Wolthuis, Gerrit Ype (2026) Bronchial airway proteomics in COPD and hypercapnia. Master's Research Project 2, Biomedical Sciences.
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Abstract
This study characterized the bronchial airway proteome in COPD severity and hypercapnia using bronchial wash samples from two cohorts: SHERLOCk (cross-sectional; control, mild-moderate, and severe normocapnic COPD) and RECAPTURE (longitudinal; severe hypercapnic COPD undergoing NIV or standard care). LC-MS/MS proteomics was performed on 125 samples passing quality control, followed by upper-quartile normalization, half-minimum probabilistic imputation, and linear model-based differential abundance testing using limma in R. No proteins were significantly altered in mild-moderate COPD. In severe COPD, 226 proteins were significantly different compared to controls (222 depleted and 4 elevated) pointing to a possible broad loss of normal airway secretory and innate defence function. The most strongly depleted protein was carbonic anhydrase 6 (CA6), a novel finding with no prior COPD association. GO enrichment showed that the depleted proteins are mostly extracellular secreted proteins, with significant enrichment of the KEGG salivary secretion pathway. Elevation of the eosinophil granule proteins EPX and PRG2 indicated eosinophilic airway inflammation in a subset of patients. Comparing hypercapnic and normocapnic severe COPD identified nine significantly associated proteins. Three (S100A9, SAA2, and MPI) were specific to the hypercapnia comparison, with S100A9 and SAA2 suggesting heightened neutrophilic and acute-phase inflammation in hypercapnic disease.
| Item Type: | Thesis (Master's Research Project 2) |
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| Supervisor name: | Guryev, V. and Karp, T. |
| Degree programme: | Biomedical Sciences |
| Thesis type: | Master's Research Project 2 |
| Language: | English |
| Date Deposited: | 02 Sep 2026 08:02 |
| Last Modified: | 02 Sep 2026 08:02 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/37536 |
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