Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients

Abstract

Background: Eosinophilic airway inflammation is heterogeneous in asthmatic patients. We recently described a distinct subtype of asthma defined by the expression of genes inducible by T(H)2 cytokines in bronchial epithelium. This gene signature, which includes periostin, is present in approximately half of asthmatic patients and correlates with eosinophilic airway inflammation. However, identification of this subtype depends on invasive airway sampling, and hence noninvasive biomarkers of this phenotype are desirable.

Objective: We sought to identify systemic biomarkers of eosinophilic airway inflammation in asthmatic patients.

Methods: We measured fraction of exhaled nitric oxide (Feno), peripheral blood eosinophil, periostin, YKL-40, and IgE levels and compared these biomarkers with airway eosinophilia in asthmatic patients.

Results: We collected sputum, performed bronchoscopy, and matched peripheral blood samples from 67 asthmatic patients who remained symptomatic despite maximal inhaled corticosteroid treatment (mean FEV(1), 60% of predicted value; mean Asthma Control Questionnaire [ACQ] score, 2.7). Serum periostin levels are significantly increased in asthmatic patients with evidence of eosinophilic airway inflammation relative to those with minimal eosinophilic airway inflammation. A logistic regression model, including sex, age, body mass index, IgE levels, blood eosinophil numbers, Feno levels, and serum periostin levels, in 59 patients with severe asthma showed that, of these indices, the serum periostin level was the single best predictor of airway eosinophilia (P = .007).

Conclusion: Periostin is a systemic biomarker of airway eosinophilia in asthmatic patients and has potential utility in patient selection for emerging asthma therapeutics targeting T(H)2 inflammation.

FIG 1

BOBCAT study schema.

FIG 2

Peripheral blood periostin levels differentiate patients with severe uncontrolled asthma taking high-dose ICSs according to airway eosinophilic inflammation. A, Dichotomized by sputum eosinophilia. B, Dichotomized by tissue eosinophilia. C, Sputum versus biopsy specimen eosinophilia. D, Composite airway eosinophil score demonstrating a strong positive progression of increasing serum periostin levels with increasing scores (P = .002, logistic regression). Bx, Biopsy.

FIG 3

Sensitivity of biomarkers for eosinophilic airway inflammation. A, Probability of composite eosinophil status = “high” as a function of serum periostin. Dashed lines denote 95% CIs. B, Receiver operating characteristic curve analysis of the sensitivity and specificity of serum periostin, Feno, and serum IgE levels and blood eosinophil numbers for composite airway eosinophil status. AUC, Area under the curve.