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

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.