Gomes, A. (2013) Chitinases and Periostin as novel biomarkers in Asthma. thesis, Medicine.
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Abstract
Rationale: Many asthmatic patients remain uncontrolled on conventional therapy. To individualize therapeutic approaches, asthma phenotypes need to be identified. Potential suitable circulating biomarkers include YKL-40 and periostin, which may represent bronchial remodeling and TH2 dependent asthma respectively. Methods: The ChAMP project aims to untangle the asthmatic syndrome by making enhanced use of previously executed studies. In this project, we selected two suitable studies of well-characterized mild asthmatic patients to examine the effects of allergen challenge and steroid treatment on YKL-40 and periostin, examined both in plasma and induced sputum by ELISA. Results: Plasma YKL-40 and periostin were unchanged following allergen challenge. Levels of sputum YKL-40 increased after high-dose allergen challenge (p<0.002), but not after repeated low-dose allergen challenge. Plasma periostin levels decreased after inhaled steroid treatment and repeated low-dose allergen challenge (p=0.0365). Sputum YKL-40 correlated with numbers of airway neutrophils (p=0.0010, rho=0.4936 (COX-2) and p=0.0025, rho=0.4824 (SMILDA)) and macrophages (p<0.0001, rho=0.6484 (SMILDA)). Conclusion: The different behaviors of these biomarkers in different biological matrices provide clues regarding pathophysiological mechanisms. Allergen challenge did not affect plasma YKL-40 and periostin, suggesting that these measurements do not reflect acute changes in airway milieu and may be more indicative of chronic disease processes. However, sputum measurements following allergen challenge show that YKL-40 in this matrix may mirror fibrotic/inflammatory processes, possibly due to its proximity to the airways. YKL-40 and periostin could help identify clinical phenotypes and the selection of suitable therapies. They could also prove useful targets for novel therapies.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Brinke, Dr. A. ten |
| Supervisor name: | Dahlén, Prof. S.E. and James, Anna and Middelveld, Roelinde and Karolinska Institute and Stockholm, Sweden |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:40 |
| Last Modified: | 25 Jun 2020 10:40 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/150 |
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