Periostin is a systemic biomarker of eosinophilic airway inflammation in asthma

Background: Eosinophilic airway inflammation is heterogeneous in asthma. We recently described a distinct subtype of asthma defined by the expression of genes inducible by Th2 cytokines in bronchial epithelium. This gene signature, which includes periostin, is present in approximately half of asthmatics, and correlates with eosinophilic airway inflammation. However, identification of this subtype depends on invasive airway sampling, hence non-invasive biomarkers of this phenotype are desirable. Objective: Identify systemic biomarkers of eosinophilic airway inflammation. Methods: We measured fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophil, periostin, YKL-40, and IgE levels and compared these biomarkers to airway eosinophilia in 5 cohorts of asthmatics across a range of severity (N=150). Results: We replicated our previous finding of a three-gene bronchial epithelial Th2 signature in a subset of asthmatics and found that peripheral blood periostin levels were highly correlated to the gene signature. Blood periostin is significantly elevated in asthmatics with evidence of eosinophilic airway inflammation relative to those with minimal eosinophilic airway inflammation despite inhaled corticosteroid (ICS) treatment across a range of disease severity. A logistic regression model including sex, age, body mass index (BMI), IgE, blood eosinophils, FeNO, and serum periostin in 59 severe asthmatics showed that, of these indices, serum periostin was the single best predictor of airway eosinophilia (p=0.007). Conclusions: Periostin is a systemic biomarker of airway eosinophilia in asthma and has potential utility in patient selection for emerging asthma therapeutics targeting Th2 inflammation.