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The absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. (Clinical Physiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.ORCID iD: 0000-0001-5093-6980
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2018 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 6, p. 722-730Article in journal (Refereed) Published
Abstract [en]

Background:

Atopic asthma is associated with elevated type-2 biomarkers such as fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count. However, increased type 2 markers have also been reported in traditionally defined non-atopic asthma.

Objective:

To determine a clinically useful level of IgE sensitization for ruling out type 2 asthma. Methods: Asthmatics (N=408; age 10-35years) were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: 0.35kU(A)/L for at least one test (n=326) or <0.35kU(A)/L for both tests (n=82). he latter group was subsequently divided into 2 groups: IgE 0.10-0.34kU(A)/L (n=34) and IgE<0.10kU(A)/L (n=48). The relationships between type 2 biomarkers, and inadequate asthma control (ACT<20), reduced lung function (FEV1<80%), recent asthma attacks and airway hyperresponsiveness (AHR) to methacholine were determined.

Results:

In univariate analyses, at least one type 2 marker related to each asthma outcome in subjects with IgE 0.35kU(A)/L. In subjects with IgE 0.10-0.34kU(A)/L, elevated FeNO related to reduced lung function (P=.008) and B-Eos to AHR (P=.03). No associations were found in subjects with IgE<0.10kU(A)/L. In multivariate analysis, a relationship between FeNO and reduced lung function remained in subjects with IgE<0.35kU(A)/L (P=.03).

Conclusion and Clinical Relevance:

Clinically relevant elevation of type 2 biomarkers was seen in young asthmatics with IgE antibodies <0.35kU(A)/L, but not those with IgE<0.10kU(A)/L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018. Vol. 48, no 6, p. 722-730
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-343518DOI: 10.1111/cea.13103ISI: 000434080100012PubMedID: 29377450OAI: oai:DiVA.org:uu-343518DiVA, id: diva2:1186263
Funder
Swedish Foundation for Strategic Research Swedish Heart Lung FoundationSwedish Asthma and Allergy AssociationAvailable from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-11-26Bibliographically approved
In thesis
1. Study of biomarkers for improved diagnosis and therapy monitoring in young asthmatics
Open this publication in new window or tab >>Study of biomarkers for improved diagnosis and therapy monitoring in young asthmatics
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Type-2 asthma is often related to atopy and is characterized by elevated type-2 biomarkers. However, less is known about the pathophysiology of non-type 2 asthma, factors associated therewith, and the stability of different asthma phenotypes over time.

Aims: To identify an IgE antibody concentration and putative biomarkers that better separate non-type 2 from type-2 asthma. To study the association between longitudinal changes in inflammatory biomarkers and clinical outcomes. To investigate the pattern of IgE sensitization to different cat allergen components and its impact on type-2 biomarkers in young asthmatics.

Methods: The present thesis is based on the MIDAS asthma cohort, which includes asthmatics (n = 408) and healthy controls (n = 118), aged 10–35 years at baseline, with a follow-up visit 43{23-65} months later. All the subjects were characterized with regard to IgE sensitization, inflammation was assessed based on fractional exhaled NO (FeNO), blood eosinophil count (B-Eos) and other biomarkers, both type-2 and non-type 2, and lung function was evaluated with spirometry.

Results: FeNO and B-Eos maintained associations with clinical asthma outcomes in the IgE antibody concentration range 0.10–0.34 kUA/L, but not below 0.10 kUA/L. Non-atopic asthmatics with perceived cow’s milk hypersensitivity had poorer asthma-related quality of life than those with atopic asthma, and were characterized by clinically significant non-type 2 inflammation. Furthermore, longitudinal increase in height-adjusted FeNO associated independently with decline in lung function. IgE sensitization to cat lipocalins and/or cat serum albumin were independently associated with FeNO and B-Eos.

Conclusions: Our findings demonstrated that a cut-off of 0.10 kUA/L for IgE antibodies appeared to be useful for ruling out type-2 asthma in young subjects. A subgroup of non-atopic asthmatics was characterized by perceived cow’s milk hypersensitivity and non-type 2 inflammation. Longitudinal changes in FeNO associated with lung function decline in asthmatics. IgE sensitization to minor cat allergen components may promote both local and systemic type 2 inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 62
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1519
Keywords
Asthma phenotypes, IgE sensitization, atopy, cat allergen components, exhaled NO, airway hyper-responsiveness, lung function, asthma-related quality of life.
National Category
Respiratory Medicine and Allergy Pediatrics
Identifiers
urn:nbn:se:uu:diva-366892 (URN)978-91-513-0517-2 (ISBN)
Public defence
2019-01-29, Sal 42, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2018-12-28 Created: 2018-11-26 Last updated: 2019-01-09

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Tsolakis, NikolaosMalinovschi, AndreiNordvall, LennartJanson, ChristerBorres, Magnus PAlving, Kjell

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