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Fixed airflow obstruction relates to eosinophil activation in asthmatics.
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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, e.g., fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodeling, 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: 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 centers. 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. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. Vol. 49, no 2, p. 155-162
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Occupational Health and Environmental Health
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URN: urn:nbn:se:umu:diva-152938DOI: 10.1111/cea.13302ISI: 000457469600003PubMedID: 30365193OAI: oai:DiVA.org:umu-152938DiVA, id: diva2:1259679
Funder
Swedish Heart Lung FoundationSwedish Research CouncilStockholm County CouncilSwedish Asthma and Allergy AssociationSwedish Foundation for Strategic Research Available from: 2018-10-30 Created: 2018-10-30 Last updated: 2019-02-22Bibliographically approved

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Forsberg, Bertil

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