Exploring the interplay between airway bacteria, airway inflammation, lung structure and skeletal muscle dysfunction in COPD

<div>Airway bacteria, airway inflammation, lung structure and skeletal muscle dysfunction</div><div>are all recognised as important components of chronic obstructive pulmonary disease</div><div>(COPD), yet the interplay between these components is not well understood.</div><div>Within this thesis I present an observational study exploring relationships between</div><div>airway inflammation and molecular measures of potentially pathogenic bacteria. I have</div><div>shown that airway bacterial detection is associated with increased airway inflammation</div><div>in stable COPD, and that this association appears to be driven by Haemophilus</div><div>influenzae.</div><div>I then present a cross-sectional and longitudinal study using dual energy x-ray</div><div>absorptiometry measurements of body composition and have shown that airway</div><div>bacterial load and inflammation are independent of body composition changes, and that</div><div>loss of skeletal muscle is not associated with accelerated airway inflammation or lung</div><div>function decline.</div><div>Within a multi-centre exacerbation cohort study I have shown that sputum bacterial load</div><div>is only weakly associated with quadriceps muscle strength in stable COPD. In addition</div><div>I have shown only a small, short-lived reduction in quadriceps strength at exacerbation,</div><div>suggesting that community managed exacerbations may have limited impact on long</div><div>term decline in muscle and physical function in COPD patients.</div><div>Finally, I present the results of a single centre study that has shown that air trapping</div><div>measured using quantitative computed tomography (QCT) makes the strongest unique</div><div>contribution to airflow obstruction in COPD. Moreover, H. influenzae bacterial load is</div><div>related to QCT measured small airways disease, and this association is independent of</div><div>the amount of neutrophilic airways inflammation.</div><div>In summary, within this thesis I provide data demonstrating significant relationships</div><div>between H. influenzae, airway inflammation and lung structural changes in COPD. By</div><div>contrast, my findings suggest that inflammation, and in particular overspill of</div><div>pulmonary inflammation is not a key pathophysiological mechanism leading to skeletal</div><div>muscle depletion or dysfunction in COPD.</div>