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Palser, Sally C. (2024) Mitigating the harm caused by Pseudomonas aeruginosa in Cystic Fibrosis. PhD thesis, University of Nottingham.

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Abstract

Cystic fibrosis (CF) affects up to 100,000 people worldwide. Defects in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene cause abnormally viscid secretions at epithelial surfaces. In the lungs the abnormal secretions reduce clearance of both pathogens and sputum, predisposing to recurrent lung infections. Ultimately recurrent infections can cause respiratory failure and death.

Pseudomonas aeruginosa is a major cause of pulmonary infections and morbidity in CF. Preventing infection with P. aeruginosa is, therefore, an important goal in maintaining good health in people with CF. The source of most infection is unclear, though in some cases is through person-to-person spread.

Once infection has occurred eradication therapy can be used to delay the onset of chronic infection. People with CF chronically infected with P. aeruginosa are exposed to additional treatment to suppress the organism and treat additional pulmonary exacerbations. They are therefore at risk of additional side effects. Aminoglycoside antibiotics, commonly used in the treatment of pseudomonal infection, cause ototoxicity as one of their major side effects.

This thesis will aim to understand the additional harms caused by P. aeruginosa in CF, over and above direct pulmonary damage. In addition it will examine strategies which may help mitigate these harms.

The first study qualitatively examined how the CF community feels about P. aeruginosa. This identified significant, negative emotional impact on both patients and families. One identified theme was the fear engendered by the lack of knowledge about the source if infection and how it can be prevented.

The second study therefore, systematically reviewed the evidence for strategies to prevent initial infection. The only strategies which were found to be potentially successful were CFTR modulator therapy, vaccination against P. aeruginosa and cohort segregation.

Since prevention is challenging the third study systematically reviewed strategies to delay recurrence of infection after eradication. Only a single study was included but gave moderately good evidence that cycled antibiotic therapy delays recurrence of P. aeruginosa infection.

Finally, the utility of a novel hearing test, the High Frequency Digit Triplet test, was assessed in adults and adolescents with CF, when well and unwell, and in children. Testing was feasible but the test was insufficiently sensitive and specific to be used as a screening tool.

In this thesis I have shown additional ways in which P. aeruginosa can cause harm in CF and found some strategies which may help ameliorate this harm. The need for internationally recognised definitions surrounding P. aeruginosa infection and hearing loss were highlighted.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Smyth, Alan R. Ferguson, Melanie A.
Keywords:	Cystic Fibrosis; Pseudomonas aeruginosa; Ototoxicity; Hearing loss; Patient and public involvement
Subjects:	W Medicine and related subjects (NLM Classification) > WF Respiratory system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	77908
Depositing User:	Palser, Sally
Date Deposited:	17 Jul 2024 04:40
Last Modified:	17 Jul 2024 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/77908

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