Respiratory failure, due to infection and concomitant inflammation is the major cause of morbidity and mortality in people suffering from the genetic disorder, cystic fibrosis (CF). Consequently, the CF Foundation currently estimates that patients with CF have a median predicted life expectancy of only 41.1 years. Understanding the relationship between the complex and diverse bacterial community present within the lower respiratory tract and patient outcomes has therefore become a top priority. Through the use of next generation sequencing technologies (Roche 454 and Illumina MiSeq) and ecological statistics and modelling, the complex relationships between the bacterial community within the CF lung and host related clinical factors were investigated. By first establishing guideline methodologies for the reduction of bias in the collection, storage and treatment of respiratory samples, this thesis aimed to use large scale spatial and longitudinal studies to investigate key relationships between the bacterial community and clinical factors. It has been well established that a complex and diverse bacterial community exists within the CF lung. Spatial sampling revealed key relationships between the bacterial community and other diagnostic parameters including, FEV1, gender, and clinic location. Longitudinal sampling aimed principally to investigate CF pulmonary exacerbations (CFPE), implicated in the progressive loss of lung function associated with CF lung disease. Over the course of a CFPE the common bacterial taxa show resistance to perturbations while the rare taxa show resilience. Through this investigation, Veillonella parvula was identified as a potential bioindicator of CFPE, introducing the potential for a rapidly testable parameter for clinicians to identify a CFPE. This finding could provide one of the most important recent developments in CF therapy.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:669584 |
| Date | January 2015 |
| Creators | Cuthbertson, Leah Forbes |
| Contributors | Bruce, Kenneth |
| Publisher | King's College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://kclpure.kcl.ac.uk/portal/en/theses/the-microbial-community-ecology-of-the-cystic-fibrosis-lung(7ae2ec94-0325-4d0c-93a3-449da53f6b1f).html |
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