Fixed airflow obstruction relates to eosinophil activation in asthmatics.

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.

• Authors: Ida Mogensen, Kjell Alving, Sven-Erik Dahlen, Anna James, Bertil Forsberg, Junya Ono, Shoichiro Ohta, Per Venge, Magnus P Borres, Kenji Izuhara, Christer Janson, Andrei Malinovschi
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 49 Issue 2 Pg. 155-162 (02 2019) ISSN: 1365-2222 [Electronic] England
• PMID: 30365193 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

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

Topics

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