Fixed airflow obstruction relates to eosinophil activation in asthmatics

Clin Exp Allergy. 2019 Feb;49(2):155-162. doi: 10.1111/cea.13302. Epub 2018 Nov 25.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma* / blood
  • Asthma* / pathology
  • Biomarkers / blood
  • Biomarkers / urine
  • Cell Adhesion Molecules / blood
  • Cross-Sectional Studies
  • Eosinophil Cationic Protein / blood
  • Eosinophil-Derived Neurotoxin / urine
  • Eosinophils / metabolism*
  • Eosinophils / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Pulmonary Disease, Chronic Obstructive* / blood
  • Pulmonary Disease, Chronic Obstructive* / pathology
  • Pulmonary Disease, Chronic Obstructive* / urine
  • Spirometry

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • POSTN protein, human
  • Nitric Oxide
  • Eosinophil-Derived Neurotoxin
  • Eosinophil Cationic Protein