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

被引:535
作者
Jia, Guiquan [1 ]
Erickson, Richard W. [2 ]
Choy, David F. [1 ]
Mosesova, Sofia [3 ]
Wu, Lawren C. [4 ]
Solberg, Owen D. [6 ,7 ]
Shikotra, Aarti [8 ]
Carter, Richard [8 ]
Audusseau, Severine [10 ]
Hamid, Qutayba [10 ]
Bradding, Peter [8 ,9 ]
Fahy, John V. [6 ,7 ]
Woodruff, Prescott G. [6 ,7 ]
Harris, Jeffrey M. [5 ]
Arron, Joseph R. [1 ]
机构
[1] Genentech Inc, ITGR Biomarker Discovery, San Francisco, CA 94080 USA
[2] Genentech Inc, Bioanalyt Res & Dev, San Francisco, CA 94080 USA
[3] Genentech Inc, Dept Biostat, San Francisco, CA 94080 USA
[4] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA
[5] Genentech Inc, ITGR Early Clin Dev, San Francisco, CA 94080 USA
[6] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA
[7] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[8] Univ Leicester, Univ Hosp Leicester NHS Trust, Glenfield Hosp, Leicester LE1 7RH, Leics, England
[9] Univ Leicester, Inst Lung Hlth, Dept Infect Immun & Inflammat, Leicester LE1 7RH, Leics, England
[10] McGill Univ, Meakins Christie Labs, Fac Med, Montreal, PQ, Canada
基金
美国国家卫生研究院;
关键词
Asthma; biomarker; sputum; bronchoscopy; eosinophil; T(H)2; IL-13; periostin; IgE; FENO; EXHALED NITRIC-OXIDE; CELL ADHESION MOLECULE; GENE-EXPRESSION; MONOCLONAL-ANTIBODIES; PROGNOSTIC MARKER; IL-13; EXPRESSION; LUNG; SPUTUM; EXACERBATIONS; MEPOLIZUMAB;
D O I
10.1016/j.jaci.2012.06.025
中图分类号
R392 [医学免疫学];
学科分类号
100108 [医学免疫学];
摘要
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 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 T(H)2 inflammation. (J Allergy Clin Immunol 2012;130:647-54.)
引用
收藏
页码:647 / +
页数:18
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