogenesis of CRSwNP. This study aimed to identify the dysregulated microRNA-messenger RNA (miRNA-mRNA) regulatory networks in eosinophilic (E) and non-eosinophilic (non-E) CRSwNP.

Methods: Whole-transcriptome sequencing was performed on nasal tissues of patients with ECRSwNP and non-ECRSwNP, and control subjects. An integrated analysis of miRNA and mRNA expression was conducted to identify key mRNAs and miRNAs involved in the pathogenesis of ECRSwNP and non-ECRSwNP. The miRNAs of interest and their target genes were validated using quantitative real-time polymerase chain reaction (PCR).

Results: A group of differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRs) were identified in ECRSwNP patients vs control subjects, non-ECRSwNP patients vs control subjects, and non-ECRSwNP vs ECRSwNP patients, respectively. Pathway enrichment analysis showed distinct immune and inflammatory functions associated with DE-mRNAs and target genes of DE-miRs in ECRSwNP vs control and non-ECRSwNP vs control groups. The miRNA-mRNA regulatory networks constructed with Cytoscape highlighted the roles of miR-154, miR-221, and miR-223 family miRNAs relating to both ECRSwNP and non-ECRSwNP, and the roles of the let-7 and miR-34/449 families in the development of non-ECRSwNP. Assessment using real-time PCR for the expression of miRNAs and target genes demonstrated highly consistent data with the RNA sequencing data.

Conclusion: ECRSwNP and non-ECRSwNP patients express distinct miRNA-mRNA regulatory networks compared with control subjects, thus providing potential targets for future development of novel therapeutic approaches for the management of CRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22781DOI Listing
August 2021

Affinity-coupled CCL22 promotes positive selection in germinal centres.

Nature 2021 04 17;592(7852):133-137. Epub 2021 Feb 17.

Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.

Antibody affinity maturation depends on positive selection in germinal centres (GCs) of rare B cell clones that acquire higher-affinity B cell receptors via somatic hypermutation, present more antigen to follicular helper T (T) cells and, consequently, receive more contact-dependent T cell help. As these GC B cells and T cells do not maintain long-lasting contacts in the chaotic GC environment, it is unclear how sufficient T cell help is cumulatively focused onto those rare clones. Here we show that, upon stimulation of CD40, GC B cells upregulate the chemokine CCL22 and to a lesser extent CCL17. By engaging the chemokine receptor CCR4 on T cells, CCL22 and CCL17 can attract multiple helper cells from a distance, thus increasing the chance of productive help. During a GC response, B cells that acquire higher antigen-binding affinities express higher levels of CCL22, which in turn 'highlight' these high-affinity GC B cells. Acute increase or blockade of T cells helps to rapidly increase or decrease CCL22 expression by GC B cells, respectively. Therefore, a chemokine-based intercellular reaction circuit links the amount of T cell help that individual B cells have received recently to their subsequent ability to attract more help. When CCL22 and CCL17 are ablated in B cells, GCs form but B cells are not affinity-matured efficiently. When competing with wild-type B cells in the same reaction, B cells lacking CCL22 and CCL17 receive less T cell help to maintain GC participation or develop into bone-marrow plasma cells. By uncovering a chemokine-mediated mechanism that highlights affinity-improved B cells for preferential help from T cells, our study reveals a principle of spatiotemporal orchestration of GC positive selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-021-03239-2DOI Listing
April 2021

Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2-3 Decades.

Int Arch Allergy Immunol 2021 17;182(7):615-624. Epub 2021 Feb 17.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Introduction: Recent studies have shown that inflammatory patterns of nasal polyps from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in East Asia have changed over time. However, to date there is a marked lack of similar data for CRSwNP in Northern China. This study thus aimed to assess the changes in the clinical and histological characteristics of CRSwNP patients from Northern China over the past 2-3 decades.

Methods: This was a retrospective study, which examined data from 2 groups of 150 CRSwNP patients each, who had undergone endoscopic sinus surgery in Beijing Tongren Hospital from 1993 to 1995 (group A) and from 2015 to 2019 (group B). All relevant data for demographic, clinical, and histological parameters were collected for each patient from the 2 groups and compared for overall changes between the 2 groups.

Results: The comorbidity of CRSwNP and asthma increased over time and the cellular phenotype of CRSwNPchanged significantly; in particular, the proportion of eosinophil-dominant CRSwNP increased, lymphocyte-dominant and plasma-dominant CRSwNP decreased significantly, and the proportions of neutrophil-dominant and mixed CRSwNP were not altered. The rate of polyp recurrence increased in CRSwNP but did not in eosinophilic CRSwNP. Smoking and age did not significantly impact the inflammatory patterns of CRSwNP.

Conclusions: The inflammatory patterns of CRSwNP patients have changed and comorbidity of asthma significantly increased in CRSwNP patients in Northern China over the past 2-3 decades.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315665PMC
September 2021

[Antimicrobial peptides and proteins in chronic rhinosinusitis].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Feb;35(2):185-188

The pathogenesis of chronic rhinosinusitis(CRS) is closely related to the interactions between the environmental stimuli and the innate defense system. A vast of defensive molecules, such as antimicrobial peptides and proteins(AMPs) could be secreted by the airway epithelial cells and submucosal glands. As an essential component of innate immune system, AMPs are associated with multiple airway disease, such as CRS, chronic obstructive pulmonary disease, bronchiectasis, allergic asthma and so on. AMPs are expressed vastly in nasal mucosa and could exert fundamental antibacterial and inflamatory regulative functions. However, the pathophysiological mechanism of AMPs in CRS is still unclear. What's more, the heterogeneity among studies is relatively high. Thus, the paper was aimed to review the potential function and inflammatory regulation of AMPs in CRS. More rigorous studies with larger samples are needed in the future, to shed light on its possible pathogeneisis mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13201/j.issn.2096-7993.2021.02.022DOI Listing
February 2021

Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps.

J Immunol Res 2021 7;2021:1057186. Epub 2021 Jan 7.

Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

Introduction: Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP.

Methods: The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further.

Results: The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-1 and IL-4 in cultured nasal tissues , while CLU expression was inhibited by TGF-1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues.

Conclusion: The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/1057186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810533PMC
September 2021

Dynamic Contrast-Enhanced MRI Can Quantitatively Discriminate the Original Site From Peripheral Portion of Sinonasal Inverted Papillomas.

J Magn Reson Imaging 2021 05 26;53(5):1522-1527. Epub 2020 Dec 26.

Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background: Identification of the original site of sinonasal inverted papillomas (SIPs) is difficult but essential for reducing the recurrence rate. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide information about tissue perfusion and permeability to solve this problem.

Purpose: To investigate the accuracy of DCE-MRI parameters in discriminating between regions of interest (ROIs) in the original site and peripheral portion.

Study Type: Retrospective.

Population: Ninety consecutive patients with pathologically proven SIP.

Field Strength/sequence: 3.0T/DCE-MRI using fast-spoiled gradient recalled (FSPGR) T -weighted images with fat saturation.

Assessment: ROIs were placed in the original site and the peripheral portion of SIP by two radiologists according to surgical records. Maximum slope of increase (MaxSlope), contrast-enhancement ratio (CER), bolus arrival time (BAT), initial area under the signal intensity-time curve (IAUGC), volume transfer constant (K ), volume of the extravascular extracellular space (v ), and rate constant (K ) were calculated and repeated again with a month interval by a radiologist.

Statistical Tests: Univariate and multivariate analysis was used to determine the best diagnostic parameters, and their performances in discrimination were evaluated by receiver operating characteristic (ROC) curves. Reproducibility was estimated by the intraclass correlation coefficient (ICC).

Results: MaxSlope, CER, IAUGC, K , and v were significantly lower (P < 0.05) in the original site than the peripheral portion of SIPs. CER (odds ratio [OR] = 0.227, 95% confidence interval [95% CI] = 0.073-0.704) and v (OR = 0.048, 95% CI = 0.004-0.527) were the best indicators for identifying the original ROIs. The combination of CER and v had the best diagnostic performance in the discrimination between the ROIs (the area under the curve [AUC]: 0.937; 95% CI: 0.896-0.974).

Data Conclusion: DCE-MRI derived parameter values differed between the original site and the peripheral portion of SIPs. The model combining CER and v appears to be able to accurately distinguish the original from peripheral ROIs.

Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27474DOI Listing
May 2021

Blood eosinophil count combined with asthma history could predict chronic rhinosinusitis with nasal polyp recurrence.

Acta Otolaryngol 2021 Mar 10;141(3):279-285. Epub 2020 Dec 10.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Background: The use of non-invasive clinical markers for predicting CRS recurrence is still not well investigated.

Objective: The aim of this study was to investigate the comprehensive effects of non-invasive clinical markers on the recurrence of CRS with nasal polyps (CRSwNP).

Materials And Methods: A total of 346 consecutive CRSwNP patients undergoing endoscopic functional sinus surgery were recruited. The demographic characteristics and clinical parameters were recorded. Machine learning algorithm were used for evaluating the predictive value of asthma history and blood eosinophils percentage.

Results: Finally, 313/346 patients completed the study. The average follow-up time was 24 months after the first surgery. For the CRSwNP with asthma patients, the blood eosinophils percentage cut-off value was 3.7%. However, for the CRSwNP without asthma patients, the blood eosinophils percentage cut-off value was high, at 6.9%.

Conclusion: Combined asthma history and blood eosinophils percentage can predict CRSwNP recurrence, while asthma history can reduce the threshold of blood eosinophils percentage to predict CRSwNP recurrence.

Significance: For the CRS patients, combined asthma history and blood eosinophils percentage can predict recurrence, while asthma history can reduce the threshold of blood eosinophils percentage to predict recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00016489.2020.1844288DOI Listing
March 2021

The 15° reverse Trendelenburg position can improve visualization without impacting cerebral oxygenation in endoscopic sinus surgery-A prospective, randomized study.

Int Forum Allergy Rhinol 2021 06 7;11(6):993-1000. Epub 2020 Dec 7.

Department of Otolaryngology-Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Background: In this study we compared intraoperative bleeding and regional cerebral oxygenation in patients with different degrees of the reverse Trendelenburg position (RTP) during endoscopic sinus surgery (ESS).

Methods: In total, 120 patients with chronic rhinosinusitis treated by ESS were randomly assigned to the following 4 groups: a horizontal position (HP) group, and 5°, 10°, and 15° RTP (5-RTP, 10-RTP, and 15-RTP, respectively) groups. The primary outcome was the Boezaart grading scale (BS). The cerebral oxygen saturation (ScO ), total blood loss, numerical rating scale (NRS) scores, and complications were also recorded.

Results: The median BS values in the HP, 5-RTP, 10-RTP, and 15-RTP groups were 2.0, 2.0, 2.1, and 1.7, respectively. Multiple pairwise comparisons of the BS showed significant differences between the 15-RTP group and the other 3 groups (HP, 5-RTP, and 10-RTP). Regarding the NRS and bleeding rate, significant differences were found between the HP and 15-RTP groups. No difference was found in ScO among the 4 groups, and no cerebral desaturation events occurred in any group. No complications, including vital organ (heart, brain, and kidney) dysfunction problems, were reported in this study during hospitalization.

Conclusion: Compared with HP, 5-RTP, and 10-RTP, 15-RTP can improve visual clarity during ESS, and ScO is not affected by the degree of RTP. No cerebral deoxygenation or vital organ dysfunction was observed in this study. Therefore, we recommend 15-RTP with moderate deliberate hypotension for ESS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22734DOI Listing
June 2021

Diagnosis and treatment of non-allergic rhinitis: focus on immunologic mechanisms.

Expert Rev Clin Immunol 2021 01 17;17(1):51-62. Epub 2020 Dec 17.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing China.

Introduction: Non-allergic rhinitis (NAR) is a heterogeneous nasal disease with high global prevalence. NAR can be subclassified as nonallergic rhinitis with eosinophilia syndrome (NARES), vasomotor rhinitis (VMR), and local allergic rhinitis (LAR). Although the precise factors involved in the etiology of NAR are not clear, there is evidence that immunological factors play an important role in the pathogenesis of NAR. This review provides a comprehensive overview of the immunological and neurogenic mechanisms involved in the diagnosis and treatment of NAR.

Areas Covered: This review provides a comprehensive overview of the immunological basis of diagnostic and treatment strategies for NARES, VMR, and LAR. In particular, recently documented molecular and immunological mechanisms of NAR are discussed, which may help to better understand the mechanisms underlying the pathologies of the different endotypes of NAR.

Expert Opinion: An increasing number of studies investigating the pathogenesis of NAR suggest that the immunological mechanisms underlying the different subtypes of NAR vary greatly, and are still not fully understood to accurately diagnose these subtypes. Thus, further studies should focus on making diagnosis and treatment of NAR more precise, safe, and effective. A better understanding of the immunological mechanisms involved in NAR should help in the discovery of new diagnostic and treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1744666X.2020.1858804DOI Listing
January 2021

Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps.

Allergy 2021 03 29;76(3):789-803. Epub 2020 Nov 29.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS-CoV-2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS-CoV-2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP.

Methods: The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated.

Results: ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected.

Conclusion: These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753806PMC
March 2021

Inflammatory endotypes of CRSwNP and responses to COVID-19.

Curr Opin Allergy Clin Immunol 2021 02;21(1):8-15

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University.

Purpose Of Review: Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly become a great public health hazard globally. Nasal epithelial cells are an important site for SARS-CoV-2 infection and replication. The purpose of this review is to summarize recent findings on the endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) and the potential impact of SARS-CoV-2 infection.

Recent Findings: Endotypes of CRSwNP are characterized by type 1, type 2 and type 3 inflammation according to patterns of inflammatory cells and the cytokines expressed in nasal tissue. Nasal epithelial cells show the highest expression of angiotensin-converting enzyme 2 (ACE2), the receptor for attachment and entry of SARS-CoV-2 into host cells, among all investigated cells in the respiratory tree. SARS-CoV-2 infection likely leads to increased activation of T-helper-1 (Th1) cell responses. Recent studies further suggest that ACE2 may be upregulated by type 1 and downregulated by type 2 inflammatory cytokines in nasal epithelial cells.

Summary: Expression of ACE2 in nasal epithelial cells is influenced by inflammatory endotypes of CRSwNP. Type 1 inflammation in nasal tissue may increase the risk of SARS-CoV-2 infection by upregulating ACE2 expression. However, clinical association between CRSwNP and COVID-19 is still unclear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACI.0000000000000700DOI Listing
February 2021

Predictive significance of arachidonate 15-lipoxygenase for eosinophilic chronic rhinosinusitis with nasal polyps.

Allergy Asthma Clin Immunol 2020 16;16:82. Epub 2020 Sep 16.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, 100730 People's Republic of China.

Background: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) exhibits a poorer outcome compared with non-eosinophilic chronic rhinosinusitis with nasal polyps (nonECRSwNP), so it is significant to identify effective markers to differentiate ECRSwNP in guiding the treatment strategies of these patients. Although arachidonate 15-lipoxygenase (ALOX15) is positioned as a marker of eosinophilic inflammation, its study in differentiating ECRSwNP has not been reported. The aim of this study is to assess the potential of ALOX15 in distinguishing and predicting ECRSwNP.

Methods: Forty-eight patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including 30 ECRSwNP and 18 nonECRSwNP patients, were enrolled. ALOX15 mRNA level was determined in polyps by real-time polymerase chain reaction (RT-PCR). The patients' baseline characteristics were evaluated and analyzed for correlations with ALOX15. Receiver operating characteristic (ROC) curve was used to assess the predictive significance of the potential predictors for ECRSwNP.

Results: ALOX15 mRNA level was significantly higher in ECRSwNP patients than in nonECRSwNP patients ( < 0.001). ALOX15 mRNA was significantly correlated with tissue and blood eosinophil percentages ( = 0.565,  < 0.001 and  = 0.395,  = 0.006), olfaction scores ( = 0.400,  = 0.005), total visual analogue scale (VAS) symptom scores ( = 0.383,  = 0.007), ethmoid/maxillary sinus (E/M) ratio ( = 0.463,  = 0.001), and endoscopy scores ( = 0.409,  = 0.004). Logistic regression analysis showed ALOX15 mRNA level and percentage of blood eosinophils to be predictive factors for ECRSwNP ( = 0.004 and  = 0.036, respectively). ROC curve indicated ALOX15 to have high predictive accuracy for ECRSwNP (area under the curve (AUC) = 0.909), which was further improved by combination of ALOX15 with percentage of blood eosinophils (AUC = 0.933).

Conclusions: The relative ALOX15 mRNA level alone or in combination with blood eosinophils might be a reliable biomarker for predicting a diagnosis of ECRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13223-020-00480-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493848PMC
September 2020

sublingual immunotherapy for seasonal allergic rhinitis: A multicenter, randomized trial.

World Allergy Organ J 2020 Sep 8;13(9):100458. Epub 2020 Sep 8.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, 100730, China.

Background: is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for -induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for -related AR.

Methods: This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 -sensitized eligible patients were randomized in a ratio of 2:1 to receive -SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced.

Results: Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 ± 0.47 vs 1.88 ± 0.42, P < 0.0001 in full analysis set [FAS]; 1.49 ± 0.52 vs 1.95 ± 0.46, P < 0.0001 in per protocol set [PPS]); representing a 22.3% and 23.6% reduction, respectively, relative to placebo. In specifically monosensitized patients, mean daily CSMRS reductions were demonstrated as 24.1% and 27.0% in the FAS and PPS populations, respectively, when comparing the active treatment to placebo treatment. Similarly, SLIT decreased dTNSS in peak pollen period by 19.0% in FAS and 22.3% in PPS, respectively, relative to placebo. In coincidence, dRMS in peak pollen period was reduced by 22.0% in FAS and 26.0% in PPS. 65.8% patients in SLIT group experienced treatment-related AEs, none of which was serious.

Conclusion: This study indicates that SLIT with drops is an effective and safe treatment option in Chinese patients with -induced AR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.waojou.2020.100458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490724PMC
September 2020

Predictive Significance of Charcot-Leyden Crystal Protein in Nasal Secretions in Recurrent Chronic Rhinosinusitis with Nasal Polyps.

Int Arch Allergy Immunol 2021 14;182(1):65-75. Epub 2020 Sep 14.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Introduction: The recurrence occurs frequently among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and predictors that could be conveniently detected during practice in outpatient service are needed.

Objective: We aimed to illustrate that the concentration of Charcot-Leyden crystal (CLC) in nasal secretions can effectively and noninvasively predict polyp recurrence.

Methods: 108 patients with CRSwNP were divided into recurrence (n = 68) and recurrence-free (n = 40) groups. Preoperative CLC concentrations in nasal secretions were collected and detected by ELISA. Polyp tissues were harvested during biopsy or endoscopic sinus surgery and were evaluated for inflammatory cells by histopathological staining. Demographic information and the clinical characteristics of each patient were reviewed for associations with recurrence. Binary logistic regression analysis was performed to determine predictive factors for polyp recurrence. Receiver operating characteristic (ROC) curves and the Youden index were performed to determine their predictive values. Survival analysis was performed to compare recurrence risk of patients with different CLC concentrations.

Results: Sixty-eight (62.96%) patients developed recurrence during a 12- to 33-month postoperative follow-up. CLC concentrations in nasal secretions were positively correlated with eosinophil percent in polyp tissue and peripheral blood and were significantly higher in patients of the recurrence group than in the patients of the recurrence-free group (p < 0.001). Binary logistic regression and ROC curve demonstrated that CLC protein in nasal secretions is predictive of polyp recurrence. According to the Youden index, a CLC concentration of 34.24 ng/mL can predict postoperative polyp recurrence with 92.6% sensitivity and 87.5% specificity. Patients with CLC concentrations higher than the cutoff value yielded a higher risk of recurrence (p < 0.001, HR = 11.31, 95% CI: 6.41-19.98).

Conclusions: CLC protein in nasal secretions may serve as a promising noninvasive biomarker to predict CRSwNP recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510120DOI Listing
August 2021

Advances and novel developments in allergic rhinitis.

Allergy 2020 12 22;75(12):3069-3076. Epub 2020 Sep 22.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Allergic rhinitis (AR) is an upper airway disease with high prevalence in the world, and therefore needs to be thoroughly investigated and treated accordingly. Although the mechanisms underlying the pathology and treatment of AR have been widely studied, many aspects of AR are still unclear and warrant further investigations. The purpose of the present review was therefore to report recently published papers, which highlight the novel mechanisms and treatments of AR. These include role of environment, important proteins and cells, and some other factors in the pathogenesis of AR; as well as the role of immunotherapy and biologics in the treatment of AR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14586DOI Listing
December 2020

[Study on the diagnosis of idiopathic rhinitis by cold dry air provocation].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Aug;34(8):673-677

Department of Otolaryngology Head and Neck Surgery,Beijing TongRen Hospital,Capital Medical University,Beijing,100730,China.

This study aimed to compare the nasal response of cold dry air(CDA) provocation in patients with idiopathic rhinitis(IR) and healthy individuals, and further assess its ability in diagnosing IR. CDA provocation was performed among 15 healthy volunteers and 17 IR patients from Beijing Tongren Hospital Outpatient Department. Nasal symptom scores, total nasal volume(TNV), total nasal resistance(TNR) and minimal cross-sectional area(MCA) were checked before and after the provocation. Logistic regression analysis and Receiver Operating Characteristic(ROC) curves were used in data evaluation. Subjects in the IR group showed significantly larger changes after CDA provocation in total nasal symptom score(TNSS), total nasal resistance(TNR), minimal cross-sectional area(MCA) and total nasal volume(TNV), compared with healthy volunteers. We built a predictive model for IR, Y=0.394×ΔTNSS-0.061 ×ΔTNV(%)+0.014×ΔTNV(%) -2.318, whose area under curve was 0.919 based on multi-factor logistic regression and ROC curve. According to the Youden index, the cut-off criteria was set to be Y >0.49, when its sensitivity and specificity were 82.4% and 84.6%, respectively. Aggravated nasal symptoms and decreased nasal ventilation could be seen after CDA provocation in the IR population. The CDA provocation provides a possible method for assisting the diagnosis of IR, and we'll expand the sample size in future research to verify its clinical application value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13201/j.issn.2096-7993.2020.08.001DOI Listing
August 2020

Self-reported course of olfactory impairment determines outcome for successful surgical intervention in nasal polyps with anosmia.

Acta Otolaryngol 2020 Dec 18;140(12):1021-1027. Epub 2020 Aug 18.

Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.

Background: Olfactory impairment is one of important symptoms of Chronic rhinosinusitis with nasal polyps (CRSwNP). However, the relationship between course of olfactory impairment and postoperative symptom improvement was still unclear.

Objective: The aim of this study was to assess the relationship between the self-reported course of olfactory loss and the degree of improvement in olfaction to determine the timing for successful surgical intervention in improving olfaction in patients with CRSwNP.

Materials And Methods: A total of 86 CRSwNP patients with loss of smell and undergoing functional endoscopic sinus surgery (FESS) were recruited consecutively. The self-reported course of smell lose before treatment was recorded. Olfactory function was recorded before and after FESS using T&T Olfactometry.

Results: Fifty-seven patients demonstrated recovery of olfaction and 29 patients no-recovery. The average recovery time of smell loss in the study was 2.6 weeks. The course of smell loss showed moderate accuracy as a marker for determining the timing for successful FESS; with up to 4.5 years of self-reported smell loss being the cut-off point for recovery of smell following FESS.

Conclusion: This study suggests that FESS in CRSwNP patients with self-reported significant olfactory impairment for less than 4.5 years may lead to improvement in olfaction.

Significance: FESS in CRSwNP patients with self-reported significant olfactory impairment persisting for less than 4.5 years may lead to considerable improvement in olfaction in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00016489.2020.1805508DOI Listing
December 2020

Charcot-Leyden Crystal Protein in Nasal Secretions of Patients with Nonallergic Rhinitis with Eosinophilia Syndrome.

Int Arch Allergy Immunol 2020 21;181(11):888-896. Epub 2020 Jul 21.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China,

Introduction: Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation.

Objective: The purpose of this study was to investigate the role and levels of CLC protein in patients with nonallergic rhinitis with eosinophilia syndrome (NARES).

Methods: Overall, 39 NARES patients and 19 controls were recruited. The severity of nasal symptoms was measured by visual analogue scale and serum and local specific immunoglobulin E were determined in all patients. Nasal eosinophilia was assessed by semiquantitative analysis of eosinophils in nasal scrapings. Nasal secretion CLC protein concentrations were evaluated by ELISA.

Results: CLC protein concentrations were significantly higher in NARES patients than in controls (p < 0.0001). Nasal secretion CLC protein levels were significantly correlated with the degree of eosinophilia in nasal scrapings (rs = 0.331; p = 0.04) in NARES patients. Patients with high CLC protein concentrations displayed more severe nasal symptoms than patients with low CLC protein concentrations (p = 0.0080), particularly, nasal itching (p = 0.0029). Pilot study in 8 NARES patients demonstrated that treatment for 1 month with intranasal fluticasone propionate significantly decreased the nasal secretion CLC protein concentrations from baseline levels (p = 0.0335) and markedly attenuated the degree of swelling of inferior turbinate.

Conclusions: CLC protein levels are significantly higher in nasal secretions of NARES patients and associated with the degree of nasal eosinophilia and the severity of nasal symptoms. Significantly, nasal secretion CLC protein levels obviously decreased after treatment with intranasal corticosteroids, suggesting its possible role in evaluating the medical treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509252DOI Listing
January 2021

Prognostic Factors of Sinonasal Squamous Cell Carcinomas Arising De Novo and From Inverted Papilloma.

Am J Rhinol Allergy 2021 Jan 12;35(1):114-121. Epub 2020 Jul 12.

Department of Otolaryngology Head and Neck Surgery, 117902Beijing Tongren Hospital, Capital Medical University, Beijing, PR China.

Background: The prognostic factors and survival difference between inverted papilloma (IP)-associated sinonasal squamous cell carcinoma (SCC) and de novo SCC are unclear.

Objective: This study aimed to compare the clinical features and oncologic outcomes in patients with IP-associated SCC and de novo SCC; and additionally, to analyze the prognostic factors of the two types of SCCs.

Methods: Data from 173 SCC patients treated for IP-associated SCC (n = 89) and de novo SCC (n = 84), were reviewed retrospectively for demographic features, tumor characteristics, treatment modality, and clinical outcomes. 5-year overall survival (OS) and disease free survival (DFS) was analyzed using the Kaplan-Meier method, and Cox proportional hazards model was used to analyze factors influencing prognosis.

Results: A higher proportion of IP-associated SCC occurred in frontal and sphenoid sinus compared to de novo SCC. The two groups demonstrated similar 5-year OS and DFS (5-year OS: 63.3% and 55.4%, DFS: 45.4% and 50.1%, respectively). The metachronous tumor had a relatively better prognosis outcome than synchronous tumor and de novo SCC (5-year OS: 73.1%, 54.5% and 55.4%, respectively). Both groups showed similar loco-regional recurrence rates ( > 0.05); however, de novo SCC tumors demonstrated an increased incidence of distant metastasis. Multivariate analysis indicated that age >70 years, advanced tumor stage and surgical margin were independent predictive factors for the risk of mortality (HR 2.047, 1.581 and 1.931, respectively).

Conclusion: IP-associated SCCs have an aggressive loco-regional tendency, whereas de novo SCCs have a higher aggressive distant metastatic propensity. Age, tumor stage and surgical positive margin are key factors for poor prognosis and should be routinely taken into consideration during treatment planning and subsequent surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1945892420939422DOI Listing
January 2021

Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma.

Clin Transl Allergy 2020 3;10:26. Epub 2020 Jul 3.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, No. 1, DongJiaoMinXiang, DongCheng District, Beijing, 100730 China.

Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP + AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP + AS.

Methods: A total of 195 subjects; including 65 CRSwNP + AS patients, 99 CRSwNP-alone patients, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP + AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated.

Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP + AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP + AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP + AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP + AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP + AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP + AS.

Conclusions: Patients with CRSwNP + AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13601-020-00332-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333405PMC
July 2020

Diagnosis and management of nonallergic rhinitis with eosinophilia syndrome using cystatin SN together with symptoms.

World Allergy Organ J 2020 Jul 17;13(7):100134. Epub 2020 Jun 17.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, 100730, China.

Background: The diagnosis and treatment of nonallergic rhinitis with eosinophilia syndrome (NARES) remain controversial. The aim of this study was to evaluate whether Cystatin SN together with symptoms can be used to diagnose NARES and to measure the efficiency of medical treatment.

Methods: Seventy-five patients with chronic rhinitis (CR) and 18 control subjects were enrolled. Their clinical characteristics were reviewed and laboratory parameters were evaluated. The concentration of Cystatin SN in nasal secretions was determined using the enzyme-linked immunosorbent assay. The histological assessment of Cystatin SN in the nasal mucosa was conducted by hematoxylin and eosin staining. The logistic regression and receiver operating characteristic curves were used to assess the predictive value of parameters for NARES.

Results: Nasal obstruction, sneezing, loss of smell, and total visual analogue scale (VAS) score were significantly different among the patients with CR. In particular, olfaction score was higher in patients with NARES than in those without NARES (AR, LAR, or IR). Similarly, the Cystatin SN level was significantly different between the control subjects and patients with CR. After treatment for 2 weeks, the Cystatin SN level and VAS score were significantly decreased in the NARES group. The accuracy of Cystatin SN together with local sIgE and loss of smell to diagnose NARES was up to 0.987 (sensitivity, 100%; specificity, 93.1%).

Conclusions: Cystatin SN with local sIgE and loss of smell may serve as one of the reliable and alternative biomarkers for the diagnosis of NARES and be used to evaluate disease severity and NARES treatment efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.waojou.2020.100134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301177PMC
July 2020

Chronic invasive fungal rhinosinusitis vs sinonasal squamous cell carcinoma: the differentiating value of MRI.

Eur Radiol 2020 Aug 11;30(8):4466-4474. Epub 2020 Apr 11.

Department of Radiology, Beijing Tongren Hospital, Capital Medical University, No. 1, DongJiaoMinXiang Street, DongCheng District, Beijing, 100730, China.

Objectives: To investigate MRI features in discriminating chronic invasive fungal rhinosinusitis (CIFRS) from sinonasal squamous cell carcinomas (SNSCC).

Methods: MRI findings of 33 patients with CIFRS and 47 patients with SNSCC were retrospectively reviewed and compared. Multivariate logistic regression analysis was performed to identify significant imaging features in distinguishing between CIFRS and SNSCC. The ROC curves and the AUC were used to evaluate diagnostic performance.

Results: There were significant differences in cavernous sinus involvement (p < 0.001), sphenoid sinus involvement (p < 0.001), meningeal involvement (p = 0.024), T2 signal intensity (p = 0.006), and enhancement pattern (p < 0.001) between CIFRS and SNSCC. Multivariate logistic regression analysis identified cavernous sinus involvement (odds ratio [OR] = 0.06, 95% confidence interval [95% CI] = 0.02-0.20) and sphenoid sinus involvement (OR = 0.14, 95% CI = 0.05-0.45) as significant indicators for CIFRS and T2 isointensity to gray matter (OR = 4.44, 95% CI = 1.22-16.22) was a significant indicator for SNSCC. ROC curve analysis showed the AUC from a combination of three imaging features was 0.95 in differentiating CIFRS and SNSCC.

Conclusions: MRI showed significant differences between CIFRS and SNSCC features. In immunocompromised patients, a sinonasal hypointense mass on T2WI with septal enhancement or loss of contrast enhancement, and involvement of cavernous sinus, sphenoid sinus, and meninges strongly suggest CIFRS.

Key Points: • Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from sinonasal squamous cell carcinomas (SNSCC) in clinical practice. • Cavernous sinus and sphenoid sinus involvement appear to be significant indicators for CIFRS. T2 isointensity to gray matter appears to be a significant indicator for SNSCC. • Loss of contrast enhancement and septal enhancement can be used to distinguish CIFRS from SNSCC with a high degree of specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-06838-1DOI Listing
August 2020
-->