Fixed airflow obstruction relates to eosinophil activation in asthmatics

Summary 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 ( FEV 1 ) over forced vital capacity ( FVC ) being below the lower limit of normal ( LLN ). The following type 2 inflammation markers were assessed: exhaled nitric oxide (Fe NO ), 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 Fe NO 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.