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Solé D, Kuschnir FC, Pastorino AC, Constantino CF, Galvão C, Chong E Silva DC, Baptistella E, Goudouris ES, Sakano E, Ejzenbaum F, Matsumoto FY, Mizoguchi FM, Aarestrup FM, Wandalsen GF, Chong Neto HJ, Brito de Oliveira JV, Lubianca Neto JF, Rizzo MCV, Silva Chavarria MLF, Urrutia-Pereira M, Filho NAR, de Paula Motta Rubini N, Mion O, Piltcher OB, Ramos RT, Francesco RD, Roithmann R, Anselmo-Lima WT, Romano FR, de Mello Júnior JF. V Brazilian Consensus on Rhinitis - 2024. Braz J Otorhinolaryngol 2025; 91:101500. [PMID: 39388827 PMCID: PMC11497470 DOI: 10.1016/j.bjorl.2024.101500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 08/17/2024] [Indexed: 10/12/2024] Open
Abstract
Since we published the "IV Brazilian Consensus on Rhinitis", in2017, several advances have been achieved and have enabled a further understanding of the different aspects of "Rhinitis". This new guideline, developed jointly by ASBAI, SBP and SBORL, represents a relevant milestone in the updated and integrated management of the different forms of the disease, and it aims to unify evidence-based approaches to improve the diagnosis and treatment of this common and often underestimated condition. The document covers a wide range of topics, including clear definitions of the different phenotypes and endotypes of rhinitis, risk factors, updated diagnostic criteria, and recommended methods for clinical and laboratory investigation. We stress the importance of detailed clinical history and objective assessment, as well as tools for control and assessing severity tools an accurate diagnostic approach to the disease. Regarding treatment, it emphasizes the treatment customization, considering the severity of symptoms, the presence of comorbidities and the impact on the patient's quality of life. We discuss different drug treatment, in addition to non-pharmacological measures, such as environmental control and specific immunotherapy; and the possible role of immunobiological agents. Furthermore, the consensus addresses issues related to patient education, prevention and management of special situations, such as rhinitis in children, in pregnant women and in the elderly. In short, the "V Brazilian Consensus on Rhinitis" represents a comprehensive and updated guide for healthcare professionals involved in the diagnosis and management of rhinitis, aiming to improve patients' quality of life through an integrated and evidence-based approach.
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Affiliation(s)
- Dirceu Solé
- Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil; Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil
| | - Fábio Chigres Kuschnir
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Antônio Carlos Pastorino
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade de São Paulo, São Paulo, SP, Brazil
| | - Clóvis F Constantino
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade de Santo Amaro, São Paulo, SP, Brazil
| | - Clóvis Galvão
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade de São Paulo, São Paulo, SP, Brazil
| | - Débora Carla Chong E Silva
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade Federal do Paraná́, Curitiba, PR, Brazil
| | - Eduardo Baptistella
- Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil
| | - Ekaterini Simões Goudouris
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Eulália Sakano
- Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil; Universidade Estadual de Campinas, Campinas, SP, Brazil
| | - Fábio Ejzenbaum
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil
| | - Fausto Yoshio Matsumoto
- Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil; Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil
| | - Flavio Massao Mizoguchi
- Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil
| | - Fernando Monteiro Aarestrup
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil
| | - Gustavo F Wandalsen
- Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil; Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil
| | - Herberto José Chong Neto
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade Federal do Paraná́, Curitiba, PR, Brazil
| | | | - José Faibes Lubianca Neto
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Fundação Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | | | | | - Marilyn Urrutia-Pereira
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal do Pampa, Uruguaiana, RS, Brazil
| | - Nelson Augusto Rosário Filho
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal do Paraná́, Curitiba, PR, Brazil
| | - Norma de Paula Motta Rubini
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Olavo Mion
- Universidade de São Paulo, São Paulo, SP, Brazil; Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil
| | - Otávio Bejzman Piltcher
- Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazi
| | - Regina Terse Ramos
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Renata Di Francesco
- Sociedade Brasileira de Pediatria, Rio de Janeiro, RJ, Brazil; Universidade de São Paulo, São Paulo, SP, Brazil
| | - Renato Roithmann
- Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil; Universidade Luterana do Brasil, Canos, RS, Brazil
| | - Wilma Terezinha Anselmo-Lima
- Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil; Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | - Fabrizio Ricci Romano
- Universidade de São Paulo, São Paulo, SP, Brazil; Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil
| | - João Ferreira de Mello Júnior
- Universidade de São Paulo, São Paulo, SP, Brazil; Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, São Paulo, SP, Brazil.
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Mühlmeier G, Tisch M. [Immunoglobulin E in nasal secretions]. HNO 2024; 72:633-638. [PMID: 39031180 DOI: 10.1007/s00106-024-01499-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 07/22/2024]
Abstract
Diagnosis of allergic disease is primarily verified by IgE blood serum analysis. Determination in nasal secretions is technically more difficult, particularly due to a low specimen volume and the method of sample collection. Nasal secretions are frequently collected by lavage, which allows qualitative diagnostics, whereas swabs with defined amounts of mucus enable quantitative analyses. In the case of negative skin and serum tests, detection of IgE in nasal mucus combined with nasal provocation testing aids differentiation between local allergic and nonallergic rhinitis.
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Affiliation(s)
- Guido Mühlmeier
- Klinik für Hals-Nasen-Ohren-Heilkunde, Kopf- und Halschirurgie, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Deutschland.
| | - Matthias Tisch
- Klinik für Hals-Nasen-Ohren-Heilkunde, Kopf- und Halschirurgie, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Deutschland
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Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study. J Pers Med 2022; 12:jpm12071179. [PMID: 35887676 PMCID: PMC9322075 DOI: 10.3390/jpm12071179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/13/2022] [Accepted: 07/19/2022] [Indexed: 11/25/2022] Open
Abstract
Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. Methods: Thirty-one patients (age 18–64 years) receive intranasal (mometasone furoate, 200 µg b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin’ sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.
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Clinical Evidence of Type 2 Inflammation in Non-allergic Rhinitis with Eosinophilia Syndrome: a Systematic Review. Curr Allergy Asthma Rep 2022; 22:29-42. [PMID: 35141844 DOI: 10.1007/s11882-022-01027-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2021] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW Non-allergic rhinitis (NAR) includes different subtypes, among which NAR with eosinophilia syndrome (NARES) is the most important because of severity of symptoms and the high risk of comorbidities. Its pathophysiology is still object of debate, but a crucial role of chronic eosinophilic inflammation has been recognized. The aim of this review is to critically analyze the current evidence regarding the hypothesis that NARES may be considered a type 2 inflammatory disorder. RECENT FINDINGS The definition and diagnostic criteria for NARES are not universally shared and adopted, thus generating difficulties in reproducing the results. At present, there is extreme heterogeneity in sampling methods and disagreement in the cut-off of local eosinophilic count to determine a diagnosis of NARES. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was applied to identify English-language experimental and clinical articles regarding NARES. The search was performed in April 2021. Twenty-six articles were included. Our data suggest a particular heterogeneity regarding sampling and specific cut-offs adopted for diagnosis of NARES and consensus should be reached. We suggest that eosinophil count should be reported as an absolute value for at least 10 observed rich fields in order to increase the level of standardization. Consensus among authors on this topic should be reached with particular attention to the cut-off for diagnosis. In the future, this limitation may be overcome by the identification of repeatable biomarkers to refine diagnosis and prognosis of NARES. Furthermore, our data strongly suggest that NARES have numerous similarities with clinical features of the most common type 2 diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP): late onset, association with type 2 comorbidities, selective eosinophilic tissue infiltration, remarkable response to oral and intranasal corticosteroids, and progression in a type 2 CRSwNP.
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Avdeeva KS, Fokkens WJ, Segboer CL, Reitsma S. The prevalence of non-allergic rhinitis phenotypes in the general population: A cross-sectional study. Allergy 2022; 77:2163-2174. [PMID: 35038765 PMCID: PMC9306544 DOI: 10.1111/all.15223] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 12/01/2021] [Accepted: 12/21/2021] [Indexed: 12/24/2022]
Abstract
Background Non‐allergic rhinitis (NAR) can be subdivided into several phenotypes: rhinorrhea of the elderly, rhinitis medicamentosa, smokers', occupational, hormonal, drug‐induced, gustatory, and idiopathic rhinitis. There are two pathophysiological endotypes of NAR: inflammatory and neurogenic. Phenotypes may serve as an indicator of an underlying endotype and, therefore, help to guide the treatment. The prevalence of each phenotype in the general population is currently unknown. Methodology/Principal Cross‐sectional questionnaire‐based study in the general population of the Netherlands. Results The prevalence of chronic rhinitis in the general population was 40% (N = 558, of those, 65% had NAR and 28% AR, in 7% allergy status is unknown). Individuals with NAR (N = 363) had significantly more complaints in October–February. Those with AR (N = 159) had significantly more complaints in April–August. The most common NAR phenotypes were idiopathic (39%) and rhinitis medicamentosa (14%), followed by occupational (8%), smokers' (6%), hormonal (4%), gustatory (4%), and rhinorrhea of the elderly (4%). The least prevalent phenotype was drug induced (1%). Nineteen percent of the NAR group could not be classified into any of the phenotypes. Conclusions This is the first study to describe the prevalences of NAR phenotypes in the general population. AR and NAR have a distinct seasonality pattern with NAR being more prevalent in autumn/winter and AR in spring/summer. Our data on the prevalence of phenotypes may help clinicians to anticipate the type of patients at their clinic and help guide a tailored treatment approach. The high prevalence of rhinitis medicamentosa is alarming, since this is a potentially preventable phenotype.
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Affiliation(s)
- Klementina S. Avdeeva
- Department of Otorhinolaryngology Amsterdam UMC Location Academic Medical Centre Amsterdam The Netherlands
| | - Wytske J. Fokkens
- Department of Otorhinolaryngology Amsterdam UMC Location Academic Medical Centre Amsterdam The Netherlands
| | | | - Sietze Reitsma
- Department of Otorhinolaryngology Amsterdam UMC Location Academic Medical Centre Amsterdam The Netherlands
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Ito K, Tagami K. Distinct differences in analytical performance of two commercially available assays for specific IgE to egg white and house dust mite allergens. Clin Mol Allergy 2021; 19:13. [PMID: 34340696 PMCID: PMC8330041 DOI: 10.1186/s12948-021-00151-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 07/15/2021] [Indexed: 11/17/2022] Open
Abstract
Background Measurements of allergen-specific IgE antibodies with different manufacturers’ assays show modest or poor agreement. This study compares analytical performance of specific IgE tests for whole allergen extracts and individual allergen components of two assay systems, IMMULITE and ImmunoCAP, using human sera as well as monoclonal antibodies. Methods Comparisons were performed for specific IgE to house dust mite (HDM, n = 44), egg white (EW, n = 36) and the allergen components rDer p 1, rDer p 2, nGal d 1, nGal d 2 and nGal d 4 in human sera and with monoclonal mouse/human chimeric IgE antibodies specific for the same allergen components. Competitive interference with IgE measurement was investigated using allergen-specific monoclonal IgG and IgG4 antibodies. Results Measurements of IgE to HDM and EW in serial dilutions of human sera revealed weaker dilution linearity with IMMULITE than with ImmunoCAP. Analysis of five different monoclonal IgE antibodies with total and specific IgE assays, expected to return similar levels, gave an average specific/total IgE ratio of 0.96 (range 0.71–1.14) with ImmunoCAP and 1.89 (range 0.76–2.85) with IMMULITE, indicating overestimation of specific IgE by IMMULITE. With the EW IgE tests of both assay systems, measurements of a chimeric anti-Gal d 2 IgE antibody were unaffected by a competing mouse IgG antibody. While the same was true for measurement of a chimeric anti-Der p 1 IgE antibody using the HDM test in ImmunoCAP, a suppression of measured concentrations by up to 42% was observed in IMMULITE. Similarly, measurement of HDM-specific IgE in human sera by ImmunoCAP was unaffected by a competing monoclonal anti-Der p 2 IgG4 antibody while IMMULITE displayed a reduction of HDM-specific IgE values by up to 30%. Conclusions In this evaluation of analytical performance of two widely used assay systems, ImmunoCAP showed higher accuracy in quantitation of specific IgE and greater resistance against competing allergen-specific non-IgE antibodies which may arise through natural or dietary exposure, or as a result of allergen immunotherapy treatment.
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Affiliation(s)
- Komei Ito
- Allergy and Immunology Center, Aichi Children's Health and Medical Center, Obu, Aichi, Japan.
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Rhinitis Phenotypes. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2021; 8:1492-1503. [PMID: 32389274 DOI: 10.1016/j.jaip.2020.02.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 02/11/2020] [Accepted: 02/11/2020] [Indexed: 02/08/2023]
Abstract
Rhinitis is an umbrella term of a group of upper airway diseases with nasal symptoms and signs with different etiologies and various clinical features or traits. It can be classified into different "phenotypes," based on these observable traits. A proper differential diagnosis is necessary to adequately manage the disease. The objective of this review is to clarify the concept of rhinitis phenotypes while analyzing the clinical features and/or traits of each in order to determine a proper differential diagnosis and appropriate treatment.
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Meng Y, Wang C, Zhang L. Diagnosis and treatment of non-allergic rhinitis: focus on immunologic mechanisms. Expert Rev Clin Immunol 2020; 17:51-62. [PMID: 33259234 DOI: 10.1080/1744666x.2020.1858804] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Non-allergic rhinitis (NAR) is a heterogeneous nasal disease with high global prevalence. NAR can be subclassified as nonallergic rhinitis with eosinophilia syndrome (NARES), vasomotor rhinitis (VMR), and local allergic rhinitis (LAR). Although the precise factors involved in the etiology of NAR are not clear, there is evidence that immunological factors play an important role in the pathogenesis of NAR. This review provides a comprehensive overview of the immunological and neurogenic mechanisms involved in the diagnosis and treatment of NAR. AREAS COVERED This review provides a comprehensive overview of the immunological basis of diagnostic and treatment strategies for NARES, VMR, and LAR. In particular, recently documented molecular and immunological mechanisms of NAR are discussed, which may help to better understand the mechanisms underlying the pathologies of the different endotypes of NAR. EXPERT OPINION An increasing number of studies investigating the pathogenesis of NAR suggest that the immunological mechanisms underlying the different subtypes of NAR vary greatly, and are still not fully understood to accurately diagnose these subtypes. Thus, further studies should focus on making diagnosis and treatment of NAR more precise, safe, and effective. A better understanding of the immunological mechanisms involved in NAR should help in the discovery of new diagnostic and treatment strategies.
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Affiliation(s)
- Yifan Meng
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing China.,Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences
| | - Chengshuo Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing China.,Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing China.,Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences.,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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Li L, Liu Y, Wang Q, Wang Z, Cui L, Xu Y, Guan K. Levels of nasal exhaled hydrogen sulfide in the general population and allergic rhinitis patients. J Clin Lab Anal 2020; 35:e23678. [PMID: 33615571 PMCID: PMC7957977 DOI: 10.1002/jcla.23678] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 09/08/2020] [Accepted: 11/22/2020] [Indexed: 12/11/2022] Open
Abstract
Background Objective measures used for the differential diagnosis and severity assessment of allergic rhinitis (AR) are still lacking. The involvement of hydrogen sulfide (H2S) in the development of AR indicates that nasal exhaled H2S (NeH2S) has potential as a biomarker to be used in AR patients. This study aimed to evaluate the application value of NeH2S measurement in the diagnosis and assessment of AR. Methods This study was a multi‐center cross‐sectional survey conducted in Northwestern China. Demographic information collection and rhinitis assessment were completed through questionnaires. The level of NeH2S and serum immunoglobulin E were measured. Results The level of NeH2S in general population ranged from 0 to 35 ppb, with a median value of 2 ppb. The NeH2S levels in seasonal allergic rhinitis (SAR) patients were significantly lower than those in general population (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .023), and the NeH2S value of the SAR group tended to be lower than that of the non‐allergic rhinitis (NAR) group (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .094). The subgroup of AR patients with symptoms lasting longer than 2 weeks per month had a lower NeH2S level compared with the subgroup of patients with symptoms lasting less than 2 weeks per month (2 [1, 2] vs. 2 [2, 3] ppb; p = .015). Conclusion This study described the distribution range of NeH2S levels in the general population. Further study with larger sample size was needed to clarify the relationship between NeH2S level and AR.
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Affiliation(s)
- Lisha Li
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Yonglin Liu
- Department of Pediatrics, Shenmu Hospital, Shenmu, China
| | - Qiang Wang
- Department of Orthopedics, Shenmu Hospital, Shenmu, China
| | - Zixi Wang
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Le Cui
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Yingyang Xu
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Kai Guan
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
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Eckrich J, Hinkel J, Fischl A, Herrmann E, Holtappels G, Bachert C, Zielen S. Nasal IgE in subjects with allergic and non-allergic rhinitis. World Allergy Organ J 2020; 13:100129. [PMID: 32612737 PMCID: PMC7322186 DOI: 10.1016/j.waojou.2020.100129] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 05/09/2020] [Accepted: 05/12/2020] [Indexed: 01/15/2023] Open
Abstract
Purpose The prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students. Methods 131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM). Results In serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy. Conclusions Nasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.Study identifier at ClinicalTrials.gov: NCT02810535.
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Key Words
- AR, allergic rhinitis
- AR + HDM, allergic rhinitis with house dust mite allergy
- Allergic rhinitis
- D1, Dermatophagoides pteronyssinus
- D2, Dermatophagoides farinae
- FEV1, forced expiratory volume in one second
- FVC, forced vital capacity
- GCP, Good Clinical Practice
- HDM, house dust mite
- House dust mite allergy
- ISAAC, International Study of Asthma and Allergies in Childhood questionnaire
- LAR, local allergic rhinitis
- Local IgE
- Local allergic rhinitis
- NARES, non-allergic rhinitis with eosinophilia-syndrome
- NPT, nasal provocation tests
- Non-allergic-rhinitis
- PNIF, peak nasal inspiratory flow
- RAST, Radioallergosorbent Test
- SD, standard deviation
- SPT, skin prick test
- sIgE, allergen-specific IgE
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Affiliation(s)
- Jonas Eckrich
- Department of Otolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Julia Hinkel
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic Fibrosis, Goethe University, Frankfurt, Germany
| | - Anna Fischl
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic Fibrosis, Goethe University, Frankfurt, Germany
| | - Eva Herrmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt, Germany
| | | | - Claus Bachert
- Upper Airways Research Laboratory, Ghent University, B-9000 Ghent, Belgium
| | - Stefan Zielen
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic Fibrosis, Goethe University, Frankfurt, Germany
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Castelli S, Arasi S, Tripodi S, Villalta D, Martelli P, Conte M, Panetta V, Simonelli I, Rohrbach A, Di Fraia M, Sfika I, Villella V, Di Rienzo Businco A, Perna S, Dramburg S, Potapova E, Matricardi PM. IgE antibody repertoire in nasal secretions of children and adults with seasonal allergic rhinitis: A molecular analysis. Pediatr Allergy Immunol 2020; 31:273-280. [PMID: 31677297 DOI: 10.1111/pai.13148] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 10/24/2019] [Accepted: 10/25/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. OBJECTIVE To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. METHODS Nasal secretions were collected with an absorbent device (Merocel 2000® , Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC-112, TFS) were measured in NS and serum. RESULTS Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. CONCLUSIONS The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire.
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Affiliation(s)
- Sveva Castelli
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Stefania Arasi
- Division of Allergy, University Department of Pediatrics, Pediatric Hospital Bambino Gesù (IRCCS), Rome, Italy
| | - Salvatore Tripodi
- Department of Pediatrics and Pediatric Allergy Unit, Sandro Pertini Hospital, Rome, Italy
| | - Danilo Villalta
- Immunology and Allergy Unit, "S.Maria degli Angeli" Hospital, Pordenone, Italy
| | - Paola Martelli
- Immunology and Allergy Unit, "S.Maria degli Angeli" Hospital, Pordenone, Italy
| | | | - Valentina Panetta
- L'altrastatistica srl, Consultancy & Training, Biostatistics Office, Rome, Italy
| | - Ilaria Simonelli
- L'altrastatistica srl, Consultancy & Training, Biostatistics Office, Rome, Italy
| | - Alexander Rohrbach
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Marco Di Fraia
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ifigenia Sfika
- Department of Pediatrics and Pediatric Allergy Unit, Sandro Pertini Hospital, Rome, Italy
| | - Valeria Villella
- Department of Pediatrics and Pediatric Allergy Unit, Sandro Pertini Hospital, Rome, Italy
| | | | - Serena Perna
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Stephanie Dramburg
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ekaterina Potapova
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Paolo Maria Matricardi
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
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12
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Crisci CD, Ardusso LRF. A Precision Medicine Approach to Rhinitis Evaluation and Management. CURRENT TREATMENT OPTIONS IN ALLERGY 2020; 7:93-109. [PMID: 32226715 PMCID: PMC7099688 DOI: 10.1007/s40521-020-00243-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Precision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. The PM approach focuses on the characterization of different phenotypes and pathogenic pathways in order to allow the selection of specific biomarkers that will be useful in disease management. Rhinitis is a highly prevalent and heterogeneous disease, both in terms of underlying endotypes and clinical presentations. Therefore, to apply the PM principles to the various rhinitis subtypes rise as a meaningful strategy to improve evaluation and treatment. RECENT FINDINGS The technology of recombinant allergens has allowed molecular characterization of IgE reactivity of specific individual components of allergenic extracts. Recently published and ongoing clinical trials based on component resolved diagnosis (CRD) bring more precision to allergen immunotherapy for allergic rhinitis. Monoclonal antibodies against various cytokines involved in inflammatory allergic and nonallergic rhinitis endotypes show promissory results. SUMMARY Better understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with rhinitis symptoms contributes to point out clinical usefulness of biomarkers and other diagnostic tools, which leads to more accurate environmental control measures, personalized pharmacologic options, and new biological therapy developments.
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Affiliation(s)
- Carlos D. Crisci
- Department of Pulmonology Allergy and Immunology, School of Medicine, National University of Rosario, 2000 Rosario, Santa Fe Argentina
| | - Ledit R. F. Ardusso
- Department of Pulmonology Allergy and Immunology, School of Medicine, National University of Rosario, 2000 Rosario, Santa Fe Argentina
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13
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Santus P, Saad M, Damiani G, Patella V, Radovanovic D. Current and future targeted therapies for severe asthma: Managing treatment with biologics based on phenotypes and biomarkers. Pharmacol Res 2019; 146:104296. [PMID: 31173886 DOI: 10.1016/j.phrs.2019.104296] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 06/02/2019] [Accepted: 06/03/2019] [Indexed: 12/14/2022]
Abstract
Asthma is a respiratory disorder with considerable heterogeneity in aetiology, triggers, clinical characteristics and response to therapy. This diversity reflects different inflammatory pathways that can be subdivided into clinically similar categories called phenotypes, or pathogenically comparable groups called endotypes. In recent years, a great amount of research has been dedicated to the investigation and understanding of the heterogeneity of asthma pathophysiology and to the identification of treatable traits, biomarkers, mediators and therapeutic targets. Severe asthma is defined as an uncontrolled disease despite a maximal conventional therapeutic approach. While, to date, some target therapies showing improvements in lung function, asthma symptoms and a reduction of the annual rate of exacerbations in patients with severe asthma have been already approved, other treatments are currently being studied, specifically targeting Type 2 asthma. Further progress however, is still needed to tackle the molecular pathways for non-Type 2 asthma. The aim of the present narrative review is to discuss and examine the indication, mechanisms of action and therapeutic effects of currently available and emerging biologic agents for the treatment of severe asthma.
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Affiliation(s)
- Pierachille Santus
- Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Division of Pulmonary Diseases, Ospedale L. Sacco, ASST Fatebenfratelli-Sacco, Via G.B. Grassi, 74, 20157, Milan, Italy.
| | - Marina Saad
- Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Division of Pulmonary Diseases, Ospedale L. Sacco, ASST Fatebenfratelli-Sacco, Via G.B. Grassi, 74, 20157, Milan, Italy.
| | - Giovanni Damiani
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi, 4, 20161, Milan, Italy.
| | - Vincenzo Patella
- Allergology and Clinical Immunology Unit, Department of Medical Sciences, Battipaglia Hospital, Via Fiorignano, 1, 84091, Battipaglia, Salerno, Italy.
| | - Dejan Radovanovic
- Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Division of Pulmonary Diseases, Ospedale L. Sacco, ASST Fatebenfratelli-Sacco, Via G.B. Grassi, 74, 20157, Milan, Italy.
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14
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Hamizan AW, Azer M, Alvarado R, Earls P, Barham HP, Tattersall J, Rimmer J, Kalish L, Sewell WA, Harvey R. The Distinguishing Clinical Features of Nonallergic Rhinitis Patients. Am J Rhinol Allergy 2019; 33:524-530. [PMID: 31106562 DOI: 10.1177/1945892419850750] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Background Not all rhinitis patients are affected by an immunoglobulin E (IgE)-mediated inflammatory process. Skin and serum allergy assessments are limited in their ability to define local allergic rhinitis (LAR). Thus, patients with negative systemic allergy assessments comprise a mix of those who truly have nonallergic rhinitis (NAR) and patients with LAR. Objective To determine the clinical characteristics of patients with NAR. Methods A cross-sectional study was performed on consecutive adults with rhinitis symptoms who underwent turbinate surgery. NAR patients were defined by excluding allergy using both systemic (serum-specific IgE and/or skin prick test) and local (inferior turbinate tissue-specific IgE) tests. Allergic rhinitis (AR) patients were defined by any positive systemic or local test toward aeroallergens. The clinical characteristics studied included allergic comorbidities (asthma, eczema, allergic conjunctivitis), inhalant allergen triggers (dust, pollen, animal dander), and environmental triggers (Cincinnati Irritant Index [CII]). Results There were 154 participants (41.79 ± 14.78 years, 37.7% female). NAR patients (11.7%) were older (49.33 ± 15.99 vs 40.78 ± 14.38 years, P = .02), had less self-reported asthma (5.6% vs 36.3%, P < .01) and house dust inhalant trigger (38.9 vs 65.2%, P = .03) compared to AR patients. The CII score was similar for NAR and AR (31.06 ± 28.88 vs 35.49 ± 24.70, P = .61). Conclusion Patients who were older, without asthma, and lacked an inhalant allergy trigger were more likely to have true NAR. Environmental triggers are not distinguishing features of NAR. This may be used as a guide to identify rhinitis patients whose symptoms are truly nonallergic etiology compared to those with falsely negative systemic allergy assessment but may still need management for LAR.
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Affiliation(s)
- Aneeza W Hamizan
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,2 Department of Otorhinolaryngology, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Mark Azer
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Raquel Alvarado
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Peter Earls
- 3 Department of Anatomical Pathology, St Vincent's Hospital, Sydney, Australia
| | - Henry P Barham
- 4 Sinus and Nasal Specialists of Louisiana, Baton Rouge, Louisiana
| | - Jessica Tattersall
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Janet Rimmer
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,5 Upper Airway Research Group, Woolcock Institute, University of Sydney, Sydney, Australia.,6 Faculty of Medicine, Notre Dame University, Sydney, Australia.,7 Sydney Medical School, University of Sydney, Sydney, Australia
| | - Larry Kalish
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,7 Sydney Medical School, University of Sydney, Sydney, Australia.,8 Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, Australia
| | - William A Sewell
- 9 St Vincent's Clinical School, University of New South Wales Sydney, Sydney, Australia.,10 Immunology Division, Garvan Institute, Sydney, Australia
| | - Richard Harvey
- 1 Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,11 Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
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15
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Rondón C, Eguiluz-Gracia I, Campo P. Is the evidence of local allergic rhinitis growing? Curr Opin Allergy Clin Immunol 2019; 18:342-349. [PMID: 29847361 DOI: 10.1097/aci.0000000000000456] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
PURPOSE OF REVIEW To examine the recent advances on epidemiological studies, diagnostic approach and clinical management of local allergic rhinitis (LAR) in adults and children. RECENT FINDINGS Evidence about LAR is growing especially in pediatric and Asian populations. The prevalence of LAR is lower in Asian countries compared with western countries in both children and adults. LAR is considered a chronic condition and an independent rhinitis phenotype that affects up to 26.5% of nonatopic rhinitis patients. The disease rapidly progress toward the clinical worsening with associated onset of asthma and conjunctivitis, which further impairs patient's quality of life. Nasal Allergen Provocation Test is the diagnostic gold standard that can be complemented by basophil activation test and the detection of specific IgE in nasal secretions. Allergen immunotherapy induces a significant and early improvement in both clinical symptoms and quality of life in LAR patients. SUMMARY LAR is a common entity, with different prevalence depending on geographical locations. LAR has to be considered in the process of differential diagnosis in children and adults with rhinitis. Diagnosis of LAR is crucial in order to start an etiologic treatment such as allergen immunotherapy, which has proven to be very effective in these patients.
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Affiliation(s)
- Carmen Rondón
- Allergy Unit, Hospital Regional Universitario de Malaga-IBIMA, ARADyAL, Malaga, Spain
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16
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Rondón C, Eguíluz-Gracia I, Shamji MH, Layhadi JA, Salas M, Torres MJ, Campo P. IgE Test in Secretions of Patients with Respiratory Allergy. Curr Allergy Asthma Rep 2018; 18:67. [PMID: 30317418 DOI: 10.1007/s11882-018-0821-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW IgE is a key player in multiple inflammatory airway diseases. Ample literature demonstrates its presence in mucosa of patients with allergic rhinitis (AR), local allergic rhinitis (LAR), asthma, or chronic rhinosinusitis with nasal polyposis (CRSwNP). RECENT FINDINGS Current evidence shows that high-affinity IgE in blood stream of allergic individuals derives mainly from the mucosae. Also, mucosal synthesis of IgE can occur in the absence of systemic atopy, and may be relevant in atopic and non-atopic phenotypes of rhinitis as demonstrated in LAR. Specific IgE (sIgE) detection varies depending on technique used for sample collection and its measurement. sIgE detection is highly specific for diagnosis of LAR. Moreover, measurement of sIgE in secretions could be useful in monitoring response to allergen-specific immunotherapy in both AR and LAR phenotypes. This review will focus on recent developments in the role of IgE in respiratory diseases, and the clinical implications of its measurement in secretions.
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Affiliation(s)
- Carmen Rondón
- Allergy Unit, IBIMA-Regional University Hospital of Málaga, Málaga, Spain
| | | | - Mohamed H Shamji
- Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, MRC Asthma UK Centre Imperial College London, London, UK
| | - Janice A Layhadi
- Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, MRC Asthma UK Centre Imperial College London, London, UK
| | - María Salas
- Allergy Unit, IBIMA-Regional University Hospital of Málaga, Málaga, Spain
| | - María José Torres
- Allergy Unit, IBIMA-Regional University Hospital of Málaga, Málaga, Spain
| | - Paloma Campo
- Allergy Unit, IBIMA-Regional University Hospital of Málaga, Málaga, Spain.
- Plaza Hospital Civil, 29009, Málaga, Spain.
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17
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Yii ACA, Tay T, Choo XN, Koh MSY, Tee AKH, Wang D. Precision medicine in united airways disease: A "treatable traits" approach. Allergy 2018; 73:1964-1978. [PMID: 29869791 DOI: 10.1111/all.13496] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2018] [Indexed: 12/21/2022]
Abstract
United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms). The UAD paradigm also extends to myriad sinonasal diseases (eg, chronic rhinosinusitis with or without nasal polyps) and lower airway diseases (eg, bronchiectasis, chronic obstructive pulmonary disease). Here, we review currently known phenoendotypes of UAD and propose a "treatable traits" approach for the classification and management of UAD, wherein pathophysiological mechanisms and factors contributing to disease are identified and targeted for treatment. Treatable traits in UAD can be analyzed according to a framework comprising airway inflammation (eosinophilic, neutrophilic), impaired airway mucosal defense (impaired mucociliary clearance, antibody deficiency), and exogenous cofactors (allergic sensitizers, tobacco smoke, microbes). Appreciation of treatable traits is necessary in advancing the effort to deliver precise treatments and achieve better outcomes in patients with UAD.
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Affiliation(s)
- A. C. A. Yii
- Department of Respiratory and Critical Care Medicine Changi General Hospital Singapore
- Duke‐National University of Singapore Medical School Singapore
| | - T.‐R. Tay
- Department of Respiratory and Critical Care Medicine Changi General Hospital Singapore
| | - X. N. Choo
- Department of Respiratory and Critical Care Medicine Changi General Hospital Singapore
| | - M. S. Y. Koh
- Department of Respiratory and Critical Care Medicine Singapore General Hospital Singapore
- Duke‐National University of Singapore Medical School Singapore
| | - A. K. H. Tee
- Department of Respiratory and Critical Care Medicine Changi General Hospital Singapore
| | - D.‐Y. Wang
- Department of Otolaryngology National University of Singapore Singapore
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18
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Yu H, Ju J, Liu J, Li D. Aberrant expression of miR-663 and transforming growth factor-β1 in nasal polyposis in children. Exp Ther Med 2018; 15:4550-4556. [PMID: 29849780 DOI: 10.3892/etm.2018.5927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 04/11/2017] [Indexed: 12/22/2022] Open
Abstract
The aim of the present study was to investigate the expression of microRNA (miR)-663 and its regulatory effects on the pathogenesis of nasal polyposis in children. Nasal polyp tissue, as well as serum and peripheral blood eosinophils were collected from 35 children diagnosed with nasal polypectomy between August 2013 and August 2015. As a control, the inferior nasal concha, serum and peripheral blood eosinophils were collected from 46 patients with nasal septal deviation complicated by inferior turbinate hypertrophy or patients with simple inferior turbinate hypertrophy who had undergone surgical removal of the inferior nasal concha. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of miR-663 and transforming growth factor-β1 (TGF-β1) in the nasal polyp tissue, serum and peripheral blood eosinophils of patients with nasal polyposis and controls. Western blotting was used to measure the expression of TGF-β1 protein in nasal tissue and eosinophils and an enzyme-linked immunosorbent assay was used to measure serum level of TGF-β1 protein. A dual luciferase reporter assay was used to determine whether TGF-β1 was a target gene of miR-663. Compared with the control group, levels of TGF-β1 mRNA and protein were significantly increased in all three types of specimens from pediatric patients with nasal polyposis (P<0.05). miR-663 expression was significantly decreased in nasal polyp tissue and peripheral blood eosinophils (P<0.05). The dual luciferase reporter assay confirmed that TGF-β1 was a target gene of miR-663. The current study suggests that the upregulation of TGF-β1 may be associated with the downregulation of miR-663 in nasal polyposis in children. miR-663 may have regulatory effects on the pathogenesis of nasal polyposis by regulating TGF-β1 and may be developed as a genetic marker of nasal polyposis in children.
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Affiliation(s)
- Hailing Yu
- Department of Otolaryngology, The Women and Children's Hospital of Qingdao, Qingdao, Shandong 266033, P.R. China
| | - Jianbao Ju
- Department of Otolaryngology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266033, P.R. China
| | - Jingdong Liu
- Department of Medicine, The Women and Children's Hospital of Qingdao, Qingdao, Shandong 266033, P.R. China
| | - Da Li
- Department of Otolaryngology, The Women and Children's Hospital of Qingdao, Qingdao, Shandong 266033, P.R. China
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Chaker AM. [Biologics in Rhinology - Forthcoming Personalized Concepts: the Future Starts Today]. Laryngorhinootologie 2018; 97:S142-S184. [PMID: 29905356 PMCID: PMC6541111 DOI: 10.1055/s-0043-123484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Sinunasale Erkrankungen zählen mit zu den häufigsten chronischen Erkrankungen und führen zu einer erheblichen Störung der Lebensqualität, ein komorbides Asthma ist häufig. Trotz leitliniengerechter Therapie ist anzunehmen, dass mind. 20% der Patienten ihre Erkrankungssymptome nicht adäquat kontrollieren können. Neben den etablierten chirurgischen und konservativen Therapieoptionen finden sich nun vielversprechende Therapieansätze, die bspw. mittels therapeutischer Antikörper mechanistisch gezielt in die Pathophysiologie der Erkrankungen eingreifen können. Die Auswahl der geeigneten Patienten durch geeignete Biomarker und die richtige Therapie zum richtigen Stadium der Erkrankung anbieten zu können, ist das Ziel stratifizierter Medizin und eine wichtige Perspektive für die HNO.Chronic diseases of the nose and the paranasal sinuses are most common, frequently associated with bronchial asthma, and result in substantial reduction of quality of life. Despite optimal treatment according to guidelines, approx. 20 % of the patients will report inadequate control of symptoms. Apart from well established surgical and conservative approaches in therapy new therapeutic antibodies are available that aim specifically pathophysiological targets. The optimal allocation of effective therapy for patients using appropriate biomarkers at the most suitable timepoint is the hallmark of stratified medicine and an important perspective in ENT.
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Affiliation(s)
- Adam M. Chaker
- Klinik für Hals-Nasen-Ohrenheilkunde und Zentrum für Allergie und Umwelt, Klinikum rechts der Isar, Technische Universität München
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20
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Wise SK, Lin SY, Toskala E, Orlandi RR, Akdis CA, Alt JA, Azar A, Baroody FM, Bachert C, Canonica GW, Chacko T, Cingi C, Ciprandi G, Corey J, Cox LS, Creticos PS, Custovic A, Damask C, DeConde A, DelGaudio JM, Ebert CS, Eloy JA, Flanagan CE, Fokkens WJ, Franzese C, Gosepath J, Halderman A, Hamilton RG, Hoffman HJ, Hohlfeld JM, Houser SM, Hwang PH, Incorvaia C, Jarvis D, Khalid AN, Kilpeläinen M, Kingdom TT, Krouse H, Larenas-Linnemann D, Laury AM, Lee SE, Levy JM, Luong AU, Marple BF, McCoul ED, McMains KC, Melén E, Mims JW, Moscato G, Mullol J, Nelson HS, Patadia M, Pawankar R, Pfaar O, Platt MP, Reisacher W, Rondón C, Rudmik L, Ryan M, Sastre J, Schlosser RJ, Settipane RA, Sharma HP, Sheikh A, Smith TL, Tantilipikorn P, Tversky JR, Veling MC, Wang DY, Westman M, Wickman M, Zacharek M. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol 2018; 8:108-352. [PMID: 29438602 PMCID: PMC7286723 DOI: 10.1002/alr.22073] [Citation(s) in RCA: 234] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 12/01/2017] [Accepted: 12/01/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.
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Affiliation(s)
| | | | | | | | - Cezmi A. Akdis
- Allergy/Asthma, Swiss Institute of Allergy and Asthma Research, Switzerland
| | | | - Antoine Azar
- Allergy/Immunology, Johns Hopkins University, USA
| | | | | | | | | | - Cemal Cingi
- Otolaryngology, Eskisehir Osmangazi University, Turkey
| | | | | | | | | | | | | | - Adam DeConde
- Otolaryngology, University of California San Diego, USA
| | | | | | | | | | | | | | - Jan Gosepath
- Otorhinolaryngology, Helios Kliniken Wiesbaden, Germany
| | | | | | | | - Jens M. Hohlfeld
- Respiratory Medicine, Hannover Medical School, Airway Research Fraunhofer Institute for Toxicology and Experimental Medicine, German Center for Lung Research, Germany
| | | | | | | | | | | | | | | | | | | | | | | | | | - Amber U. Luong
- Otolaryngology, McGovern Medical School at the University of Texas Health Science Center Houston, USA
| | | | | | | | - Erik Melén
- Pediatric Allergy, Karolinska Institutet, Sweden
| | | | | | - Joaquim Mullol
- Otolaryngology, Universitat de Barcelona, Hospital Clinic, IDIBAPS, Spain
| | | | | | | | - Oliver Pfaar
- Rhinology/Allergy, Medical Faculty Mannheim, Heidelberg University, Center for Rhinology and Allergology, Wiesbaden, Germany
| | | | | | - Carmen Rondón
- Allergy, Regional University Hospital of Málaga, Spain
| | - Luke Rudmik
- Otolaryngology, University of Calgary, Canada
| | - Matthew Ryan
- Otolaryngology, University of Texas Southwestern, USA
| | - Joaquin Sastre
- Allergology, Hospital Universitario Fundacion Jiminez Diaz, Spain
| | | | | | - Hemant P. Sharma
- Allergy/Immunology, Children's National Health System, George Washington University School of Medicine, USA
| | | | | | | | | | | | - De Yun Wang
- Otolaryngology, National University of Singapore, Singapore
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Incorvaia C, Fuiano N, Martignago I, Gritti BL, Ridolo E. Local allergic rhinitis: evolution of concepts. Clin Transl Allergy 2017; 7:38. [PMID: 29118971 PMCID: PMC5669011 DOI: 10.1186/s13601-017-0174-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 10/21/2017] [Indexed: 01/12/2023] Open
Abstract
The discovery of an exclusive local production of IgE antibodies dates back to the 1970s, but only recently the pathophysiology of such phenomenon was deeply investigated, leading to the concept of local allergic rhinitis (LAR). Currently, LAR is defined by the occurrence, in patients with symptoms clearly suggesting allergic rhinitis but with negative results to common allergy testing, of allergen specific IgE in the nasal mucosa. Most studies investigating LAR were based on the development of rhinitis symptoms following nasal provocation test (NPT) with the suspected allergens, but such test may be performed by a number of options, none of them being as yet acknowledged and recommended in consensus document. On the other hand, also the mere detection of IgE in the nasal mucosa indicates, as for IgE measurement in blood or other tissues, allergic sensitization but cannot give the certainty of clinical allergy. Therefore, the combination of IgE detection in nasal mucosa and a positive result of NPT should be used to diagnose LAR. Recent data on the use for in vitro testing of molecular allergy diagnostics in place of whole allergen extracts suggest that this method could improve the sensitivity and specificity of laboratory tests, and an appraisal of the basophil activation test as a third level technique, to be implemented when the results of local IgE testing and NPT are uncertain, is currently ongoing.
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Affiliation(s)
| | - Nicola Fuiano
- Pediatric Immunology and Allergy Service, San Severo, Italy
| | - Irene Martignago
- Medicine and Surgery Department, University of Parma, Via Gramsci 14, 43100 Parma, Italy
| | - Bruna L Gritti
- Cardiac/Pulmonary Rehabilitation, ASST Pini/CTO, Milan, Italy
| | - Erminia Ridolo
- Medicine and Surgery Department, University of Parma, Via Gramsci 14, 43100 Parma, Italy
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Ramanathan M, London NR, Tharakan A, Surya N, Sussan TE, Rao X, Lin SY, Toskala E, Rajagopalan S, Biswal S. Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice. Am J Respir Cell Mol Biol 2017; 57:59-65. [PMID: 28245149 PMCID: PMC5516278 DOI: 10.1165/rcmb.2016-0351oc] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 02/14/2017] [Indexed: 12/17/2022] Open
Abstract
Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 μm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 μm/m3, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.
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Affiliation(s)
- Murugappan Ramanathan
- Johns Hopkins Department of Otolaryngology–Head and Neck Surgery, Baltimore, Maryland
| | - Nyall R. London
- Johns Hopkins Department of Otolaryngology–Head and Neck Surgery, Baltimore, Maryland
| | - Anuj Tharakan
- Johns Hopkins Department of Otolaryngology–Head and Neck Surgery, Baltimore, Maryland
| | - Nitya Surya
- Johns Hopkins Department of Otolaryngology–Head and Neck Surgery, Baltimore, Maryland
| | - Thomas E. Sussan
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Xiaoquan Rao
- Cardiovascular Research Institute, Case Western Reserve School of Medicine, Cleveland, Ohio, and
| | - Sandra Y. Lin
- Johns Hopkins Department of Otolaryngology–Head and Neck Surgery, Baltimore, Maryland
| | - Elina Toskala
- Temple University Department of Otolaryngology–Head and Neck Surgery, Philadelphia, Pennsylvania
| | - Sanjay Rajagopalan
- Cardiovascular Research Institute, Case Western Reserve School of Medicine, Cleveland, Ohio, and
| | - Shyam Biswal
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
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Iwasaki N, Matsushita K, Fukuoka A, Nakahira M, Matsumoto M, Akasaki S, Yasuda K, Shimizu T, Yoshimoto T. Allergen endotoxins induce T-cell–dependent and non–IgE-mediated nasal hypersensitivity in mice. J Allergy Clin Immunol 2017; 139:258-268.e10. [DOI: 10.1016/j.jaci.2016.03.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 03/04/2016] [Accepted: 03/16/2016] [Indexed: 12/18/2022]
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Rondón C, Bogas G, Barrionuevo E, Blanca M, Torres MJ, Campo P. Nonallergic rhinitis and lower airway disease. Allergy 2017; 72:24-34. [PMID: 27439024 DOI: 10.1111/all.12988] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2016] [Indexed: 12/17/2022]
Abstract
In the past years, several investigators have demonstrated the existence of local nasal responses in some patients with typical allergic rhinitis symptoms but without atopy and have defined a new phenotype called local allergic rhinitis (LAR) or 'entopy'. In a percentage of LAR subjects, the upper airway disease is also associated with lower airway symptoms. After the description of this phenotype, the differential diagnosis between LAR and nonallergic rhinitis (NAR) has become a challenge for the clinician. To correctly identify LAR patients is of high importance for treatment and management of these patients, and for an appropriate inclusion of patients in clinical trials and genetics studies. The treatment of LAR patients, in contrast with NAR, is oriented to allergen avoidance and specific treatment. Allergen immunotherapy, the aetiological treatment for allergic respiratory diseases, has demonstrated to be an effective and safe treatment in LAR, increasing immunological tolerance, and reducing the clinical symptoms and the use of medication. In this article, the important and novel aspects of LAR in terms of mechanisms, diagnosis and treatment will be discussed. Also, the involvement of the lower airway and the potential role of IgE in the bronchial disease will be also reviewed.
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Affiliation(s)
- C. Rondón
- Allergy Unit; IBIMA-Regional University Hospital of Málaga; UMA; Malaga Spain
| | - G. Bogas
- Allergy Unit; IBIMA-Regional University Hospital of Málaga; UMA; Malaga Spain
| | - E. Barrionuevo
- Allergy Unit; IBIMA-Regional University Hospital of Málaga; UMA; Malaga Spain
| | - M. Blanca
- Allergy Unit; IBIMA-Regional University Hospital of Málaga; UMA; Malaga Spain
| | - M. J. Torres
- Allergy Unit; IBIMA-Regional University Hospital of Málaga; UMA; Malaga Spain
| | - P. Campo
- Allergy Unit; IBIMA-Regional University Hospital of Málaga; UMA; Malaga Spain
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Poddighe D, Gelardi M, Licari A, del Giudice MM, Marseglia GL. Non-allergic rhinitis in children: Epidemiological aspects, pathological features, diagnostic methodology and clinical management. World J Methodol 2016; 6:200-213. [PMID: 28074172 PMCID: PMC5183989 DOI: 10.5662/wjm.v6.i4.200] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 09/18/2016] [Accepted: 11/01/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic rhinitis is a very common disease, as the prevalence in the general population resulted to be 40%. Allergic rhinitis has been considered to be the most frequent form of chronic rhinitis, as non-allergic rhinitis has been estimated to account for 25%. However, several evidences suggested that non-allergic rhinitis have been underrated, especially in children. In pediatrics, the diagnostic definition of non-allergic rhinitis has been often limited to the exclusion of an allergic sensitization. Actually, local allergic rhinitis has been often misdiagnosed as well as mixed rhinitis has not been recognized in most cases. Nasal cytology is a diagnostic procedure being suitable for routine clinical practice with children and could be a very useful tool to characterize and diagnose non-allergic rhinitis, providing important clues for epidemiological analysis and clinical management.
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