Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients - 29/08/12
, Richard W. Erickson, BS b, , David F. Choy, BS a, Sofia Mosesova, PhD c, Lawren C. Wu, PhD d, Owen D. Solberg, PhD f, g, Aarti Shikotra, BSc h, Richard Carter, MRCP h, Séverine Audusseau, MSc j, Qutayba Hamid, MD, PhD j, Peter Bradding, DM, FRCP h, i, John V. Fahy, MD, MSc f, g, Prescott G. Woodruff, MD, MPH f, g, Jeffrey M. Harris, MD, PhD e, Joseph R. Arron, MD, PhD a, ⁎ 
Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) Study Group‡
Corresponding author. Joseph R. Arron, MD, PhD, Genentech, Inc, ITGR Biomarker Discovery, Mail Stop 231C, 1 DNA Way, South San Francisco, CA 94080.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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, biomarker, sputum, bronchoscopy, eosinophil, TH2, IL-13, periostin, IgE, Feno
Abbreviations used : ACQ, BOBCAT, CV, Feno, ICS, POSTN, rhuPOSTN
Plan
| Supported by Genentech; by grants to J.V.F., P.G.W., P.B., and Q.H. from Genentech; National Institutes of Health (NIH) grants (HL56385, HL080414, and HL66564 to J.V.F. and HL097591 and HL095372 to P.G.W.); and the Sandler Asthma Basic Research Center (to J.V.F.). |
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| Disclosure of potential conflict of interest: G. Jia is employed by and has patents with Genentech. D. F. Choy is employed by, has received patents from, and has stock options in Genentech. S. Mosesova is employed by and has stock options in Genentech/Roche. L. C. Wu is employed by Genentech and holds equity in the Roche group. R. Carter has received research support from Genentech and has received travel expenses from Chiesi. S. Audusseau has received travel support for an investigator meeting. Q. Hamid has received research support from Meakins Christie Labs. P. Bradding has received research support from Genentech. J. V. Fahy has received grants from the National Heart, Lung, and Blood Institute and Boehringer Ingelheim; has received travel reimbursement from GlaxoSmithKline, Merck, Amgen, and the National Heart, Lung, and Blood Institute; is a member of the scientific Advisory Board for Cytokinetics; has consultant arrangements with Gilead, GlaxoSmithKline, Amgen, Portola Pharmaceuticals, Five Prime Therapeutics, and Merck; and is named inventor on a patent application for periostin as a biomarker in asthma. P. G. Woodruff has received research support from Genentech, is coinventor on a patent application related to periostin, is on the advisory board for Boehringer Ingelheim, and has received consultancy fees from MedImmune. J. M. Harris is employed by and has stock options in Genentech. J. R. Arron is employed by Genentech, has received payment for lectures from the American Asthma Association, has patents with Genentech, and has stock in Roche Holdings. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 130 - N° 3
P. 647 - septembre 2012 Retour au numéro
Article précédent
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