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Fixed airflow obstruction relates to eosinophil activation in asthmatics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.ORCID iD: 0000-0002-0198-2718
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.ORCID iD: 0000-0003-0784-0443
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 2, p. 155-162Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO.

OBJECTIVES: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.

METHODS: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).

RESULTS: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06 (2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO.

CONCLUSIONS AND CLINICAL RELEVANCE: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO. This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

Place, publisher, year, edition, pages
2019. Vol. 49, no 2, p. 155-162
National Category
Medical and Health Sciences Immunology in the medical area
Research subject
Clinical Physiology
Identifiers
URN: urn:nbn:se:uu:diva-372784DOI: 10.1111/cea.13302ISI: 000457469600003PubMedID: 30365193OAI: oai:DiVA.org:uu-372784DiVA, id: diva2:1276825
Funder
Swedish Heart Lung FoundationSwedish Research CouncilVårdal FoundationStockholm County CouncilSwedish Asthma and Allergy AssociationSwedish Foundation for Strategic Research Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-03-08Bibliographically approved

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Mogensen, IdaAlving, KjellVenge, PerBorres, Magnus P.Janson, ChristerMalinovschi, Andrei

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Mogensen, IdaAlving, KjellVenge, PerBorres, Magnus P.Janson, ChristerMalinovschi, Andrei
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