2012bafadhelmphd.pdf (3.07 MB)
The Use of Biomarkers to Explore Inflammation and Phenotypes during Exacerbations of Chronic Obstructive Pulmonary Disease
thesis
posted on 2012-12-19, 14:16 authored by Mona BafadhelExacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous. In particular the association of airway inflammation with pathogens during exacerbations of COPD remains largely unknown. The identification of biomarkers of COPD aims to characterise and phenotype COPD and COPD exacerbations, explore mechanisms of pathogenesis and provide decisions regarding targeted treatment strategies.
After validating the Meso scale discovery platform, biomarkers in stable state and during exacerbations COPD were explored. COPD exacerbations were associated with increased systemic and pulmonary inflammation and exacerbations associated with bacteria, virus and sputum eosinophils could be identified by sensitive and specific biomarkers. Multivariate statistical analysis identified independent biological exacerbations phenotypes and that these phenotypes could be predicted from stable state biomarkers. Finally a biomarker directed strategy using the peripheral blood eosinophil count to guide systemic corticosteroid therapy during exacerbations of COPD was effective, safe and identified phenotypes which have particular prognostic and therapeutic characteristics.
To conclude, biomarkers can define the heterogeneity of COPD and COPD exacerbations. The identification of COPD phenotypes can potentially move the management towards phenotype specific management and personalised medicine.
History
Supervisor(s)
Brightling, Christopher; Pavord, IanDate of award
2012-08-01Awarding institution
University of LeicesterQualification level
- Doctoral
Qualification name
- PhD