Aims: To measure symptomatic recovery over a year among an adult cohort recruited from hospital with community acquired pneumonia (CAP). To measure the host recovery mechanism efferocytosis and the diversity of the bacterial microbiota in sputum and relate these to individual characteristics of subjects in the cohort. Methods: Patients with CAP were recruited from two hospitals in Liverpool, (UK) and were followed-up for one year. The CAP-sym questionnaire was completed at multiple time-points in order to create a statistical model of symptomatic recovery. DNA was extracted from acute sputum samples and 16S rRNA sequencing revealed the diversity of bacteria in sputum. At one month into recovery subjects volunteered for bronchoalveolar lavage and rates of efferocytosis were measured by co-culturing ex-vivo alveolar macrophages with apoptotic autologous neutrophils. Results: The 169 subjects recruited with CAP were found to have high levels of socio-economic deprivation, smoking and COPD and the median age was 64 years. A non-linear, longitudinal, statistical model of symptoms found that smoking impaired recovery but people tended to describe better recovery as they got older. Efferocytosis was impaired by smoking but improved by statins and these effects were modified by body mass index. Those with prior pulmonary disease had lower bacterial diversity in their sputum and in this cohort a species from the genus Haemophilus was dominant. Conclusion: This work proves the principal that modelling CAP-sym scores can be used to investigate factors associated with differential recovery from CAP. It highlights the detrimental effects of smoking on both recovery and efferocytosis. This is the first study to show that the bacterial diversity of CAP sputum is influenced by prior lung disease. The translational outcomes are the potential for trials of statins as pro-recovery agents and to study modified empirical antibiotics for those with CAP and prior-lung disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677520 |
| Date | January 2015 |
| Creators | Wootton, Daniel |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://livrepository.liverpool.ac.uk/2028510/ |
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