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Relationship between longitudinal changes in type-2 inflammation and clinical outcomes in young asthmatics
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(English)Manuscript (preprint) (Other academic)
National Category
Pediatrics Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-366872OAI: oai:DiVA.org:uu-366872DiVA, id: diva2:1265894
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26
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: 2019-02-01

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