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Agache I, Antolin‐Amerigo D, Blay F, Boccabella C, Caruso C, Chanez P, Couto M, Covar R, Doan S, Fauquert J, Gauvreau G, Gherasim A, Klimek L, Lemiere C, Nair P, Ojanguren I, Peden D, Perez‐de‐Llano L, Pfaar O, Rondon C, Rukhazde M, Sastre J, Schulze J, Silva D, Tarlo S, Toppila‐Salmi S, Walusiak‐Skorupa J, Zielen S, Eguiluz‐Gracia I. EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities. Allergy 2022; 77:1667-1684. [PMID: 34978085 DOI: 10.1111/all.15203] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 12/16/2021] [Accepted: 12/27/2021] [Indexed: 12/22/2022]
Abstract
Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways.
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Affiliation(s)
- Ioana Agache
- Faculty of Medicine Transylvania University Brasov Romania
| | - Dario Antolin‐Amerigo
- Servicio de Alergia Hospital Universitario Ramón y Cajal Instituto Ramón y Cajal de Investigación Sanitaria Madrid Spain
| | - Frederic Blay
- ALYATEC Environmental Exposure Chamber Chest Diseases Department Strasbourg University Hospital University of Strasbourg Strasbourg France
| | - Cristina Boccabella
- Department of Cardiovascular and Thoracic Sciences Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario A. Gemelli ‐ IRCCS Rome Italy
| | | | - Pascal Chanez
- Department of Respiratory CIC Nord INSERMINRAE C2VN Aix Marseille University Marseille France
| | - Mariana Couto
- Centro de Alergia Hospital CUF Descobertas Lisboa Portugal
| | - Ronina Covar
- Pediatrics National Jewish Health Denver Colorado USA
| | | | | | - Gail Gauvreau
- Division of Respirology Department of Medicine McMaster University Hamilton Ontario Canada
| | - Alina Gherasim
- ALYATEC Environmental Exposure Chamber Strasbourg France
| | - Ludger Klimek
- Center for Rhinology and Allergology Wiesbaden Germany
| | - Catherine Lemiere
- Research Centre Centre Intégré Universitaire de santé et de services sociaux du Nord‐de‐l'île‐de‐Montréal Montréal Quebec Canada
- Faculty of Medicine Université de Montreal Montreal Quebec Canada
| | - Parameswaran Nair
- Department of Medicine Firestone Institute of Respiratory Health at St. Joseph's Healthcare McMaster University Hamilton Ontario Canada
| | - Iñigo Ojanguren
- Departament de Medicina Servei de Pneumología Hospital Universitari Valld´Hebron Universitat Autònoma de Barcelona (UAB) Institut de Recerca (VHIR) CIBER de Enfermedades Respiratorias (CIBERES) Barcelona Spain
| | - David Peden
- Division of Pediatric Allergy and Immunology Center for Environmental Medicine, Asthma and Lung Biology The School of Medicine The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Luis Perez‐de‐Llano
- Department of Respiratory Medicine University Hospital Lucus Augusti Lugo Spain
| | - Oliver Pfaar
- Section of Rhinology and Allergy Department of Otorhinolaryngology, Head and Neck Surgery University Hospital Marburg Philipps‐Universität Marburg Marburg Germany
| | - Carmen Rondon
- Allergy Unit Hospital Regional Universitario de Malaga Instituto de Investigacion Biomedica de Malaga (IBIMA) Malaga Spain
| | - Maia Rukhazde
- Center of Allergy & Immunology Teaching University Geomedi LLC Tbilisi Georgia
| | - Joaquin Sastre
- Allergy Unit Hospital Universitario Fundación Jiménez Díaz Center for Biomedical Network of Respiratory Diseases (CIBERES) Instituto de Salud Carlos III (ISCIII) Madrid Spain
| | - Johannes Schulze
- Department for Children and Adolescents, Division of Allergology Pulmonology and Cystic Fibrosis Goethe‐University Hospital Frankfurt am Main Germany
| | - Diana Silva
- Basic and Clinical Immunology Unit Department of Pathology Faculty of Medicine University of Porto and Serviço de Imunoalergologia Centro Hospitalar São João, EPE Porto Portugal
| | - Susan Tarlo
- Respiratory Division Department of Medicine University Health Network, Toronto Western Hospital University of Toronto Department of Medicine, and Dalla Lana Department of Public Health Toronto Ontario Canada
| | - Sanna Toppila‐Salmi
- Haartman Institute, Medicum, Skin and Allergy Hospital Hospital District of Helsinki and Uusimaa Helsinki University Hospital and University of Helsinki Helsinki Finland
| | - Jolanta Walusiak‐Skorupa
- Department of Occupational Diseases and Environmental Health Nofer Institute of Occupational Medicine Łódź Poland
| | - Stefan Zielen
- Department for Children and Adolescents, Division of Allergology Pulmonology and Cystic Fibrosis Goethe‐University Hospital Frankfurt am Main Germany
| | - Ibon Eguiluz‐Gracia
- Allergy Unit Hospital Regional Universitario de Malaga Instituto de Investigacion Biomedica de Malaga (IBIMA) Malaga Spain
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Fischl A, Eckrich J, Passlack V, Klenke SK, Hartmann D, Herrmann E, Schulze J, Zielen S. Comparison of bronchial and nasal allergen provocation in children and adolescents with bronchial asthma and house dust mite sensitization. Pediatr Allergy Immunol 2020; 31:143-149. [PMID: 31660641 DOI: 10.1111/pai.13147] [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: 07/29/2019] [Revised: 10/09/2019] [Accepted: 10/10/2019] [Indexed: 01/10/2023]
Abstract
BACKGROUND Bronchial allergen provocation (BAP) is an established tool for the diagnosis of allergy in patients with asthma, but its use is limited by the potential risk of severe asthmatic reactions. Nasal provocation testing (NPT) may be an alternative safe method and does not require sophisticated equipment. OBJECTIVE The aim of this prospective study was to evaluate the concordance of both methods in patients with asthma and house dust mite (HDM) sensitization. METHODS A total of 112 patients with HDM sensitization underwent BAP and had the following parameters analysed: decrease in FEV1, exhaled NO, and total and specific IgE. Within 12 weeks, NPT with HDM was performed in 74 patients with a median age of 9 years (range, 5-16 years). The results were evaluated using the Lebel score which quantifies major symptoms like rhinorrhea, nasal obstruction, sneezes and minor symptoms, such as pruritus, conjunctivitis and pharyngitis. RESULTS Fifty-seven of 74 patients had an early asthmatic reaction, of which 41 were identified using the Lebel score. The Lebel score had a sensitivity of 71.9% and a positive predictive value (PPV) of 89.1%. In addition, an eNO ≥ 10 ppb (AUC 0.78), a specific IgE Dermatophagoïdes pteronyssinus ≥ 25.6 kU/L (AUC 0.76) and a specific IgE Dermatophagoïdes farinae ≥ 6.6 kU/L (AUC 0.78) were good predictors of an early asthmatic reaction. CONCLUSION A sequential use of NPT prior to BAP is justified to establish the relevance of HDM allergy. In patients with a negative NPT, BAP is still recommended to rule out a HDM-induced asthmatic reaction.
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Affiliation(s)
- Anna Fischl
- Department for Children and Adolescents, Division of Pediatric Allergy, Pulmonology, and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Jonas Eckrich
- Department of Otolaryngology, Head and Neck Surgery, School of Medicine, University of Mainz, Mainz, Germany
| | - Vanessa Passlack
- Department for Children and Adolescents, Division of Pediatric Allergy, Pulmonology, and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Sara-Kristin Klenke
- Department for Children and Adolescents, Division of Pediatric Allergy, Pulmonology, and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Desiree Hartmann
- Department for Children and Adolescents, Division of Pediatric Allergy, Pulmonology, and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Eva Herrmann
- Institute of Biostatistics and Mathematical Modelling, Goethe University, Frankfurt, Germany
| | - Johannes Schulze
- Department for Children and Adolescents, Division of Pediatric Allergy, Pulmonology, and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Stefan Zielen
- Department for Children and Adolescents, Division of Pediatric Allergy, Pulmonology, and Cystic fibrosis, Goethe University, Frankfurt, Germany
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Eickmeier O, Zissler UM, Wittschorek J, Unger F, Schmitt-Grohé S, Schubert R, Herrmann E, Zielen S. Clinical relevance of Aspergillus fumigatus sensitization in cystic fibrosis. Clin Exp Allergy 2020; 50:325-333. [PMID: 31886564 DOI: 10.1111/cea.13557] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 12/04/2019] [Accepted: 12/12/2019] [Indexed: 12/12/2022]
Abstract
RATIONALE The clinical relevance of sensitization to Aspergillus (A) fumigatus in cystic fibrosis (CF) is unclear. Some researchers propose that specific A fumigatus IgE is an innocent bystander, whereas others describe it as the major cause of TH-2-driven asthma-like disease. OBJECTIVES Lung function parameters in mild CF patients may be different in patients with and without A fumigatus sensitization. We aimed to ascertain whether allergen exposure to A fumigatus by bronchial allergen provocation (BAP) induces TH-2 inflammation comparable to an asthma-like disease. METHODS A total of 35 patients, aged 14.8 ± 8.5 years, and 20 healthy controls were investigated prospectively. The patients were divided into two groups: group 1 (n = 18): specific (s)IgE negative, and group 2 (n = 17): sIgE positive (≥0.7 KU/L) for A fumigatus. Lung function, exhaled NO, and induced sputum were analysed. All sensitized patients with an FEV1 > 75% (n = 13) underwent BAP with A fumigatus, and cell counts, and the expression of IL-5, IL-13, INF-γ, and IL-8 as well as transcription factors T-bet, GATA-3, and FoxP3, were measured. RESULTS Lung function parameters decreased significantly compared to controls, but not within the CF patient group. After BAP, 8 of 13 patients (61%) had a significant asthmatic response and increased eNO 24 hours later. In addition, marked TH-2-mediated inflammation involving eosinophils, IL-5, IL-13, and FoxP3 became apparent in induced sputum cells. CONCLUSION Our study demonstrated the clinical relevance of A fumigatus for the majority of sensitized CF patients. A distinct IgE/TH-2-dominated inflammation was found in induced sputum after A fumigatus exposure.
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Affiliation(s)
- Olaf Eickmeier
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Ulrich M Zissler
- Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center for Lung Research (DZL), CPC-M, Munich, Germany
| | - Julia Wittschorek
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Frederike Unger
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Sabina Schmitt-Grohé
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic fibrosis, Goethe University, Frankfurt, Germany
| | - Ralf Schubert
- 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
| | - Stefan Zielen
- Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic fibrosis, Goethe University, Frankfurt, Germany
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Hartmann D, Fischl A, Herrmann E, Schulze J, Schubert R, Zielen S. Prospective comparison of a nonmodified and a modified mite extract for immunotherapy in children and adolescents. Immunotherapy 2019; 11:1015-1029. [PMID: 31319714 DOI: 10.2217/imt-2019-0015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This prospective study compares nonmodified and modified house dust mite extracts for allergen immunotherapy (AIT) in pediatric patients with allergic asthma. Materials & methods: Total 95 patients underwent bronchial allergen provocation (BAP). AIT was recommended to 62 patients. Complete datasets of 54 subjects were obtained. Primary aim was the comparison of treatment success defined by BAP between two extracts after 1 year. Secondary parameters were laboratory parameters and clinical symptoms. Results: Significant improvement (p < 0.001) was measured by BAP in both treatment groups. No change was seen in the controls. Both extracts exerted comparable effects on all parameters. Conclusion: After 1 year of AIT, the extracts were equally efficient, with significant improvements in 70.0% (nonmodified) and 72.2% (modified) of patients.
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Affiliation(s)
- Desireé Hartmann
- Department for Children & Adolescents, Division of Allergology, Pulmonology & Cystic fibrosis, Goethe University, 60590 Frankfurt am Main, Germany
| | - Anna Fischl
- Department for Children & Adolescents, Division of Allergology, Pulmonology & Cystic fibrosis, Goethe University, 60590 Frankfurt am Main, Germany
| | - Eva Herrmann
- Department of Biostatistics, Goethe University, 60590 Frankfurt am Main, Germany
| | - Johannes Schulze
- Department for Children & Adolescents, Division of Allergology, Pulmonology & Cystic fibrosis, Goethe University, 60590 Frankfurt am Main, Germany
| | - Ralf Schubert
- Department for Children & Adolescents, Division of Allergology, Pulmonology & Cystic fibrosis, Goethe University, 60590 Frankfurt am Main, Germany
| | - Stefan Zielen
- Department for Children & Adolescents, Division of Allergology, Pulmonology & Cystic fibrosis, Goethe University, 60590 Frankfurt am Main, Germany
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Popescu FD, Vieru M. Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules. World J Methodol 2018; 8:17-36. [PMID: 30519536 PMCID: PMC6275558 DOI: 10.5662/wjm.v8.i3.17] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 08/17/2018] [Accepted: 10/09/2018] [Indexed: 02/06/2023] Open
Abstract
Molecular-based allergy diagnosis for the in vitro assessment of a patient immunoglobulin E (IgE) sensitization profile at the molecular level uses allergen molecules (also referred to as allergen components), which may be well-defined, highly purified, natural allergen components or recombinant allergens. Modern immunoassay methods used for the detection of specific IgE against aeroallergen components are either singleplex (such as the fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens, the enzyme-enhanced chemiluminescence immunoassay and the reversed enzyme allergosorbent test, with liquid-phase allergens), multiparameter (such as the line blot immunoassay for defined partial allergen diagnostics with allergen components coating membrane strips) or multiplex (such as the microarray-based immunoassay on immuno solid-phase allergen chip, and the two new multiplex nanotechnology-based immunoassays: the patient-friendly allergen nano-bead array, and the macroarray nanotechnology-based immunoassay used as a molecular allergy explorer). The precision medicine diagnostic work-up may be organized as an integrated “U-shape” approach, with a “top-down” approach (from symptoms to molecules) and a “bottom-up” approach (from molecules to clinical implications), as needed in selected patients. The comprehensive and accurate IgE sensitization molecular profiling, with identification of the relevant allergens, is indicated within the framework of a detailed patient’s clinical history to distinguish genuine IgE sensitization from sensitization due to cross-reactivity (especially in polysensitized patients), to assess unclear symptoms and unsatisfactory response to treatment, to reveal unexpected sensitizations, and to improve assessment of severity and risk aspects in some patients. Practical approaches, such as anamnesis molecular thinking, laboratory molecular thinking and postmolecular anamnesis, are sometimes applied. The component-resolved diagnosis of the specific IgE repertoire has a key impact on optimal decisions making for prophylactic and specific immunotherapeutic strategies tailored for the individual patient.
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Affiliation(s)
- Florin-Dan Popescu
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
| | - Mariana Vieru
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
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Mannan S. Allergen immunotherapy. Immunotherapy 2017; 9:1199-1200. [PMID: 29130796 DOI: 10.2217/imt-2017-0157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Sonia Mannan
- Future Science Group, Unitec House, 2 Albert Place, London, N3 1QB, UK
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