Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality and morbidity worldwide. COPD is a complex and heterogeneous disease that exhibits a wide range of clinical phenotypes and it is characterised by numerous pulmonary and extra-pulmonary manifestations. Despite the rising incidence, prevalence and burden associated with COPD, the condition remains underdiagnosed and undertreated. There is a clear and urgent need for the development of diagnostic and disease management strategies that account for COPD heterogeneity. Tremendous efforts have been made in the field of biomedicine for the discovery of biomarkers that reflect disease activity; however, the clinical translation and implementation of these biomarkers have not matched those efforts. This study attempted to identify the most promising combination of biomarkers for the diagnosis and monitoring of COPD by employing functional genomics and next generation sequencing approaches on sputum. Many protein biomarkers that reflect the pathophysiology of COPD occurring with the onset and development of the disease have been identified. Additionally, a number of clinical phenotypes of COPD driven by variables such as body mass index, smoking status and treatment with oral steroids have been elucidated. Differences in the total microbial load, communities’ richness and evenness appear to fluctuate at both genera and phyla level in relation to the onset, progression and disease stability. Lastly, differences in the proteins of microbial species provide insights into the pathology of COPD characteristic of every stage of the disease. The implementation of those biomarkers in clinical practice shows the most sustainable avenue for diagnosing and monitoring COPD. The impact associated with the translation of these findings could be linked to a decrease in the figures associated with COPD-driven mortality and morbidity, increased survival, improved quality of life and better patient outcomes.
|Date of Award||2020|
|Supervisor||Luis Mur (Supervisor) & Russ Morphew (Supervisor)|