Disconnect of type 2 biomarkers in severe asthma; dominated by FeNO as a predictor of exacerbations and periostin as predictor of reduced lung function

Respir Med. 2018 Oct:143:31-38. doi: 10.1016/j.rmed.2018.08.005. Epub 2018 Aug 9.

Abstract

Background: biomarkers of Type 2 (T2) inflammation may predict asthma control and exacerbation risk. However, the relationships between individual T2 biomarkers to exacerbations and lung function in severe asthma remain uncertain.

Objectives: to explore the roles played by T2 biomarkers individually and as a composite score in predicting clinical outcomes in severe asthma.

Methods: unselected severe asthma patients were enrolled in this cross sectional real life study. Participants were clinically characterised and the following measurements were obtained: the frequency of exacerbations requiring oral corticosteroids (OCS), asthma control (Juniper ACQ6-7), lung function, Fraction exhaled Nitric Oxide (FeNO), peripheral blood eosinophils (PBE), and serum periostin.

Results: A total of 115 patients were recruited [mean age 45 years (range 18-70), 80 (69.6%) females, mean forced expiratory volume in first second (FEV1) %predicted was 68% ± 24.7, mean inhaled corticosteroids (ICS) 1.96 ± 0.82 mg/day. FeNO correlated significantly with PBE (r = 0.35, p = 0.0004), but not with periostin (r = 0.22, p = 0.065) and there was no significant correlation between PBE and periostin. FeNO correlation with exacerbations (r = 0.42, p = 0.0008) was stronger than PBE and periostin. A composite score of the 3 biomarkers correlated with exacerbations in a dose-dependent manner but multiple regression analysis did not confirm an added benefit. Only periostin demonstrated a significant correlation with FEV1%predicted (r = -0.34, p = 0.004) with ROC-AUC 0.7.

Conclusion: FeNO demonstrated stronger correlation with asthma exacerbations than PBE or periostin with no definite added benefit from a composite score of the 3 biomarkers. Only periostin showed significant association with reduced lung function raising its potential as a biomarker of airway remodeling.

Keywords: Asthma control; Blood eosinophils; Exacerbations; FeNO; Lung function; Periostin; Severe asthma; Type 2 inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / diagnosis*
  • Asthma / physiopathology
  • Biomarkers / analysis
  • Biomarkers / blood
  • Breath Tests
  • Cross-Sectional Studies
  • Disease Progression
  • Eosinophils
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Nitric Oxide / analysis*
  • Predictive Value of Tests
  • Respiratory Function Tests
  • Severity of Illness Index
  • Young Adult

Substances

  • Biomarkers
  • Nitric Oxide