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Toppila‐Salmi S, Reitsma S, Hox V, Gane S, Eguiluz‐Gracia I, Shamji M, Maza‐Solano J, Jääskeläinen B, Väärä R, Escribese MM, Chaker A, Karavelia A, Rudenko M, Gevaert P, Klimek L. Endotyping in Chronic Rhinosinusitis-An EAACI Task Force Report. Allergy 2025; 80:132-147. [PMID: 39641584 PMCID: PMC11724251 DOI: 10.1111/all.16418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/12/2024] [Accepted: 11/18/2024] [Indexed: 12/07/2024]
Abstract
Chronic rhinosinusitis (CRS) is a clinical syndrome defined by typical sinonasal symptoms persisting for at least 12 weeks. CRS is divided into two distinct phenotypes, CRS with nasal polyps (CRSwNP) and without (CRSsNP). The aim of the review is to provide an update on the current knowledge in CRS endotypes. The prevailing hypothesis regarding the pathogenesis of CRS suggests that dysfunctional interactions between the host and environmental stressors at the mucosal surface drive the diverse inflammatory mechanisms. Genetic and epigenetic variations in the mucosal immune system are believed to play a significant role in the pathomechanisms of CRS. Various environmental agents (such as microbes and irritants) have been implicated in CRS. In a healthy state, the sinonasal mucosa acts as a barrier, modulating environmental stimulation and mounting appropriate immune responses against pathogens with minimal tissue damage. Different endotypes may exist based on the specific mechanistic pathways driving the chronic tissue inflammation of CRS. There is a need to understand endotypes in order to better predict, diagnose, and treat CRS. This literature review provides an update on the role of the endotypes in CRS and the limitations of endotyping CRS in clinical practice. Understanding of the pathogenesis and optimal management of CRS has progressed significantly in the last decades; however, there still are several unmet needs in endotype research.
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Affiliation(s)
- Sanna Toppila‐Salmi
- Department of OtorhinolaryngologyUniversity of Eastern FinlandKuopioFinland
- Department of OtorhinolaryngologyWellbeing Services County of Pohjois‐SavoKuopioFinland
- Inflammation Center, Department of AllergologyHelsinki University Hospital and University of HelsinkiHelsinkiFinland
| | - Sietze Reitsma
- Department of Otorhinolaryngology/Head‐Neck SurgeryAmsterdam University Medical Center, University of AmsterdamAmsterdamThe Netherlands
| | - Valérie Hox
- Department of Otorhinolaryngology, Head and Neck SurgeryCliniques Universitaires Saint‐LucBrusselsBelgium
| | - Simon Gane
- Royal National Ear, Nose and Throat and Eastman Dental HospitalUniversity College London Hospitals NHS TrustLondonUK
| | - Ibon Eguiluz‐Gracia
- Allergy UnitHospital Regional Universitario de Malaga. IBIMA‐Plataforma BIONAND. RICORS Enfermedades InflamatoriasMalagaSpain
| | - Mohamed Shamji
- National Heart and Lung InstituteImperial College LondonLondonUK
| | - Juan Maza‐Solano
- Rhinology and Skull Base Unit, Department of OtolaryngologyUniversity Hospital Virgen MacarenaSevilleSpain
- Department of SurgeryUniversity of SevilleSevilleSpain
| | | | - Risto Väärä
- Department of OtorhinolaryngologyUniversity of Eastern FinlandKuopioFinland
| | - Maria M. Escribese
- Institute of Applied Molecular Medicine Instituto de Medicina Molecular Aplicada Nemesio Díez (IMMA), Department of Basic Medical Sciences, Facultad de MedicinaUniversidad San Pablo‐CEU, CEU UniversitiesMadridSpain
| | - Adam Chaker
- Department of Otorhinolaryngology and Center for Allergy and EnvironmentTechnische Universität MünchenMünchenGermany
| | - Aspasia Karavelia
- Department of OtorhinolaryngologyGeneral Hospital of NafplioNafplioGreece
| | | | - Philippe Gevaert
- Upper Airways Research Laboratory, Department of Head and SkinGhent UniversityGhentBelgium
| | - Ludger Klimek
- Center for Rhinology and AllergologyWiesbadenGermany
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Lai S, Kang W, Chen Y, Zou J, Wang S, Zhang X, Zhang X, Lin Y. An End-to-End CRSwNP Prediction with Multichannel ResNet on Computed Tomography. Int J Biomed Imaging 2024; 2024:4960630. [PMID: 38883273 PMCID: PMC11178416 DOI: 10.1155/2024/4960630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 04/21/2024] [Accepted: 05/08/2024] [Indexed: 06/18/2024] Open
Abstract
Chronic rhinosinusitis (CRS) is a global disease characterized by poor treatment outcomes and high recurrence rates, significantly affecting patients' quality of life. Due to its complex pathophysiology and diverse clinical presentations, CRS is categorized into various subtypes to facilitate more precise diagnosis, treatment, and prognosis prediction. Among these, CRS with nasal polyps (CRSwNP) is further divided into eosinophilic CRSwNP (eCRSwNP) and noneosinophilic CRSwNP (non-eCRSwNP). However, there is a lack of precise predictive diagnostic and treatment methods, making research into accurate diagnostic techniques for CRSwNP endotypes crucial for achieving precision medicine in CRSwNP. This paper proposes a method using multiangle sinus computed tomography (CT) images combined with artificial intelligence (AI) to predict CRSwNP endotypes, distinguishing between patients with eCRSwNP and non-eCRSwNP. The considered dataset comprises 22,265 CT images from 192 CRSwNP patients, including 13,203 images from non-eCRSwNP patients and 9,062 images from eCRSwNP patients. Test results from the network model demonstrate that multiangle images provide more useful information for the network, achieving an accuracy of 98.43%, precision of 98.1%, recall of 98.1%, specificity of 98.7%, and an AUC value of 0.984. Compared to the limited learning capacity of single-channel neural networks, our proposed multichannel feature adaptive fusion model captures multiscale spatial features, enhancing the model's focus on crucial sinus information within the CT images to maximize detection accuracy. This deep learning-based diagnostic model for CRSwNP endotypes offers excellent classification performance, providing a noninvasive method for accurately predicting CRSwNP endotypes before treatment and paving the way for precision medicine in the new era of CRSwNP.
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Affiliation(s)
- Shixin Lai
- College of Engineering Shantou University, Shantou 515063, China
| | - Weipiao Kang
- Department of Otolaryngology Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
| | - Yaowen Chen
- College of Engineering Shantou University, Shantou 515063, China
| | - Jisheng Zou
- College of Engineering Shantou University, Shantou 515063, China
| | - Siqi Wang
- College of Engineering Shantou University, Shantou 515063, China
| | - Xuan Zhang
- College of Engineering Shantou University, Shantou 515063, China
| | - Xiaolei Zhang
- Department of Radiology Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
| | - Yu Lin
- Department of Otolaryngology Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
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Li YT, Huang SS, Ma JH, Hsieh BH, Tsou YA, Lin CD, Tai CJ, Shih LC. Bacteriology of Different Phenotypes of Chronic Rhinosinusitis. Laryngoscope 2024; 134:1071-1076. [PMID: 37477266 DOI: 10.1002/lary.30905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 07/03/2023] [Accepted: 07/07/2023] [Indexed: 07/22/2023]
Abstract
OBJECTIVES Chronic rhinosinusitis (CRS) reduces the health-related quality of life and subsequently causes a tremendous socio-economic impact. Although many studies have been conducted, few have identified a relationship between bacteriological characteristics and different phenotypes or endotypes. Therefore, this study aimed to elucidate the recent trends in bacterial cultures from different types of CRS in the Asian population. METHODS This retrospective case-control study recruited patients diagnosed with CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into those with chronic rhinosinusitis with nasal polyps (CRSwNP)/chronic rhinosinusitis without nasal polyps (CRSsNP), eosinophilic chronic rhinosinusitis (eCRS)/non-eosinophilic chronic rhinosinusitis (NECRS), and central compartment atopic disease (CCAD)/lateral-dominant nasal polyp (LDNP) groups. The demographic data and bacteriological characteristics of the groups were analyzed. RESULTS We included 503 patients, identifying no significant difference between CRSwNP and CRSsNP for several common bacteria in CRS. The number of Staphylococcus epidermidis isolates in culture was significantly higher in the NECRS group (50.46% vs. 32.56%, p = 0.0003) than that in the eCRS group. The number of methicillin-resistant Staphylococcus aureus (MRSA; 8.51% vs. 2.35%, p = 0.0221) positive isolates was significantly higher in the CCAD group than that in the LDNP group. CONCLUSIONS This was the first study in Asia to analyze the relationship between bacteriological characteristics and CCAD. MRSA is significantly higher in the CCAD group than that in the LDNP group. Recognizing the unique microbiology of CRSwNP, eCRS, and CCAD is crucial when selecting antimicrobial therapy to lessen the socio-economic impact. LEVEL OF EVIDENCE 3 Laryngoscope, 134:1071-1076, 2024.
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Affiliation(s)
- Yu-Ting Li
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Shuang-Shuang Huang
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Jia-Hung Ma
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Bing-Han Hsieh
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Yung-An Tsou
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
- Department of Otorhinolaryngology-Head and Neck Surgery, Asia University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chia-Der Lin
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chih-Jaan Tai
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Liang-Chun Shih
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan
- Department of Otorhinolaryngology-Head and Neck Surgery, Asia University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
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Kang YF, Liu JX, Xu K, Li XL, Lu X. sPLA2GIB Promotes PGD2 and IL-13 Production in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps. Laryngoscope 2024; 134:1107-1117. [PMID: 37594194 DOI: 10.1002/lary.30977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 08/19/2023]
Abstract
OBJECTIVE Secreted phospholipase A2 Group IB (sPLA2GIB) regulates the release of arachidonic acid, prostaglandins, and other inflammatory lipid mediators. Although it has been well involved in extensive inflammatory diseases, its specific mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. In this study, we investigated the role of sPLA2GIB in the pathophysiology of CRSwNP. METHODS Quantitative PCR, immunofluorescence staining, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to analyze the expression of sPLA2s, phospholipase A2 receptor (PLA2R), and prostaglandin D2 (PGD2) in nasal samples. Human nasal epithelial cells (HNECs) were cultured at an air-liquid interface (ALI) and stimulated with various cytokines. The human mast cell line HMC-1 was stimulated with sPLA2GIB, and the expression of PGD2 and cytokines in the culture supernatant was detected by ELISA. RESULTS The mRNA and protein levels of sPLA2GIB were significantly higher in eosinophilic CRSwNP than in control tissues. sPLA2GIB was predominantly expressed in the nasal epithelial cells. PLA2R mRNA and protein levels were upregulated in both eosinophilic and non-eosinophilic CRSwNP compared with the control groups. IL-4, IL-13, TNF-α, and IL-1β upregulated the expression of sPLA2GIB in ALI-cultured HNECs. sPLA2GIB induced PGD2 and IL-13 production in HMC-1 cells in a hydrolytic activity-independent manner. PGD2 protein expression was elevated in tissue homogenates of eosinophilic CRSwNP, and PGD2 upregulated the expression of IL-13 in HMC-1 cells. CONCLUSION Increased secretion of sPLA2GIB by epithelial cells may promote eosinophilic inflammation in CRSwNP by enhancing PGD2 and IL-13 production in mast cells via binding to PLA2R. LEVEL OF EVIDENCE N/A Laryngoscope, 134:1107-1117, 2024.
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Affiliation(s)
- Yi-Fan Kang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Jin-Xin Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Kai Xu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xue-Li Li
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xiang Lu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
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Kariyawasam HH, James LK. Chronic rhinosinusitis with nasal polyps: eosinophils versus B lymphocytes in disease pathogenesis. Curr Opin Allergy Clin Immunol 2024; 24:15-24. [PMID: 38018818 DOI: 10.1097/aci.0000000000000959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2023]
Abstract
PURPOSE OF REVIEW To highlight the current evidence that supports the view that eosinophils may not drive disease in chronic rhinosinusitis with nasal polyps (CRSwNP) and the emerging evidence for B cells as an important player in this disease. RECENT FINDINGS Eosinophil depletion studies in CRSwNP do not fully support a critical role for eosinophils in CRSwNP. Almost complete eosinophil depletion with dexpramipexole had no impact on polyp size reduction or clinical improvement. Anti-interleukin (IL)-5 and IL-5Rα inhibition were more effective though with less clinical impact when compared to anti-immunoglobulin E (IgE) or IL-4Rα inhibition strategies. As IL-5Rα is also expressed on CRSwNP derived IgE+ and IgG4+ plasma cells to the same extent as eosinophils, improvements in CRSwNP with IL-5 inhibition may suggest a role for B cells over eosinophils in CRSwNP. We review both eosinophils and B cells in the context of CRSwNP and highlight the current evidence that supports an emerging role for B cells. SUMMARY Despite many aspects of immunopathology in CRSwNP explainable by B cell dysfunction, B cells have so far been ignored in CRSwNP. Further work is needed, as targeting B cells may offer an exciting new therapeutic option in the future.
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Affiliation(s)
- Harsha H Kariyawasam
- Specialist Allergy and Clinical Immunology, Royal National ENT and Eastman Hospital, London
- Department of Rhinology, Royal National ENT and Eastman Hospital, London, University College London Hospitals NHS Foundation Trust
| | - Louisa K James
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Vollmer C, Dias A, Sales M, Sacramento PM, Silva JC, Oyamada HAA, Linhares UC, Gupta S, Kasahara TM, Bento CAM. Leptin favors imbalance of antigen-specific CD4 + T-cells associated with severity of cat allergy. Front Immunol 2023; 14:1290740. [PMID: 37954580 PMCID: PMC10639137 DOI: 10.3389/fimmu.2023.1290740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/09/2023] [Indexed: 11/14/2023] Open
Abstract
Introduction Obesity can complicate IgE-mediated allergic diseases. In the present study, we aimed to investigate the ability of obesity-related concentrations of leptin to modulate the in vitro effector and regulatory Fel d1-specific CD4+ T-cell subsets in patients allergic to cat, considered the third most common cause of respiratory allergy in humans. Methods For this study, plasma and peripheral blood mononuclear cells (PBMC) from 30 cat-allergic patients with mild, moderate and severe respiratory symptoms were obtained. The PBMC cultures were stimulated with Fel d1 antigen (10 µg/mL) in the presence or absence of obesity-related leptin dose (50 ηg/mL). After 6 days, the levels of cytokines and IgE in the supernatants were evaluated by multiplex and ELISA, respectively. The frequency of different non-follicular (CXCR5-) and follicular (CXCR5+) Fel d1-specific CD4+ T cell subsets was determined by flow cytometry. The plasma levels of leptin and IgE anti-cat titers were evaluated by ELISA and ImmunoCAP, respectively. Results and conclusions Fel d1 induced both IgE production and release of cytokines related to Th2, Th9 and Th17 cell phenotypes. Feld1 was more efficient in increasing the frequency of TFHIL-21- cells positive for IL-4, IL-5 and IL-13 than TFHIL-21+ cell subsets. Leptin favored the expansion Th2-like and Th9-like cells and TFHIL-21- cells positive for IL-4, IL-5 and IL-13, but reduced the proportion of conventional (Treg/Tr-1) and follicular (TFR) regulatory CD4+ T-cell subsets expressing or not CD39 marker. Finally, many of the imbalances between Fel d1-specific CD4+ T-cells were also correlated with plasma leptin and anti-Fel d1 IgE titers. In summary, hyperleptinemia should negatively impact on the severity of cat allergies by favoring the expansion of pathogenic Fel d1-specific CD4+ T-cell phenotypes and damaging the functional status of regulatory CD4+ T-cell subsets.
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Affiliation(s)
- Carolina Vollmer
- Post-graduate Program in Cellular and Molecular Biology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Aleida Dias
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marisa Sales
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Priscila M. Sacramento
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Júlio Cesar Silva
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Hugo A. A. Oyamada
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ulisses C. Linhares
- Department of Morphological Sciences, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sudhir Gupta
- Department of Medicine, University of California, Irvine, Irvine, CA, United States
| | - Taissa M. Kasahara
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Cleonice A. M. Bento
- Post-graduate Program in Cellular and Molecular Biology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
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Ha JG, Cho HJ. Unraveling the Role of Epithelial Cells in the Development of Chronic Rhinosinusitis. Int J Mol Sci 2023; 24:14229. [PMID: 37762530 PMCID: PMC10531804 DOI: 10.3390/ijms241814229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
The pathophysiology of CRS is multifactorial and complex yet needs to be completed. Recent evidence emphasizes the crucial part played by epithelial cells in the development of CRS. The epithelial cells act as physical barriers and play crucial roles in host defense, including initiating and shaping innate and adaptive immune responses. This review aims to present a comprehensive understanding of the significance of nasal epithelial cells in CRS. New research suggests that epithelial dysfunction plays a role in developing CRS through multiple mechanisms. This refers to issues with a weakened barrier function, disrupted mucociliary clearance, and irregular immune responses. When the epithelial barrier is compromised, it can lead to the passage of pathogens and allergens, triggering inflammation in the body. Furthermore, impaired mucociliary clearance can accumulate pathogens and secretions of inflammatory mediators, promoting chronic inflammation. Epithelial cells can release cytokines and chemokines, which attract and activate immune cells. This can result in an imbalanced immune response that continues to cause inflammation. The interaction between nasal epithelial cells and various immune cells leads to the production of cytokines and chemokines, which can either increase or decrease inflammation. By comprehending the role of epithelial cells in CRS, we can enhance our understanding of the disease's pathogenesis and explore new therapeutics.
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Affiliation(s)
- Jong-Gyun Ha
- Department of Otorhinolaryngology—Head and Neck Surgery, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong 14353, Republic of Korea;
| | - Hyung-Ju Cho
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- The Airway Mucus Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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Laidlaw TM, Menzies-Gow A, Caveney S, Han JK, Martin N, Israel E, Lee JK, Llanos JP, Martin N, Megally A, Parikh B, Vong S, Welte T, Corren J. Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR. J Asthma Allergy 2023; 16:915-932. [PMID: 37692126 PMCID: PMC10488831 DOI: 10.2147/jaa.s413064] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Purpose Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR. Methods Patients with severe asthma (N=1059) were randomized (1:1) and received tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. Prespecified exploratory analyses included: AAER over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 were assessed (post hoc). Results Tezepelumab reduced the AAER over 52 weeks versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, tezepelumab improved lung function, asthma control and HRQoL versus placebo in patients with and without NPs. Tezepelumab reduced SNOT-22 total scores (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 28 weeks (-12.57 points [-19.40, -5.73]) and 52 weeks (-10.58 points [-17.75, -3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status. Conclusion Tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.
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Affiliation(s)
- Tanya M Laidlaw
- Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Andrew Menzies-Gow
- Royal Brompton and Harefield Hospitals, School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Scott Caveney
- Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA
| | - Joseph K Han
- Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, VA, USA
| | - Nicole Martin
- Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA
- Cytel Inc, Waltham, MA, USA
| | - Elliot Israel
- Divisions of Pulmonary and Critical Care Medicine and Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Jason K Lee
- Evidence Based Medical Educator Inc., Toronto, ON, Canada
- Toronto Allergy and Asthma Clinic, Toronto, ON, Canada
| | | | - Neil Martin
- Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK
- University of Leicester, Leicester, UK
| | - Ayman Megally
- Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | - Bhavini Parikh
- Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | - Sylvia Vong
- Translational Science and Experimental Medicine, Early Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA
| | - Tobias Welte
- Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany
| | - Jonathan Corren
- David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
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Cakir Cetin A, Tuncok Y, Keskinoglu P, Arici MA, Onen F, Ecevit MC. Methotrexate for recurrent chronic rhinosinusitis with nasal polyps: A randomized, controlled, phase 2 clinical trial. Int Forum Allergy Rhinol 2023; 13:1592-1602. [PMID: 36575820 DOI: 10.1002/alr.23131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 12/06/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVE This randomized, controlled, open-label, phase 2 clinical trial aimed to assess the efficacy and safety of low-dose methotrexate as maintenance therapy for recurrent postoperative chronic rhinosinusitis with nasal polyps (CRSwNPs). METHODS Forty-one patients with CRSwNPs who experienced postoperative polyp recurrence(s) were randomly divided into three groups to receive one of the following treatments for 8 weeks: daily intranasal mometasone furoate monohydrate 200 mcg (control [intranasal corticosteroids (INCS)] arm, n = 13]); daily per oral methylprednisolone 8 mg (oral corticosteroids [OCS] arm, n = 14); and once weekly per oral 10 mg methotrexate (MTX arm, n = 14). All patients were assessed at three clinical visits according to the Lund-Kennedy endoscopic grading system (LKES), visual analog scale (VAS), Turkish version of the Sinonasal Outcome Test-22 (SNOT-22), peak nasal inspiratory flow (PNIF), butanol olfactory threshold test (BuOT), serum total IgE level, presence of peripheral eosinophilia, serum biochemical assays, and adverse events. RESULTS All efficacy outcome measures significantly improved in all three groups, except for the nonrecovery of peripheral eosinophilia in the INCS group. There was no significant difference among the groups in terms of LKES scores. Scores for the Turkish version of the SNOT-22, PNIF, BuOT, and serum IgE levels were also similar among the groups. However, total VAS scores recovered significantly better in the INCS group than in the MTX group. Serum biochemical assays remained normal in all groups. Adverse events were minor and observed only in the OCS group. CONCLUSION Low-dose MTX was a safe and effective maintenance therapy for patients with recurrent postoperative CRSwNPs.
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Affiliation(s)
- Asli Cakir Cetin
- Department of Otorhinolaryngology, Dokuz Eylul University Medical School, Izmir, Turkey
| | - Yesim Tuncok
- Department of Medical Pharmacology, Dokuz Eylul University Medical School, Izmir, Turkey
| | - Pembe Keskinoglu
- Department of Biostatistics and Informatics, Dokuz Eylul University Medical School, Izmir, Turkey
| | - Mualla Aylin Arici
- Department of Medical Pharmacology, Dokuz Eylul University Medical School, Izmir, Turkey
| | - Fatos Onen
- Department of Rheumatology and Immunology, Dokuz Eylul University Medical School, Izmir, Turkey
| | - Mustafa Cenk Ecevit
- Department of Otorhinolaryngology, Dokuz Eylul University Medical School, Izmir, Turkey
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10
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Zhou A, Shi C, Fan Y, Zheng Y, Wang J, Liu Z, Xie H, Liu J, Jiao Q. Involvement of CD40-CD40L and ICOS-ICOSL in the development of chronic rhinosinusitis by targeting eosinophils. Front Immunol 2023; 14:1171308. [PMID: 37325657 PMCID: PMC10267736 DOI: 10.3389/fimmu.2023.1171308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 03/20/2023] [Indexed: 06/17/2023] Open
Abstract
Background Chronic rhinosinusitis (CRS), whose prevalence and pathogenesis are age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and inducible co-stimulator (ICOS)-ICOS ligand (ICOSL) signal can strengthen CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the development of CRS remains unknown. Objectives The aim of this study is to investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms. Methods Immunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-localizations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils. Results Compared with the non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, whereas ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from patients with ECRS. Tumor necrosis factor-α (TNF-α) and interleukin-5 (IL-5) obviously upregulated CD40 expression on eosinophils, which was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor. Conclusions Increased CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-α and IL-5 regulate eosinophils function by increasing CD40 expression partly via p38 MAPK activation in patients with CRS.
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Affiliation(s)
- Aina Zhou
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chenxi Shi
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuhui Fan
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yushuang Zheng
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jue Wang
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhichen Liu
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Huanxia Xie
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jisheng Liu
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qingqing Jiao
- Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China
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11
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Liu JX, Chen AN, Yu Q, Shi KT, Liu YB, Guo CL, Wang ZZ, Yao Y, Pan L, Lu X, Xu K, Wang H, Zeng M, Liu C, Schleimer RP, Wu N, Liao B, Liu Z. MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability. JCI Insight 2023; 8:e159058. [PMID: 36976645 PMCID: PMC10243817 DOI: 10.1172/jci.insight.159058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-β receptor III (TGFBR3) mRNA level by binding to its 3' UTR and reducing its stability in HNECs. TGF-βR3 was found to be a TGF-β2-specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-β2-induced phosphorylation of SMAD2 in HNECs, respectively. TGF-βR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-β2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-βR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.
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Affiliation(s)
- Jin-Xin Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Ao-Nan Chen
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Qihong Yu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Ke-Tai Shi
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Yi-Bo Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Cui-Lian Guo
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Zhe-Zheng Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Li Pan
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Xiang Lu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Kai Xu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Heng Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Chaohong Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Robert P. Schleimer
- Division of Allergy-Immunology, Department of Medicine; and
- Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Ning Wu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
- Department of Immunology, School of Basic Medicine, Tongji Medical College, and
- Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Liao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital; and
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12
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Yao Y, Zhu HY, Zeng M, Liu Z. Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia: A narrative review. Clin Otolaryngol 2023; 48:363-370. [PMID: 36317525 DOI: 10.1111/coa.14001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/23/2022] [Accepted: 10/16/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia. DESIGN This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment. RESULTS AND CONCLUSION CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.
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Affiliation(s)
- Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, Hubei, People's Republic of China
| | - Hong-Yu Zhu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, Hubei, People's Republic of China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, Hubei, People's Republic of China
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13
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Bai J, Tan BK. B Lineage Cells and IgE in Allergic Rhinitis and CRSwNP and the Role of Omalizumab Treatment. Am J Rhinol Allergy 2023; 37:182-192. [PMID: 36848269 PMCID: PMC10830379 DOI: 10.1177/19458924221147770] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
BACKGROUND Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two prevalent nasal diseases where both type 2 inflammation and immunoglobulin E (IgE) may play important roles. Although they can exist independently or comorbidly, subtle but important differences exist in immunopathogenesis. OBJECTIVE To summarize current knowledge of pathophysiological roles of B lineage cells and IgE in AR and CRS with nasal polyps (CRSwNP). METHODS Searched PubMed database, reviewed AR and CRSwNP-related literature, and discussed disease diagnosis, comorbidity, epidemiology, pathophysiology, and treatment. Similarities and differences in B-cell biology and IgE are compared in the 2 conditions. RESULTS Both AR and CRSwNP have evidence for pathological type 2 inflammation, B-cell activation and differentiation, and IgE production. However, distinctions exist in the clinical and serological profiles at diagnosis, as well as treatments utilized. B-cell activation in AR may more frequently be regulated in the germinal center of lymphoid follicles, whereas CRSwNP may occur via extrafollicular pathways although controversies remain in these initial activating events. Oligoclonal and antigen-specific IgE maybe predominate in AR, but polyclonal and antigen-nonspecific IgE may predominate in CRSwNP. Omalizumab has been shown efficacious in treating both AR and CRSwNP in multiple clinical trials but is the only Food and Drug Administration-approved anti-IgE biologic to treat CRSwNP or allergic asthma. Staphylococcus aureus frequently colonizes the nasal airway and has the ability to activate type two responses including B-cell responses although the extent to which it modulates AR and CRSwNP disease severity is being investigated. CONCLUSION This review highlights current knowledge of the roles of B cells and IgE in the pathogenesis of AR and CRSwNP and a small comparison between the 2 diseases. More systemic studies should be done to elevate the understanding of these diseases and their treatment.
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Affiliation(s)
- Junqin Bai
- Department of Otolaryngology, 12244Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Bruce K Tan
- Department of Otolaryngology, 12244Northwestern University Feinberg School of Medicine, Chicago, Illinois
- Division of Allergy and Immunology, Department of Medicine, 12244Northwestern University Feinberg School of Medicine, Chicago, Illinois
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14
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Nie Z, Xu Z, Fan Y, Guo Y, Chen C, Liu W, Li Y, Lai Y, Shi J, Chen F. Clinical characteristics of central compartment atopic disease in Southern China. Int Forum Allergy Rhinol 2023; 13:205-215. [PMID: 35900084 DOI: 10.1002/alr.23069] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 07/12/2022] [Accepted: 07/25/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND Central compartment atopic disease (CCAD) is a newly reported subset of chronic rhinosinusitis. It was considered associated with inhalant antigen. However, CCAD in Chinese population is not fully studied yet. DESIGN Prospective cohort study. OBJECTIVE This study aimed to describe the clinical manifestations of CCAD and compared the following two subtypes: sinonasal polyps and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Also, we compared the clinical manifestations of atopy CCAD and non-atopy CCAD. METHODS We consecutively enrolled CRSwNP patients without prior sinus surgery, and assessed the nasal endoscopy and computed tomography of the paranasal sinuses. Allergy was confirmed by skin or serum testing. Eosinophilic CRSwNP (ECRS) was considered as tissue eosinophils to total inflammatory cells >10%. RESULTS We enrolled a total of 116 patients, including 39 with CCAD, 38 with CRSwNP/CC and 39 with CRSwNP NOS. Atopy was detected in 37.1% of the CCAD group, an incidence showing no significant difference from those in the other two groups (37.1% in the CRSwNP/CC group, 31.0% in the CRSwNP NOS group; p = 0.846). However, the incidence of ECRS in the CCAD group was the highest among the different groups (97.4% in the CCAD group vs. 67.6% in the CRSwNP/CC group vs. 35.1% in the CRSwNP NOS group; p = 0.000). In addition, the incidence of asthma in the CCAD group (33.3%) was significantly higher than that in the CRSwNP NOS group (10.3%), but quite similar to CRSwNP/CC (34.2%). In the subgroup analysis of CCAD, only total serum IgE and sIgE demonstrated significant differences between atopy CCAD and non-atopy CCAD. CONCLUSION CCAD in Southern China may associate with asthma and significant eosinophilia, with a lower incidence of systemic allergy based on skin and serum testing.
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Affiliation(s)
- Zhiying Nie
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhaofeng Xu
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yunping Fan
- Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Yuanyuan Guo
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Chuxin Chen
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Wendong Liu
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yueqi Li
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yinyan Lai
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jianbo Shi
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fenghong Chen
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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15
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Santomasi C, Buonamico E, Dragonieri S, Iannuzzi L, Portacci A, Quaranta N, Carpagnano GE. Effects of benralizumab in a population of patients affected by severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: a real life study. ACTA BIO-MEDICA : ATENEI PARMENSIS 2023; 94:e2023028. [PMID: 36786266 PMCID: PMC9987478 DOI: 10.23750/abm.v94i1.13474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 08/04/2022] [Indexed: 02/15/2023]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe eosinophilic asthma (SEA), which may contribute to the loss of asthma control. CRSwNP and SEA share a T2-mediated mechanism and the use of some anti-asthma monoclonal antibodies has recently been extended to CRSwNP. Unlike dupilumab and omalizumab, benralizumab approval for CRSwNP is ongoing. We aimed to evaluate the efficacy of benralizumab efficacy on SEA and on CRSwNP in patients affected by both pathologies in a real life setting. METHODS 17 patients affected by both SEA and CRSwNP participated to our study. At baseline (T0) and at one year after benralizumab initiation (T1), all participants underwent spirometry, exhaled nitric oxide (FeNO), Asthma Control Test (ACT), nasal endoscopy with Nasal Polyp Score (NPS), nasal cytology and Sino-Nasal Outcome Test 22 (SNOT 22).The continuous oral corticosteroid therapy (OCS), the number of year exacerbations and the need for sinus surgery were also evaluated for each patient. RESULTS At T1, a marked reduction of SNOT-22, NPS, nasal eosinophils and neutrophils count were shown compared to T0. Moreover, at T1 ACT was significantly increased and FeNO, exacerbations/year and mean OCS dosage were significantly reduced compared to T0. CONCLUSIONS Our real-life study demonstrates the efficacy of benralizumab not only on SEA but also on nasal cytology and on nasal polyposis, confirming that patients affected by both SEA and CRSwNP may receive a considerable benefit from anti-IL5 receptor, treating both the comorbidities at once.
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16
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Zhipu N, Zitao H, Jichao S, Cuida M. Research advances in roles of microRNAs in nasal polyp. Front Genet 2022; 13:1043888. [PMID: 36506304 PMCID: PMC9732428 DOI: 10.3389/fgene.2022.1043888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 11/14/2022] [Indexed: 11/27/2022] Open
Abstract
MicroRNAs (miRNAs), a subset of endogenous RNAs highly conservative with short chains, play key regulatory role in the biological relevant events of the cells. Exosomes are extracellular vesicles like the plasma membrane components being able to deliver information molecules such as miRNA between cells and to regulate the fate of the target cells. The progression of chronic rhinosinusitis with nasal polyps (CRSwNP) is closely associated with significant alterations of miRNA levels in both cells and exosomes. RNA-binding proteins (RBPs) have been acknowledged to play important roles in intracellular miRNA transport to exosomes, and specific membrane proteins such as caveolin-1 critically involved in HNRNPA1 -mediated transport of miRNA to exosomes. Aberrant alteration in endogenous miRNA levels significantly contributes to the process of airway remodeling in the nasal tissue and to the occurrence and progression of inflammatory responses in CRSwNP. Exogenous miRNAs delivered via exosomes has also been shown to play an important role in activating macrophages or in regulating vascular permeability in the CRSwNP.This paper highlights the mechanism of RBP-mediated delivery of miRNAs to exosomes and the important contribution of endogenous miRNAs to the development of CRSwNP in response to inflammation and airway remodeling. Finally, we discuss the future research directions for regulation of the miRNAs to CRSwNP.Delivery of exogenous miRNAs by exosomes alters the endogenous miRNAs content in nasal mucosal epithelial cells or in associated inflammatory cells in the CRSwNP, and altered endogenous miRNAs affects the inflammatory response and airway remodeling, which then regulates the occurrence and progression of CRSwNP.RBPs and associated membrane proteins such as caveolin-1 may play a crucial role in the entry of exogenous miRNA into exosomes.
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Affiliation(s)
- Niu Zhipu
- Clinical Medicine, China-Japan Union Hospital of Jilin University Norman Bethune Third School of Jilin University, Changchun, China
| | - Huo Zitao
- Clinical Medicine, China-Japan Union Hospital of Jilin University Norman Bethune Third School of Jilin University, Changchun, China
| | - Sha Jichao
- Department of Otorhinolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University Norman Bethune Third School of Jilin University, Changchun, China,*Correspondence: Sha Jichao, ; Meng Cuida,
| | - Meng Cuida
- Department of Otorhinolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University Norman Bethune Third School of Jilin University, Changchun, China,*Correspondence: Sha Jichao, ; Meng Cuida,
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17
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Zhu Y, Sun X, Tan S, Luo C, Zhou J, Zhang S, Li Z, Lin H, Zhang W. M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps. Front Immunol 2022; 13:1047930. [PMID: 36466903 PMCID: PMC9712459 DOI: 10.3389/fimmu.2022.1047930] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/02/2022] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP. METHODS The expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results. RESULTS A total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP. CONCLUSION These findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.
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Affiliation(s)
- Ying Zhu
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Xiwen Sun
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Shaolin Tan
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Chunyu Luo
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Jiayao Zhou
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Shiyao Zhang
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Zhipeng Li
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Hai Lin
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
| | - Weitian Zhang
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Shanghai, China
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18
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Czerwaty K, Piszczatowska K, Brzost J, Ludwig N, Szczepański MJ, Dżaman K. Immunological Aspects of Chronic Rhinosinusitis. Diagnostics (Basel) 2022; 12:diagnostics12102361. [PMID: 36292050 PMCID: PMC9600442 DOI: 10.3390/diagnostics12102361] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic rhinosinusitis (CRS) is related to persistent inflammation with a dysfunctional relationship between environmental agents and the host immune system. Disturbances in the functioning of the sinus mucosa lead to common clinical symptoms. The major processes involved in the pathogenesis of CRS include airway epithelial dysfunctions that are influenced by external and host-derived factors which activate multiple immunological mechanisms. The molecular bases for CRS remain unclear, although some factors commonly correspond to the disease: bacterial, fungal and viral infections, comorbidity diseases, genetic dysfunctions, and immunodeficiency. Additionally, air pollution leads increased severity of symptoms. CRS is a heterogeneous group of sinus diseases with different clinical courses and response to treatment. Immunological pathways vary depending on the endotype or genotype of the patient. The recent knowledge expansion into mechanisms underlying the pathogenesis of CRS is leading to a steadily increasing significance of precision medicine in the treatment of CRS. The purpose of this review is to summarize the current state of knowledge regarding the immunological aspects of CRS, which are essential for ensuring more effective treatment strategies.
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Affiliation(s)
- Katarzyna Czerwaty
- Department of Otolaryngology, The Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland
| | | | - Jacek Brzost
- The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
| | - Nils Ludwig
- Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Mirosław J. Szczepański
- Department of Otolaryngology, The Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland
- Correspondence:
| | - Karolina Dżaman
- Department of Otolaryngology, The Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland
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Shen Y, Zhang N, Yang Y, Hong S, Bachert C. Local Immunoglobulin E in nasal polyps: Role and modulation. Front Immunol 2022; 13:961503. [PMID: 36159836 PMCID: PMC9492990 DOI: 10.3389/fimmu.2022.961503] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 08/19/2022] [Indexed: 11/29/2022] Open
Abstract
In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE’s characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen- Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-β, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.
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Affiliation(s)
- Yang Shen
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Nan Zhang
- Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium
| | - Yucheng Yang
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Suling Hong
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Claus Bachert
- Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium
- Division of Otorhinolaryngology Diseases, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
- *Correspondence: Claus Bachert,
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20
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Heffernan A, Phulka J, Thamboo A. Improving predictability of IgE-high type 2 chronic sinusitis with nasal polyps in the biologic era. J Otolaryngol Head Neck Surg 2022; 51:22. [PMID: 35606866 PMCID: PMC9128111 DOI: 10.1186/s40463-022-00580-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 05/12/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Chronic rhinosinusitis (CRS) is an inflammatory disease that may require biological therapy. Omalizumab is an anti-IgE biologic that was recently approved by the FDA and Health Canada for use in severe CRS with nasal polyps (CRSwNP) recalcitrant to intranasal corticosteroids. Dosing is based on weight and pre-treatment serum IgE, with elevated levels of the latter being an indication for biologic treatment according to EPOS and EUFOREA guidelines. The goal of this study was to identify variables that predict IgE-high type 2 inflammation and serve as indicators for biologic treatment in CRS. METHODS Patients ≥ 19 yo diagnosed with CRS undergoing functional endoscopic sinus surgery were included retrospectively. Demographics, past medical history, preoperative blood work, Lund-Mackay (LM), Lund Kennedy (LK), and SNOT-22 scores were extracted. Descriptive statistics and binary logistic regression analyses were conducted. Model superiority was based on Nagelkerke R2 scores and receiver operating characteristic curves. RESULTS Sixty-five patients, average age 49.96 ± 13.59 years, were included. Sixty-one binary logistic regression models for elevated serum IgE were created. Among the top 3 models, the best model had sensitivity, specificity, positive predictive value and negative predictive values of 82.1, 69.2, 80.0, and 72.0. All performance measures except sensitivity exceeded the Canadian Biologics Guideline model. Serum eosinophils ≥ 300 cell/uL, CRSwNP and LM ≥ 17 increased the odds of elevated IgE. CONCLUSIONS IgE-high type-2 inflammation can be predicted by a model that includes eosinophil ≥ 300 cell/uL, CRSwNP, LM ≥ 17, asthma diagnosis and SNOT-22 ≥ 40. Patients meeting these parameters have a high pretest probability for elevated IgE and would benefit from IgE serology to determine qualification for omalizumab. This could reduce unwarranted IgE serology in patients with CRSwNP but also target a patient population for further workup that will lead to optimization of resource allocation and improve healthcare equity in rural and remote areas within Canada.
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Affiliation(s)
- Austin Heffernan
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, 2775 Laurel Street, 4th Floor, Vancouver, BC, V5Z 1M9, Canada
| | - Jobanjit Phulka
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, 2775 Laurel Street, 4th Floor, Vancouver, BC, V5Z 1M9, Canada
| | - Andrew Thamboo
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, 2775 Laurel Street, 4th Floor, Vancouver, BC, V5Z 1M9, Canada.
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, St. Paul's Hospital, Vancouver, BC, Canada.
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Akiyama M, Kaneko Y, Takeuchi T. T follicular helper cells mediate local production of allergen-specific IgE and IgG4. J Allergy Clin Immunol 2022; 150:1045-1047. [PMID: 35588899 DOI: 10.1016/j.jaci.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/04/2022] [Accepted: 05/10/2022] [Indexed: 10/18/2022]
Affiliation(s)
- Mitsuhiro Akiyama
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 1608582, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 1608582, Tokyo, Japan
| | - Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 1608582, Tokyo, Japan.
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22
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Calabrese C, Seccia V, Pelaia C, Spinelli F, Morini P, Rizzi A, Detoraki A. S. aureus and IgE-mediated diseases: pilot or copilot? A narrative review. Expert Rev Clin Immunol 2022; 18:639-647. [PMID: 35507006 DOI: 10.1080/1744666x.2022.2074402] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION S. aureus is a major opportunistic pathogen that has been implicated in the pathogenesis of several chronic inflammatory diseases including bronchial asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic spontaneous urticaria (CSU), and atopic dermatitis. S. aureus can induce the production of both polyclonal and specific IgE that can elicit an inflammatory cascade. AREAS COVERED The link between the sensitization to S. aureus enterotoxins and the severity of several chronic inflammatory diseases is reviewed in detail, as well as its therapeutic implications. EXPERT OPINION An anti-IgE strategy to inhibit S. aureus enterotoxins would be a valid approach to treat several endotypes of severe asthma, CRSwNP and CSU in which IgE against S. aureus enterotoxins should represent, not only a marker of severity of the diseases but also a target of a treatment.
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Affiliation(s)
- Cecilia Calabrese
- Department of Translational Medical Sciences, Institute of Respiratory Diseases, University of Campania "L. Vanvitelli", Naples, Italy
| | - Veronica Seccia
- Otolaryngology Audiology, and Phoniatric Operative Unit, Department of Surgical, Medical, Molecular Pathology, and Critical Care Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy
| | - Corrado Pelaia
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy
| | | | | | | | - Aikaterini Detoraki
- Division of Internal Medicine and Clinical Immunology, Department of Internal Medicine, Clinical Immunology, Clinical Pathology and Infectious Diseases, Azienda Ospedaliera Universitaria Federico II, Naples, Italy
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Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol 2022; 149:1491-1503. [PMID: 35245537 PMCID: PMC9081253 DOI: 10.1016/j.jaci.2022.02.016] [Citation(s) in RCA: 116] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 02/07/2022] [Accepted: 02/18/2022] [Indexed: 11/19/2022]
Abstract
Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and is historically divided into 2 main phenotypes: CRS with nasal polyps and CRS without nasal polyps. Inflammation in CRS is mainly characterized by 3 endotypes based on elevation of canonical lymphocyte cytokines: type (T) 1 (T1) by TH1 cytokine IFN-γ, T2 by TH2 cutokines IL-4, IL-5, and IL-13, and T3 by TH17 cytokines including IL-17. Inflammation in both CRS without nasal polyps and CRS with nasal polyps is highly heterogeneous, and the frequency of various endotypes varies geographically around the world. This finding complicates establishment of a unified understanding of the mechanisms of pathogenesis in CRS. Sinonasal epithelium acts as a passive barrier, and epithelial barrier dysfunction is a common feature in CRS induced by endotype-specific cytokines directly and indirectly. The sinonasal epithelium also participates in both innate immunity via recognition by innate pattern-recognition receptors and promotes and regulates adaptive immunity via release of chemokines and innate cytokines including thymic stromal lymphopoietin. The purpose of this review was to discuss the contribution of the epithelium to CRS pathogenesis and to update the field regarding endotypic heterogeneity and various mechanisms for understanding pathogenesis in CRS.
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Affiliation(s)
- Atsushi Kato
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago.
| | - Robert P Schleimer
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago
| | - Benjamin S Bleier
- Department of Otolaryngology-Head & Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston
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Kim DH, Kim SW, Basurrah MA, Hwang SH. Clinical and laboratory features for various criteria of eosinophilic chronic rhinosinusitis: a systematic review and meta-analysis. Clin Exp Otorhinolaryngol 2022; 15:230-246. [PMID: 35413170 PMCID: PMC9441508 DOI: 10.21053/ceo.2022.00052] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/11/2022] [Indexed: 11/22/2022] Open
Abstract
Objectives: To evaluate the differences in clinical and laboratory features between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS and to compare the diagnostic criteria for ECRS.Methods: We compared clinical features and/or laboratory findings classified as ECRS and non-ECRS according to various diagnostic criteria (histological and clinical criteria). In addition, we analyzed studies to compare endoscopic findings, symptom scores, laboratory findings, and computed tomography (CT) findings between ECRS and non-ECRS. Results: Our search included 55 studies with 6,143 patients. As a result of comparing clinical features and/or laboratory criteria with histological criteria, there were no significant differences regarding nasal symptom scores and CT scores according to criteria. Serum eosinophil levels showed differences according to criteria, however, ECRS were higher serum eosinophil levels than non-ECRS in all criteria. In the case of olfactory dysfunction, JESREC and tissue eosinophilia (
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Layhadi JA, Palmer E, Sharif H, Shamji MH. Current Drug Treatments for Allergy. ENCYCLOPEDIA OF RESPIRATORY MEDICINE 2022:477-490. [DOI: 10.1016/b978-0-08-102723-3.00236-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Youn BK, Kim DK, Kim BH, Kim HG, Jeong JH, Cho SH. Local Allergic Inflammation in Chronic Rhinosinusitis With Nasal Polyps Could Influence on Disease Severity and Olfaction. JOURNAL OF RHINOLOGY 2021. [DOI: 10.18787/jr.2021.00363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease resulting from inflammation of the nasal cavity and paranasal sinuses. Systemic allergic inflammation is an important cause of CRSwNP; however, the effect of local allergic inflammation is unclear. This study was designed to investigate the effect of local allergic inflammation in CRSwNP.Materials and Methods: The study included 11 patients with CRSwNP and 18 control subjects. Olfactory function was measured with the Korean Version of Sniffin’s stick test. Nasal lavage fluids (NLFs) were collected from all subjects and analyzed for total IgE, eosinophilic cationic protein (ECP), and cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-4, IL-10, IL-17A, interferon-γ). Flow cytometry was used to measure various inflammatory cells in the NAL fluids.Results: On analysis of flow cytometry and enzyme-linked immunosorbent assay, we found that CRSwNP patients had significantly increased eosinophil (%) and ECP levels in NLFs. In addition, there was significant local-systemic correlation between ECP level in NLFs and blood eosinophils (%) (r=0.391); however, there was no significant association between eosinophils (%) in NLFs and blood eosinophils. Moreover, in CRSwNP patients, the severity of disease was related with blood eosinophil (%), eosinophil (%), and ECP levels in NLFs, whereas olfactory function was associated with blood eosinophil (%) and ECP levels in NLFs.Conclusion: CRSwNP is a disease with high allergic inflammation that has negative impacts on the severity of disease and olfactory function. Therefore, we suggest that control of local allergic inflammation will be helpful to treat CRSwNP patients.
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Chen CL, Wang YT, Yao Y, Pan L, Guo B, Zhu KZ, Ma J, Wang N, Li XL, Deng YK, Liu Z. Inflammatory Endotypes and Tissue Remodeling Features in Antrochoanal Polyps. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2021; 13:863-881. [PMID: 34734505 PMCID: PMC8569026 DOI: 10.4168/aair.2021.13.6.863] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/27/2021] [Accepted: 04/21/2021] [Indexed: 12/03/2022]
Abstract
PURPOSE The pathogenic mechanisms of antrochoanal polyps (ACPs) remain largely unknown. This study aimed to characterize inflammatory patterns and tissue remodeling features in ACPs. METHODS Inflammatory cell infiltration and tissue edema severity as well as fibrin deposition in ACPs and bilateral eosinophilic and noneosinophilic nasal polyps (NPs) were studied with immunohistochemical and immunofluorescence staining. Cytokine levels in sinonasal tissues were detected with the Bio-Plex assay. The expression of coagulation and fibrinolytic markers was measured using reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assays. RESULTS Compared to control tissues and bilateral eosinophilic and noneosinophilic NPs, ACPs had higher levels of neutrophil infiltration and expression of myeloperoxidase (MPO), interleukin (IL)-8 and interferon (IFN)-γ. In total, 94.4% of ACPs demonstrated an eosinophil cationic protein/MPO ratio of < 1, compared to 79.0% of noneosinophilic and 26% of eosinophilic NPs. Principle component and multiple correspondence analyses revealed a neutrophilic and type 1 inflammation pattern in ACPs. Compared to control tissues, edema scores and fibrin deposition were increased, whereas d-dimer and tissue plasminogen activator (tPA) levels were decreased in ACPs and bilateral NPs, with more prominent changes in ACPs even than in eosinophilic NPs. The tPA levels were negatively correlated with IFN-γ, IL-8, and MPO levels in ACPs. Neutrophils were the major cellular source of IFN-γ in ACPs, and the number of IFN-γ+ neutrophils was elevated in ACPs than in control tissues and bilateral eosinophilic and noneosinophilic NPs. CONCLUSIONS ACPs are characterized by the neutrophilic and type 1 inflammation endotype. Neutrophil-derived IFN-γ is associated with reduced tPA production in ACPs.
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Affiliation(s)
- Cai-Ling Chen
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu-Ting Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Pan
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bei Guo
- Department of Otolaryngology-Head and Neck Surgery, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ke-Zhang Zhu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin Ma
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nan Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xue-Li Li
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi-Ke Deng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Vlaminck S, Acke F, Scadding GK, Lambrecht BN, Gevaert P. Pathophysiological and Clinical Aspects of Chronic Rhinosinusitis: Current Concepts. FRONTIERS IN ALLERGY 2021; 2:741788. [PMID: 35387015 PMCID: PMC8974859 DOI: 10.3389/falgy.2021.741788] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/30/2021] [Indexed: 12/01/2022] Open
Abstract
Adult chronic rhinosinusitis (CRS) is a chronic inflammation of the mucosa of the nose and paranasal sinuses. According to the latest EPOS guidelines CRS should be regarded as primary or secondary with distinction between diffuse and localized disease. Further pathophysiologic research identified different inflammatory patterns leading to the term “endotyping of CRS.” The primary focus of endotyping is to define a dominant inflammatory type allowing for better orientation of therapy. The current approach proposes the differentiation between type 2 (eosinophilic) and non-type 2 inflammatory responses. In this review pathophysiological concepts of CRS will be discussed, focusing on the different inflammatory endotypes of T cells with special attention to the eosinophilic type 2 inflammatory response. The contribution of innate and adaptive immune system responses is presented. The possibility of endotyping based on sinonasal secretions sampling is brought to attention because it is indicative of corticosteroid responsiveness and available to most ENT surgeons. Furthermore, the clinical aspects of the three distinct phenotypes are analyzed in view of their characteristics, the related endoscopic findings, typical radiological imaging, histopathology findings, their relation toward allergy and obvious therapeutical implications. This overview will enable clinicians to relate pathophysiological patterns with clinical observations by explaining the different inflammatory mechanisms, hence providing a better understanding of therapy.
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Affiliation(s)
- Stephan Vlaminck
- Department of Otorhinolaryngology, Centre Hospitalier de Mouscron, Mouscron, Belgium
- *Correspondence: Stephan Vlaminck
| | - Frederic Acke
- Department of Otorhinolaryngology, Ghent University/Ghent University Hospital, Ghent, Belgium
| | | | - Bart N. Lambrecht
- Laboratory of Immunoregulation, Flemish Institute for Biotechnology, Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Philippe Gevaert
- Department of Otorhinolaryngology, Ghent University/Ghent University Hospital, Ghent, Belgium
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Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension study. J Allergy Clin Immunol 2021; 149:957-965.e3. [PMID: 34530020 DOI: 10.1016/j.jaci.2021.07.045] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 06/16/2021] [Accepted: 07/13/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently remains uncontrolled despite maximal medical therapy and sinonasal surgery, presenting several unmet needs and challenges. Omalizumab previously demonstrated efficacy in CRSwNP in duplicate phase 3, randomized, placebo-controlled trials (POLYP 1, POLYP 2). OBJECTIVE This open-label extension evaluated the continued efficacy, safety, and durability of response of omalizumab in adults with CRSwNP who completed POLYP 1 or 2. METHODS After 24 weeks of omalizumab or placebo in POLYP 1 and 2, patients (n = 249) received open-label omalizumab plus background nasal mometasone therapy for 28 weeks and were subsequently followed for 24 weeks after omalizumab discontinuation. Efficacy end points assessed change from baseline for the coprimary end points, Nasal Polyp Score and Nasal Congestion Score, and the secondary end points of Sino-Nasal Outcome Test 22, Total Nasal Symptom Score and its components, and University of Pennsylvania Smell Identification Test scores. Safety objectives included incidence of adverse events and adverse events leading to omalizumab discontinuation. RESULTS Patients who continued omalizumab experienced further improvements across coprimary end points and secondary end points through 52 weeks. Patients who switched from placebo to omalizumab experienced favorable responses across end points through week 52 that were similar to POLYP 1 and 2 at week 24. After omalizumab discontinuation, scores gradually worsened over the 24-week follow-up, but remained improved from pretreatment levels for both groups. The safety profile was similar to previous reports. CONCLUSIONS The efficacy and safety profile from this study supports extended omalizumab treatment up to 1 year for CRSwNP with inadequate response to nasal corticosteroids.
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Feng T, Miao P, Liu B, Liu Y, Bao X, Xu J, Ren N, Li Y, Shi J, Cao W, Fang J, Li M, Liu Q, Li J. Sinus Microbiota in Patients With Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis With Nasal Polyps. Front Cell Infect Microbiol 2021; 11:672355. [PMID: 34368010 PMCID: PMC8346020 DOI: 10.3389/fcimb.2021.672355] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 06/04/2021] [Indexed: 12/15/2022] Open
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2-skewed inflammation and increased colonization by Staphylococcus aureus. CRSwNP can be distinguished as eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP) by the infiltration of eosinophils. The local microbiota plays an important role in the persistent inflammation of CRSwNP. To evaluate the bacterial community composition on the distinct types of CRSwNP patients, we collected nasal swabs from 16 ECRSwNP patients, 18 NECRSwNP patients, and 39 healthy control subjects. The microbiome structure for all the samples were analyzed by high-throughput 16S rRNA gene sequencing. Concentration of S. aureus was determined using TaqMan quantitative polymerase chain reaction (qPCR) targeting the nuclease (nuc) gene. The result showed significant differences in the sinus microbiome among healthy control subjects and CRSwNP patients. Microbiota community diversity was significantly lower in NECRSwNP samples compared to that of healthy control subjects. Interestingly, the abundance of several pathogenic bacteria was diverse between ECRSwNP and NECRSwNP patients. Although Staphylococcus prevailed in all groups, the abundance of Staphylococcus was significantly higher in the healthy control group than the ECRSwNP group. More importantly, the abundance of S. aureus was much higher in NECRSwNP patients. This study highlights that microbiota composition may contribute to the different clinical types of CRSwNP, inspiring new therapeutic strategies to resolve this chronic inflammation process.
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Affiliation(s)
- Tingting Feng
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ping Miao
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Bin Liu
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Yao Liu
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ximing Bao
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ji Xu
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Nana Ren
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ying Li
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jiali Shi
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Wanxin Cao
- Department of Otorhinolaryngology, Peking University Third Hospital, Peking University, Beijing, China
| | - Jianchen Fang
- Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Min Li
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Qian Liu
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jiping Li
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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Wang ZC, Yao Y, Chen CL, Guo CL, Ding HX, Song J, Wang ZZ, Wang N, Li XL, Liao B, Yang Y, Yu D, Liu Z. Extrafollicular PD-1 highCXCR5 -CD4 + T cells participate in local immunoglobulin production in nasal polyps. J Allergy Clin Immunol 2021; 149:610-623. [PMID: 34224786 DOI: 10.1016/j.jaci.2021.06.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/01/2021] [Accepted: 06/23/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Local immunoglobulin hyperproduction is observed in nasal polyps (NPs) with and without ectopic lymphoid tissues (eLTs). OBJECTIVE Our aim was to identify the T-cell subsets involved in local immunoglobulin production independent of eLTs in NPs. METHODS The localization, abundance, and phenotype of CD4+ T-cell subsets were studied by immunofluorescence, flow cytometry, and single-cell RNA sequencing. Purified nasal T-cell subsets were cultured with autologous peripheral naive B cells to explore their function. Programmed death ligand 1 and programmed death ligand 2 expression in NPs was investigated by immunofluorescence staining and flow cytometry. RESULTS Accumulation of PD-1highCXCR5-CD4+ T cells outside lymphoid aggregates was found in NPs. Nasal PD-1highCXCR5-CD4+ T cells were characterized by a unique phenotype that was related to B-cell help and tissue residency and distinct from PD-1-/intCXCR5- and CXCR5+ CD4+ T cells in NPs as well as PD-1highCXCR5highCD4+ follicular helper T cells in tonsils. Compared with the frequencies of PD-1highCXCR5-CD4+ T cells and their IFN-γ+, IL-17A+, and IL-21+ subsets in the control inferior turbinate tissues, the frequencies of these cells and their subsets were increased in both eosinophilic and noneosinophilic NPs, whereas the frequencies of the IL-4+ and IL-4+IL-21+ subsets were increased only in eosinophilic NPs. Nasal PD-1highCXCR5-CD4+ T cells induced immunoglobulin production from B cells in a potency comparable to that induced by tonsillar follicular helper T cells. PD-1highCXCR5-CD4+ T-cell frequencies were correlated with IgE levels in eosinophilic NPs. PD-L1 and PD-L2 suppressed the function of PD-1highCXCR5-CD4+ T cells, and their levels were reduced in NPs. PD-1highCXCR5-CD4+ T-cell abundance was associated with the postsurgical relapse of NPs. CONCLUSION PD-1highCXCR5-CD4+ T cells participate in local immunoglobulin production independent of eLTs in NPs.
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Affiliation(s)
- Zhi-Chao Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cai-Ling Chen
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cui-Lian Guo
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong-Xia Ding
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Song
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhe-Zheng Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nan Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xue-Li Li
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Liao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Yang
- The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Di Yu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2021; 20:1-8. [PMID: 31567293 DOI: 10.1097/aci.0000000000000588] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
PURPOSE OF REVIEW Pathogenesis of nasal polyp has been largely studied based on innate and adaptive immunity of sinonasal mucosa. So far, various factors have been identified that trigger an inflammatory response in the pathogenesis of nasal polyps. In this review, we summarized recently updated information in the understanding of mechanisms in the development of chronic rhinosinusitis with nasal polyp (CRSwNP) focusing on Th2 inflammation. RECENT FINDINGS Endotype of CRSwNP presented mainly Th2-skewed inflammation, and it has been associated with refractoriness and comorbidities. Staphylococcus aureus can drive Th2 inflammation by producing enterotoxins and serine protease-like protein. Moreover, S. aureus directly affected mucosal barrier function and enhanced Th2 cytokine production by fast induction of epithelial-derived innate cytokines. Epithelial-derived innate cytokines, including TSLP, IL-25, and IL-33, promote Th2 responses via the development of innate lymphoid cells. Mast cell expresses IL-5, IL-13, and periostin, and it plays a role in the pathogenesis of nasal polyps through orchestrating eosinophil infiltration. Formation of eosinophil extracellular traps and Charcot-Leyden crystals is strongly associated with disease severity and viscous mucus plug production. Therefore, it needs to be investigated mechanistically. The role of neutrophils in Th2 inflammation has been poorly understood but appears to enhance Th2 inflammation and make it more resistant to steroid therapy. SUMMARY There is growing evidence of the role of S. aureus in innate and adaptive immunity, which contribute to Th2 inflammation in CRSwNP. Innate immunity, including epithelial-derived cytokines, plays a crucial role in the development of CRSwNP by inducing various pathways and need to be investigated more as Th2-targeted biomarkers. Recently, the role of neutrophilic inflammation in Th2 inflammation has started to be studied but still remains unclear.
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Wang ZZ, Song J, Wang H, Li JX, Xiao Q, Yu Z, Wang ZC, Liu JX, Pan L, Yao Y, Chen CL, Lu X, Liu C, Gao P, Liu Z. Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps. Allergy 2021; 76:1416-1431. [PMID: 33022771 DOI: 10.1111/all.14612] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 09/06/2020] [Accepted: 09/23/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. OBJECTIVE To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) in eLT formation in NPs. METHODS The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured, and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study. RESULTS The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31- Pdpn+ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1 β2 in NPs with eLTs. CXCL13 upregulated LTα1 β2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 β2 induced expansion of FRCs and CD31+ Pdpn+ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model. CONCLUSION We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα1 β2 in the enlargement of eLTs in NPs.
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Affiliation(s)
- Zhe-Zheng Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Song
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hai Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing-Xian Li
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiao Xiao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ze Yu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi-Chao Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin-Xin Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Pan
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cai-Ling Chen
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Lu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chaohong Liu
- Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China
| | - Peisong Gao
- Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Comparative analysis of inflammatory signature profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyposis. Biosci Rep 2021; 40:222068. [PMID: 32039442 PMCID: PMC7040463 DOI: 10.1042/bsr20193101] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 01/18/2020] [Accepted: 01/24/2020] [Indexed: 12/13/2022] Open
Abstract
Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents a heterogeneous disorder that can be classified into either eosinophilic or noneosinophilic endotypes. However, the immunological mechanisms of each remain unclear. The purpose of the present study was to compare and analyze inflammatory signatures of eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). Cytokine antibody array was used to identify inflammatory mediators that were differentially expressed among ECRSwNP, NECRSwNP, and control groups. Then, bioinformatics approaches were conducted to explore biological functions and signaling pathways. In addition, pairwise correlation analyses were performed among differential levels of inflammatory mediators and tissue eosinophil infiltration. The results showed that nine mediators were significantly up-regulated in ECRSwNP, including eotaxin-2, eotaxin-3, CCL18, IL-4, IL-5, IL-10, IL-12p70, IL-13, and IL-15. Bioinformatics analysis indicated that these mediators were mainly enriched in leukocyte chemotaxis and proliferation, JAK-STAT cascade, asthma, and Th1 and Th2 cell differentiation. Furthermore, seven mediators were identified to be significantly up-regulated in NECRSwNP, including CCL20, resistin, transforming growth factor (TGF)-β2, triggering receptor expressed on myeloid cells 1 (TREM-1), CD14, glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), and lipocalin-2. These mediators were closely associated with LPS responses, neutrophil chemotaxis and migration, and IL-17 signaling pathway. In addition, pairwise correlation analyses indicated that differential levels of inflammatory mediators in ECRSwNP and NECRSwNP were broadly correlated with each other and with tissue eosinophil infiltration. In conclusion, we found that ECRSwNP and NECRSwNP exhibited different patterns of inflammatory signatures. These findings may provide further insights into heterogeneity of CRSwNP.
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Formation of nasal polyps: The roles of innate type 2 inflammation and deposition of fibrin. J Allergy Clin Immunol 2020; 145:740-750. [PMID: 32145873 DOI: 10.1016/j.jaci.2020.01.027] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/22/2020] [Accepted: 01/24/2020] [Indexed: 12/28/2022]
Abstract
Chronic rhinosinusitis (CRS) is one of the most common chronic diseases worldwide. It is a heterogeneous disease, and geographical or ethnic differences in inflammatory pattern in nasal mucosa are major issues. Tissue eosinophilia in CRS is highly associated with extensive sinus disease, recalcitrance, and a higher nasal polyp (NP) recurrence rate after surgery. The prevalence of eosinophilic CRS (ECRS) is increasing in Asian countries within the last 2 decades, and this trend appears to be occurring across the world. International consensus criteria for ECRS are required for the accurate understanding of disease pathology and precision medicine. In a multicenter large-scale epidemiological survey, the "Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study," ECRS was definitively defined when the eosinophil count in nasal mucosa is greater than or equal to 70 eosinophils/hpf (magnification, ×400), and this study proposed an algorithm that classifies CRS into 4 groups according to disease severity. The main therapeutic goal with ECRS is to eliminate or diminish the bulk of NP tissue. NPs are unique abnormal lesions that grow from the lining of the nasal and paranasal sinuses, and type 2 inflammation plays a critical role in NP development in patients with ECRS. An imbalance between protease and endogenous protease inhibitors might play a pivotal role in the initiation and exacerbation of type 2 inflammation in ECRS. Intraepithelial mast cells in NPs, showing a tryptase+, chymase- phenotype, may also enhance type 2 inflammation. Intense edema and reduced fibrosis are important histological features of eosinophilic NPs. Mucosal edema mainly consists of exuded plasma protein, and excessive fibrin deposition would be expected to contribute to the retention of proteins from capillaries and thereby perpetuate mucosal edema that may play an etiological role in NPs. Upregulation of the coagulation cascade and downregulation of fibrinolysis strongly induce abnormal fibrin deposition in nasal mucosa, and type 2 inflammation plays a central role in the imbalance of coagulation and fibrinolysis.
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Kong H, He J, Guo S, Song Q, Xiang D, Tao R, Yu H, Chen G, Huang Z, Ning Q, Huang J. Endothelin receptors promote schistosomiasis-induced hepatic fibrosis via splenic B cells. PLoS Pathog 2020; 16:e1008947. [PMID: 33075079 PMCID: PMC7595619 DOI: 10.1371/journal.ppat.1008947] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 10/29/2020] [Accepted: 08/31/2020] [Indexed: 12/17/2022] Open
Abstract
Endothelin receptors (ETRs) are activated by vasoactive peptide endothelins and involved in the pathogenesis of hepatic fibrosis. However, less is known about the role of ETRs in Schistosoma (S.) japonicum-induced hepatic fibrosis. Here, we show that the expression of ETRs is markedly enhanced in the liver and spleen tissues of patients with schistosome-induced fibrosis, as well as in murine models. Additional analyses have indicated that the expression levels of ETRs in schistosomiasis patients are highly correlated with the portal vein and spleen thickness diameter, both of which represent the severity of fibrosis. Splenomegaly is a characteristic symptom of schistosome infection, and splenic abnormality may promote the progression of hepatic fibrosis. We further demonstrate that elevated levels of ETRs are predominantly expressed on splenic B cells in spleen tissues during infection. Importantly, using a well-studied model of human schistosomiasis, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells characterized by interleukin-10 (IL-10) secretion and regulatory T (Treg) cell-inducing capacity. Our study provides insights into the mechanisms by which ETRs regulate schistosomiasis hepatic fibrosis and highlights the potential of endothelin receptor antagonist as a therapeutic intervention for fibrotic diseases. Schistosomiasis is a serious but neglected tropical infectious disease. which can lead to hepatic fibrosis and death. To date, there are still no approved antifibrotic therapies. Hepatic fibrosis results in portal hypertension and variceal bleeding, and it is the primary cause of mortality from schistosomiasis. Splenomegaly and hypersplenism can manifest following the development of portal hypertension. Accumulating evidence suggests that the spleen plays a critical role in the development of hepatic fibrosis. In this study, using Schistosoma (S.) japonicum in both humans and mice, we show that progressive hepatic schistosomiasis caused elevation of endothelin receptors (ETRs) both in liver and spleen tissues, and the endothelin receptor-producing cells are mainly located in splenic B cells. More importantly, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells during infection. Thus, our study highlights the potential of endothelin receptor antagonist as a therapeutic intervention for schistosomiasis and other fibrotic diseases.
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Affiliation(s)
- Hongyan Kong
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinan He
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shusen Guo
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiqin Song
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dandan Xiang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ran Tao
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haijing Yu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guang Chen
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiaquan Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- * E-mail:
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孙 立, 朱 冬, 孟 粹. [The study and clinical application of the endotypes of chronic rhinosinusitis]. LIN CHUANG ER BI YAN HOU TOU JING WAI KE ZA ZHI = JOURNAL OF CLINICAL OTORHINOLARYNGOLOGY, HEAD, AND NECK SURGERY 2020; 34:765-768. [PMID: 32842216 PMCID: PMC10127916 DOI: 10.13201/j.issn.2096-7993.2020.08.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Indexed: 11/12/2022]
Abstract
Chronic rhinosinusitis （CRS） is a heterogeneous inflammatory disease with an as-yet-undefined etiology. In contrast to the phenotypic classification of chronic rhinosinusitis, endotype classification is based on its underlying pathophysiological mechanisms. Endotypes of CRS can provide information on the risk of disease progression, recurrence and comorbidities, as well as identify appropriate therapeutic targets to further guide the precise treatment of CRS. This article classifies the endotypes of CRS based on cytokines, cell composition, IgE and CysLT, and outlines the clinical application of several targeted therapeutic biologics.
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Affiliation(s)
- 立薇 孙
- 吉林大学中日联谊医院耳鼻咽喉头颈外科(长春, 130033)
| | - 冬冬 朱
- 吉林大学中日联谊医院耳鼻咽喉头颈外科(长春, 130033)
- 吉林省上气道过敏性疾病精准诊疗实验室
| | - 粹达 孟
- 吉林大学中日联谊医院耳鼻咽喉头颈外科(长春, 130033)
- 吉林省上气道过敏性疾病精准诊疗实验室
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Chronic Rhinosinusitis and Allergy: Increased Allergen Sensitization Versus Real Allergic Rhinitis Multimorbidity: a Systematic Review. Curr Allergy Asthma Rep 2020; 20:19. [PMID: 32430789 DOI: 10.1007/s11882-020-00913-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW The objective of this article is to provide a recent update of the association between allergic inflammation and chronic rhinosinusitis. The systematic approach of this review article critically evaluates the literature published over the past few years and summarizes the specific pathophysiologic pathway of chronic sinonasal inflammation that has been postulated. RECENT FINDINGS From a systematic search of the Ovid Medline and Embase, 11 studies were included in a qualitative analysis of the association between systemic allergy and chronic rhinosinusitis (CRS). Of the 11 studies, four showed an association, three were inconclusive, and four did not show any association. From the systematic search, 50 studies suggested four possible pathophysiologic pathways that may explain the association of allergic inflammation and CRS, namely, (1) staphylococcal enterotoxin, (2) the innate immunity pathway, (3) mast cell-associated inflammation, and (4) dysbiosis of microbiota. The association of systematic allergy and CRS remains inconclusive. The recent advances in the study of the pathophysiologic pathway of CRS may lead to the possibility of a targeted treatment option for CRS.
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Aazami H, Seif F, Ghalehbaghi B, Babaheidarian P, Mohebbi A, Ahmadi A, Khoshmirsafa M, Ghalehbaghi S, Behnam B, Entezami KZ, Madjd Z, Falak R. Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients. Allergy Asthma Clin Immunol 2020; 16:30. [PMID: 32351585 PMCID: PMC7183627 DOI: 10.1186/s13223-020-00428-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 04/15/2020] [Indexed: 01/21/2023] Open
Abstract
Background Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. Methods Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. Results We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-β was significantly elevated in the sinonasal tissue of patients with CRSsNP. Conclusions Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.![]()
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Affiliation(s)
- Hossein Aazami
- 1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Seif
- 2Department of Immunology and Allergy, Academic Center for Education, Culture and Research, Tehran, Iran.,3Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Babak Ghalehbaghi
- 4ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Pegah Babaheidarian
- 5Department of Pathology, Rasoul Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Mohebbi
- 4ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Aslan Ahmadi
- 4ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Khoshmirsafa
- 1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,6Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Sahand Ghalehbaghi
- 4ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Babak Behnam
- 7Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Kobra Zinat Entezami
- 1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Madjd
- 8Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Falak
- 1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,6Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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McHugh T, Levin M, Snidvongs K, Banglawala SM, Sommer DD. Comorbidities associated with eosinophilic chronic rhinosinusitis: A systematic review and meta-analysis. Clin Otolaryngol 2020; 45:574-583. [PMID: 32243094 DOI: 10.1111/coa.13536] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 03/09/2020] [Accepted: 03/22/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Eosinophilic chronic rhinosinusitis (ECRS) is a histological subtype of CRS that is generally recognised as being more difficult to manage. Patients with ECRS tend to have greater disease severity and poorer treatment outcomes after sinus surgery when compared with non-ECRS patients. The histopathology and biomarker assessments of ECRS are often unavailable prior to surgery and may be impractical and costly to analyse. Thus, the primary objective of this study was to understand clinical comorbidities associated with ECRS. DESIGN/SETTING We searched three independent databases for articles that reported clinical CRS comorbidities associated with tissue eosinophilia. Data from studies with the same reported comorbidities were pooled, and a forest plot analysis was used to assess potential associations with four different conditions including allergic rhinitis, ASA sensitivity, asthma and atopy. The association between the phenotype of nasal polyps and ECRS was also quantified as a secondary objective. ECRS cut-off levels were as defined by papers included. MAIN OUTCOME/RESULTS Eighteen articles were identified. The presence of nasal polyps (the first numbers in brackets represent odds ratios) (5.85, 95% CI [3.61, 9.49], P < .00001), ASA sensitivity (5.63, 95% CI [3.43, 9.23], P < .00001), allergic rhinitis (1.84, 95% CI [1.27, 2.67], P = .001) and asthma (3.15, 95% CI [2.61, 3.82], P < .00001) were found to be significantly associated with tissue eosinophilia. Atopy, however, was not significantly associated with tissue eosinophilia (1.71, 95% CI [0.59, 4.95], P = .32). CONCLUSION Certain clinical disease characteristics such as ASA sensitivity, allergic rhinitis and asthma are more associated with CRS patients with eosinophilia when compared to those without eosinophilia. The phenotype of nasal polyps was also associated with ECRS. It is important for surgeons to recognise these comorbidities to ensure correct diagnoses, management and follow-up are implemented.
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Affiliation(s)
- Tobial McHugh
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Marc Levin
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Kornkiat Snidvongs
- Division of Otolaryngology, Head and Neck Surgery, Chulalongkorn University, Bangkok, Thailand
| | - Sarfaraz M Banglawala
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Doron D Sommer
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
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Nasal cytology with emphasis on mast cells can improve the diagnosis and treatment of chronic rhinosinusitis. Chin Med J (Engl) 2020; 132:2237-2241. [PMID: 31425355 PMCID: PMC6797148 DOI: 10.1097/cm9.0000000000000387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Objective: Chronic rhinosinusitis (CRS) involves inflammation of the nasal and para-nasal mucosa. Due to its heterogeneous nature, unknown pathogenesis, and high recurrence rate, effective treatment is difficult. Nasal cytology is presently not a part of the routine diagnosis or treatment decision for CRS. Data sources: A literature search was performed for published papers in English between January 1990 and June 2019 using MEDLINE. Study selection: Terms used were chronic rhinosinusitis, eosinophils, etiology, immunopathology, inflammation, mast cells, nasal cytology, polyps, and treatment. Both reviews and original articles were collected and studied. Results: There is no standard nasal fluid, mucus sampling, or staining techniques for identifying inflammatory cell types. Results were divergent from different countries. Moreover, the main focus of these papers on the cells in nasal washings was eosinophils, with infrequent mentioning of other cell types that may imply different etiology and pathology. The heterogeneous cell profile of CRS and the role of mast cells have been unappreciated due to the lack of specific immunohistochemical technique or study of its unique mediators. Conclusions: Nasal cytology could help distinguish the type and the activation state of inflammatory cells. Thus it can help in providing a clearer picture of CRS pathogenesis, identifying different patient groups, and developing effective treatments.
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Liu Z, Chen J, Cheng L, Li H, Liu S, Lou H, Shi J, Sun Y, Wang D, Wang C, Wang X, Wei Y, Wen W, Yang P, Yang Q, Zhang G, Zhang Y, Zhao C, Zhu D, Zhu L, Chen F, Dong Y, Fu Q, Li J, Li Y, Liu C, Liu F, Lu M, Meng Y, Sha J, She W, Shi L, Wang K, Xue J, Yang L, Yin M, Zhang L, Zheng M, Zhou B, Zhang L. Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2020; 12:176-237. [PMID: 32009319 PMCID: PMC6997287 DOI: 10.4168/aair.2020.12.2.176] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 11/05/2019] [Accepted: 11/13/2019] [Indexed: 02/05/2023]
Abstract
The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines-with a focus on China-will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
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Affiliation(s)
- Zheng Liu
- Department of Otolaryngology Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianjun Chen
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Cheng
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
- International Centre for Allergy Research, Nanjing Medical University, Nanjing, China
| | - Huabin Li
- Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Shixi Liu
- Department of Otolaryngology, West China Hospital, Sichuan University, Chengdu, China
| | - Hongfei Lou
- 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
| | - Jianbo Shi
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ying Sun
- Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Dehui Wang
- Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Chengshuo Wang
- 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
| | - Xiangdong Wang
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Yongxiang Wei
- Department of Otolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Weiping Wen
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Otorhinolaryngology Hospital, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pingchang Yang
- Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China
| | - Qintai Yang
- Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Gehua Zhang
- Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuan Zhang
- 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
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Changqing Zhao
- Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Shanxi Medical University, Taiyuan, China
| | - Dongdong Zhu
- Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Li Zhu
- Department of Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, China
| | - Fenghong Chen
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Dong
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Qingling Fu
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingyun Li
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Yanqing Li
- Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Chengyao Liu
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Feng Liu
- Department of Otolaryngology, West China Hospital, Sichuan University, Chengdu, China
| | - Meiping Lu
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Yifan Meng
- 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
| | - Jichao Sha
- Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Wenyu She
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Lili Shi
- Department of Otolaryngology Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kuiji Wang
- 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
| | - Jinmei Xue
- Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Shanxi Medical University, Taiyuan, China
| | - Luoying Yang
- Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Min Yin
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
- International Centre for Allergy Research, Nanjing Medical University, Nanjing, China
| | - Lichuan Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ming Zheng
- 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
| | - Bing Zhou
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
| | - Luo Zhang
- 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
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
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Biologics for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 2020; 145:725-739. [DOI: 10.1016/j.jaci.2020.01.020] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 12/14/2022]
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Staudacher AG, Peters AT, Kato A, Stevens WW. Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis. Ann Allergy Asthma Immunol 2020; 124:318-325. [PMID: 32007571 DOI: 10.1016/j.anai.2020.01.013] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 01/10/2020] [Accepted: 01/22/2020] [Indexed: 01/17/2023]
Abstract
OBJECTIVE With the advent of new treatment options for Chronic Rhinosinusitis (CRS) comes the ability for physicians to provide more individualized patient care. Physicians are now tasked with identifying who may be the best candidate for a particular therapy. In this review, existing biomarkers and potentially new methods that could guide treatment choices in CRS patients will be discussed. DATA SOURCES Published literature obtained through PubMed searches. STUDY SELECTION Studies relevant to inflammatory endotypes, phenotypes, and biomarkers in CRS were included. RESULTS Currently, there are no clinically validated tools that determine the best therapeutic modality for CRS patients with or without nasal polyps (CRSwNP or CRSsNP). Patients with CRS can be classified into three endotypes based on the presence of type 1, type 2, or type 3 inflammation. CRS endotypes can be influenced by age and geographic location. Clinical application however may be limited since endotyping current requires basic research laboratory support. Clinical symptoms may also predict inflammatory endotypes with smell loss being indicative of type 2 inflammation. Numbers of tissue and/or peripheral eosinophils as well as levels of IgE may predict disease severity in CRSwNP but not necessarily treatment responses. Unique clinical phenotypes or biomarkers are especially lacking that predict type 1 or type 3 inflammation in CRSwNP or type 1, type 2, or type 3 inflammation in CRSsNP. CONCLUSION While significant progress has been made in characterizing endotypes, phenotypes, and biomarkers in CRS, additional studies are needed to determine if and how these factors could assist physicians in providing more individualized clinical care.
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Affiliation(s)
- Anna G Staudacher
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Anju T Peters
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Atsushi Kato
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Whitney W Stevens
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
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45
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Wang F, Yang Y, You Q, Chen H. Prognostic Significance of Serum Complement Component 3 in Chronic Rhinosinusitis with Nasal Polyps. ORL J Otorhinolaryngol Relat Spec 2020; 82:67-73. [PMID: 31935724 DOI: 10.1159/000504195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 10/17/2019] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The aim of this study was to assess the relationship between serum complement component 3 (C3) levels and disease recurrences in patients with chronic rhinosinusitis with nasal polyps (NPs). METHODS Ninety-seven patients with NPs and 30 controls were recruited. Clinical features were collected. Serum concentrations of C3 and C4 were measured before and after endoscopic sinus surgery. RESULTS Compared to the controls, increased C3 levels were found in patients with NPs. Patients with polyp recurrences had higher pre- and postoperative serum C3 levels than patients without polyp recurrences. Serum C3 levels dropped after surgery. After polyp regrowth, the mean C3 level in the recurrent group elevated again to the degree similar to that before surgery. When patients were stratified by tissue eosinophilia, no significant difference was seen in pre-/postoperative, absolute change after surgery, and post-recurrent C3 levels between patients without and with eosinophilic NPs in the group with disease recurrences. CONCLUSION Serum C3 may be involved in the pathogenesis of NPs. Higher serum C3 levels may pinpoint patients at high risk of recurrence as an independent factor. Furthermore, the change in C3 levels after surgery may have the potential to serve as a predictor for polyp progression. Adding serum C3 measurement to the routine walk-up in the clinical management of NPs is worth further investigation and may help physicians make a more rational diagnostic and/or therapeutic decision regarding this disease.
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Affiliation(s)
- Feng Wang
- Department of Otolaryngology, The First Affiliated Hospital, School of Medicine, ZheJiang University, Hangzhou, China,
| | - Yang Yang
- Department of Otolaryngology, The First Affiliated Hospital, School of Medicine, ZheJiang University, Hangzhou, China
| | - Qihan You
- Department of Pathology, The First Affiliated Hospital, School of Medicine, ZheJiang University, Hangzhou, China
| | - Haihong Chen
- Department of Otolaryngology, The First Affiliated Hospital, School of Medicine, ZheJiang University, Hangzhou, China
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46
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Enache I, IoniȚĂ E, Mitroi M, Anghelina F, MogoantĂ C, Ciolofan S, CĂpitĂnescu A, Stepan A, Simionescu C. Histopathological Features of Chronic Rhinosinusitis with Nasal Allergic Polyps. CURRENT HEALTH SCIENCES JOURNAL 2020; 46:66-71. [PMID: 32637167 PMCID: PMC7323723 DOI: 10.12865/chsj.46.01.09] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 12/26/2019] [Indexed: 11/18/2022]
Abstract
Chronic rhinosinusitis with nasal polyps of allergic etiology is one of the most common pathology in the ENT sphere that affect a significant percentage of population. The paper aims to establish the involvement of the allergic component in the genesis of nasal polyposis. The study included 150 nasal polyps from patients hospitalized and operated in the ENT Department of Craiova's Clinical Emergency County Hospital. The biological material was fixed in 10% buffered formalin, processed by classical paraffin embedding technique followed by hematoxylin-eosin staining and it was interpreted in the Pathology Department of the same hospital. We evaluated a number of histopathological parameters that were given severity scores. The most common changes at epithelial level were: basal layer hyperplasia observed in 87 cases (58%), goblet cell hyperplasia in 121 cases (80.66%), basal membrane thickening with values between 10-42μm corresponding to a number of 118 cases (78.66%). The most important stromal changes were edema in 88% and infiltration with eosinophils 100%, indicating the allergic nature of this disease.
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Affiliation(s)
- Irina Enache
- PhD student, Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Elena IoniȚĂ
- Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Mihaela Mitroi
- Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Florin Anghelina
- Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Carmen MogoantĂ
- Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Sorin Ciolofan
- Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Alina CĂpitĂnescu
- Department of ENT, University of Medicine and Pharmacy of Craiova, Romania
| | - Alex Stepan
- Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania
| | - Cristiana Simionescu
- Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania
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Ren X, Dong F, Zhuang Y, Wang Y, Ma W. Effect of neuromedin U on allergic airway inflammation in an asthma model. Exp Ther Med 2019; 19:809-816. [PMID: 32010240 PMCID: PMC6966147 DOI: 10.3892/etm.2019.8283] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022] Open
Abstract
Asthma is a major inflammatory airway disease with high incidence and mortality rates. The Global Initiative for Asthma released a report called ‘The Global Burden of Asthma’ in 2004. However, the specific pathogenesis of asthma remains unclear. An increasing number of studies have demonstrated that neuromedin U (NMU) plays a pleiotropic role in the pathogenesis of asthma. NMU is a highly structurally conserved neuropeptide that was first purified from porcine spinal cord and named for its contractile effect on the rat uterus. NMU amplifies type 2 innate lymphoid cell (ILC2)-driven allergic lung inflammation. The NMU receptors (NMURs), designated as NMUR1 and NMUR2, belong to the G protein-coupled receptor family. NMUR1 has also been found in immune cells, including ILC2s, mast cells and eosinophils. In view of the important roles of NMU in the pathogenesis of asthma, the present review evaluates the potential mechanisms underlying the impact of NMU on asthma and its association with asthma therapy.
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Affiliation(s)
- Xiaojie Ren
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Anaesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Fang Dong
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Anaesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Yuerong Zhuang
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Anaesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Yong Wang
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Anaesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Wuhua Ma
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Anaesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
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Wang H, Pan L, Liu Z. Neutrophils as a Protagonist and Target in Chronic Rhinosinusitis. Clin Exp Otorhinolaryngol 2019; 12:337-347. [PMID: 31394895 PMCID: PMC6787473 DOI: 10.21053/ceo.2019.00654] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 06/28/2019] [Indexed: 12/13/2022] Open
Abstract
Neutrophils have traditionally been acknowledged as the first immune cells that are recruited to inflamed tissues during acute inflammation. By contrast, their importance in the context of chronic inflammation has been studied in less depth. Neutrophils can be recruited and are largely present in the nasal mucosa of patients with chronic rhinosinusitis (CRS) both in Asians and in Caucasians. Increased infiltration of neutrophils in patients with CRS has been linked to poor corticosteroid response and disease prognosis. Meanwhile, tissue neutrophils may possess specific phenotypic features distinguishing them from resting blood counterparts and are endowed with particular functions, such as cytokines and chemokines production, thus may contribute to the pathogenesis of CRS. This review aims to summarize our current understanding of the pathophysiologic mechanisms of CRS, with a focus on the roles of neutrophils. We discuss recruitment, function, and regulation of neutrophils in CRS and outline the potential therapeutic strategies targeting neutrophils.
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Affiliation(s)
- Hai Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Pan
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Role of allergen-specific T-follicular helper cells in immunotherapy. Curr Opin Allergy Clin Immunol 2019; 18:495-501. [PMID: 30124489 DOI: 10.1097/aci.0000000000000480] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW The discovery of novel T-cell subsets including follicular helper T (Tfh) cells has broadened our knowledge on the complex immune networks in allergic diseases. This review summarizes the evidence for Tfh cells in controlling immune responses to allergens with a particular focus on immunoglobulin E (IgE) production and discusses the implication of such regulation in allergen-specific immunotherapy. RECENT FINDINGS Tfh cells support the production of IgE in animal models for allergic diseases. Among Tfh cells, the type 2 subset (Tfh2) is considered as the major player that secretes IL-4 and promotes the isotype switching to IgE. In human inflammatory airway diseases, including allergic rhinitis, asthma, and nasal polyps, the increased frequencies of circulating or tissue Tfh2 cells have been reported. Notably, the frequencies of Dermatophagoides pteronyssinus group 1 (Der p 1)-specific IL-4 Tfh cells in blood positively correlated with serum Der p-specific IgE levels in allergic rhinitis patients. After allergen immunotherapy (AIT), Der p 1-specific IL-4 Tfh cells declined in allergic rhinitis patients, which associated with the remission of clinical symptoms. SUMMARY Allergen-specific IL-4 Tfh cells contribute to the production of allergen-specific IgE and correlate with clinical efficacy of AIT in allergic rhinitis patients, which suggest allergen-specific Tfh cells as a promising therapeutic target and biomarker for AIT in allergic rhinitis.
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Zheng H, Tang L, Song B, Yang X, Chu P, Han S, Wang P, Lu J, Ge W, Ni X. Inflammatory patterns of antrochoanal polyps in the pediatric age group. Allergy Asthma Clin Immunol 2019; 15:39. [PMID: 31249603 PMCID: PMC6585040 DOI: 10.1186/s13223-019-0352-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 06/13/2019] [Indexed: 11/27/2022] Open
Abstract
Background The pathogenesis and etiology of antrochoanal polyps (ACPs) remains obscure. This study aimed to characterize the inflammatory profiles and investigate the effect of atopy on the pathogenesis of pediatric ACPs. Methods Thirty-three ACP patients and ten control subjects were enrolled from January to December 2017. The severity of individual nasal symptoms was scored on a visual analogue scale (VAS). The serum total immunoglobulin E (IgE) and cytokines level was measured by multiplexed luminex assay. Results There was no significant difference in VAS scores and counts of inflammatory cells between atopic and nonatopic ACP. No difference in IFNγ, IL-4, IL-5, IL-13, IL-17A and IL-25 was found between control and whole ACP, nonatopic and atopic ACP. Significantly increased levels of IL-6 and IL-10 were found in ACP compared with control. For neutrophil chemotactic factor, significant increases of IL-8 and GRO were observed in ACP, but for eosinophil chemotactic factor, no difference was found in RANTES and GM-CSF. IL-6 level was positively correlated with IL-8, MCP1, and GRO level, and IL-10 level was positively correlated with IL-4 and IL-13 in ACP subjects. Conclusion Nasal obstruction was the most common symptom in ACPs in children. Allergic condition may have a poor role in the pathogenesis of ACPs. IL-6 plays a crucial role in the pathogenesis of neutrophilic inflammation in patients with ACPs and may provide a new treatment strategy for ACPs in children. Treg cell associated cytokine IL-10 was involved in the inflammatory pathophysiological process of ACPs and played a certain regulatory role.
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Affiliation(s)
- Huiwen Zheng
- 1Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Lixing Tang
- 2Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Beibei Song
- 2Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Xiaojian Yang
- 2Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Ping Chu
- 1Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Shujing Han
- 1Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Pengpeng Wang
- 2Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Jie Lu
- 1Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Wentong Ge
- 1Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.,2Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Xin Ni
- 1Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.,2Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China
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