Clinical and microbiological endpoints in chronic airway diseases

Determining how bacterial load and community composition changes with time may improve our understanding of the natural history of these chronic airway diseases. <br>The aims of this thesis were to (i) to determine the psychometric properties of HR Qol questionnaires in bronchiectasis, (ii) to measure the longitudinal change in bacterial load and community composition inpatients with bronchiectasis when clinically stable and following antibiotic treatment of a PEx, (iii) to determine the antimicrobial susceptibility of P.aeruginosa and H. influenzae isolates cultured from sputum samples collected from patients with bronchiectasis and (iv) to determine changes in total bacterial and P. aeruginosa load following antibiotic treatment of a PEx in people with CF who received either microbiome directed or empirical antibiotic treatment. <br>Results showed that all HRQol questionnaires had good internal consistency and short-termtest-retest reliability in at least some domains.

Responsiveness was reasonable with the meta-analysis showing a difference between the treatment and placebo effect. In people with bronchiectasis, no statistical difference was apparent in total bacterial, P. aeruginosa and H. influenzae load and microbiome composition during periods of clinical stability and following antibiotic treatment of aPEx. However, P. aeruginosa load was associated with lower lung function and H.influenzae load was associated with increased systemic inflammation .P.aeruginosa isolates were susceptible to tobramycin, ceftazidime and ciprofloxacin, while H. influenzae isolates were susceptible to ampicillin, ciprofloxacin and co-amoxiclav but resistant to azithromycin.