Mechanisms and Impact of Bacterial Colonisation in COPD

Overview

COPD is a leading cause of lung disease and a common cause of hospitalisation, time off work and death. Smoking is the major factor associated with development of COPD. Nevertheless why some people develop COPD while others, including many smokers do not, is poorly understood. A central feature of COPD is accumulation of a particular type of white blood cell, the neutrophil, which is a key component in defence against bacterial infection in the lung airway. As disease progresses the small airways of many patients with COPD start to accumulate bacteria, which are normally lacking in the small airways of healthy individuals or smokers who lack COPD. The accumulation of bacteria in the smaller airways of many patients with COPD may be important to the development of the disease. Researchers will test if blood cells, which normally ingest and kill bacteria, have a reduced ability to perform this function in patients with COPD and whether the clearance of these blood cells after they have performed their role in protecting against infection is impaired. Researchers will relate these findings to the clinical features of COPD in a well-defined group of patients who have had extensive characterisation of their disease. In particular, researchers will relate this defect to the presence of frequent flares of disease, which lead to symptoms of wheezing and shortness of breath. Comparison will be made between blood cells obtained from the lung and from he blood to determine if the alterations are specific to the lung. Researchers will identify particular molecular alterations in the way these blood cells respond to bacteria and determine whether they can correct these alterations using agents, which are used to treat a range of different medical conditions, but which they predict might correct these alterations in function. The aim of this programme of work is ultimately to identify new ways in which to treat COPD and the agents, which the researchers demonstrate have the greatest potential to correct the abnormalities in cell function of patients with COPD, would in the future be studied in clinical trials.

Work package one involves the consolidation and further characterisation of a number of pre-existing UK-based clinical cohorts of patients with COPD. This involves collection of epidemiological and physiological data from patients and controls to enable a complete definition of disease phenotype. Work package two will examine microbiological and innate immune parameters in this cohort to define whether innate immune defects underpin the susceptibility to infectious exacerbation and progression of airways disease. It will perform microbiological characterisation of each group and will look at the behaviour of groups who have frequent infectious exacerbations of disease as compared to those that do not. Work package three will measure lung injury and work package four will define physiological characteristics including chest wall muscle function in the cohort. Our work will sit within work package two. Researchers will collect data from patients within the cohort and in patients whom they may recruit locally and add to the cohort. Researchers will also share samples with other work packages (academic and industry based collaborators) as required to enable correlation of our findings with other investigators in our work package or other work packages. This project, which sits within work-package two will measure the capacity of primary phagocytes (neutrophils, monocytes and macrophages) isolated from COPD patients' blood or alveolar macrophages isolated from patients' lungs to carry out key host defence functions and compare these to similar cells isolated from age and sex-matched non-smokers or smokers without COPD as controls.