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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.