Asthma and lower airway diseasePeriostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients
Section snippets
Patients' samples and microarray data
Microarray data and bronchial epithelial RNA from 42 nonsmoking patients with mild-to-moderate asthma were obtained from a previous study.13, 23 The Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) was a multicenter 3-visit study in which 67 subjects with severe asthma defined by an FEV1 of 40% to 80% of predicted value, an Asthma Control Questionnaire (ACQ) score of greater than 1.50 on 2 separate occasions, and a daily ICS dose of at least
Results
Our objective was to determine whether the bronchial epithelial TH2 signature associated with airway eosinophilia that we have described in patients with mild-to-moderate asthma not taking ICSs13 could be translated to a noninvasive biomarker of residual airway eosinophilia despite ICS treatment in patients with uncontrolled asthma.
Discussion
Although asthma is traditionally regarded as an allergic disease mediated by TH2-driven inflammation,1 there is emerging evidence of pathophysiologic heterogeneity.3, 4, 5, 6, 7, 8, 9, 10 We have recently shown that, in patients with mild-to-moderate asthma not undergoing steroid treatment, only about half the subjects have evidence of TH2 inflammation in their airways. The TH2-high subset is distinguished by increased markers of allergy, eosinophilic airway inflammation, bronchial fibrosis,
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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.).
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.
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These authors contributed equally to this work.
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For more information on the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma Study Group, see the acknowledgments section.