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Title: Characterisation of exacerbations in non-CF bronchiectasis to establish endpoints in measuring treatment efficacy
Author: Sundaram, Supriya
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2013
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Bronchiectasis is characterised by chronic cough productive of mucopurulent sputum and frequent exacerbations. We have aimed to validate clinical, biochemical and microbiological endpoints to aid planning of future interventional studies. We recruited fifty-eight subjects with bronchiectasis at the Lung Defence unit (Papworth Hospital, Cambridge) and studied them in stable state (no exacerbation in the preceding four weeks) and during an exacerbation over a period of two years. The results of our research are discussed in this study. Clinical symptoms: Cough chest pain, chest discomfort, colour and volume of sputum and fatigue measured by a visual analogue score are useful endpoints. Breathlessness is a reliable endpoint when measured using either a visual analogue score or modified Borg’s breathlessness score. Health related quality of life measured using the Euroqol questionnaire is a sensitive marker of change during an exacerbation. The St George’s respiratory questionnaire did not demonstrate a significant change during an exacerbation. Spirometry: Forced expiratory volume in the first second (actual and percentage predicted) and Forced vital capacity (percentage predicted) do not change during the course of an exacerbation. Forced vital capacity actual may be used as an endpoint. pH of exhaled breath condensate in bronchiectasis is lower than in healthy subjects but does not change during the course of an exacerbation. Sputum appearance is a valid endpoint while 24hour volume of sputum and microbial clearance and anti-pseudomonal antibody titres cannot be used. ESR and serum titres of IFN-γ, TNF-α IL-6, IL-8, IL-10, IL-17 and IL-1β and titres in sputa of IFN-γ, IL-6, IL-17 do not change during an exacerbation. C-reactive protein and titres in sputa of TNF-α, IL-8 and IL-1β are effective indicators and can be recommended for use as end points in therapeutic interventional trials.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available