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 TH2 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 FEV1, 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 TH2 inflammation.

Improving the diagnosis of eosinophilic asthma

“…This fits well with the observed correlation between periostin and specific IgE in sputum [45]. After this initial report, several investigators confirmed the association between periostin and sputum eosinophils, even proposed serum periostin as a biomarker for airway eosinophilia [42]. However, subsequent studies showed that the strength of the correlation between periostin and sputum eosinophilia, although significant, was relatively weak, and that neither serum nor sputum periostin was suitable for use as a surrogate marker of airway eosinophilia [43].…”

“…Several reports have shown significant correlations between periostin in serum and eosinophils in sputum [42,43]. Woodruff et al were the first to show upregulated periostin gene expression in bronchoalveolar lavage from patients with asthma as compared to normal control subjects, which was associated with increased concentrations of IL-4, IL-5, and IL-13 [44].…”

“…The cutoff values for blood eosinophils differ between 0.22 and 0.32 × 10 9 /L, for FeNO levels between 10 and 41 ppb, and for IgE 72 and 900 IU/mL [23]. For periostin, a value of 25-50 ng/mL or the median of the study population is mostly used [35,42,58]. These cutoff values are based on the optimal combination of sensitivity and specificity.…”

“…Threshold values with high sensitivity or high specificity to detect elevated sputum eosinophils have also been reported for FeNO [8,34,42,50,[66][67][68]. However, these thresholds vary widely depending on the technique that is being used, and the population under study.…”

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…In a post-hoc analysis, this antibody improved prebronchodilator FEV1 in the group with evidence for Th2 inflammation as measured by elevated serum periostin levels, a proposed surrogate marker of Th2 activity or FeNO [59,223]. Another anti-IL-13 antibody, tralokinumab, did not improve symptoms but resulted in a non-significant increase in FEV1 when compared to placebo in all comers.…”