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

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posted on 2019-11-13, 11:03 authored by Bethan L. Barker
Airway bacteria, airway inflammation, lung structure and skeletal muscle dysfunction
are all recognised as important components of chronic obstructive pulmonary disease
(COPD), yet the interplay between these components is not well understood.
Within this thesis I present an observational study exploring relationships between
airway inflammation and molecular measures of potentially pathogenic bacteria. I have
shown that airway bacterial detection is associated with increased airway inflammation
in stable COPD, and that this association appears to be driven by Haemophilus
influenzae.
I then present a cross-sectional and longitudinal study using dual energy x-ray
absorptiometry measurements of body composition and have shown that airway
bacterial load and inflammation are independent of body composition changes, and that
loss of skeletal muscle is not associated with accelerated airway inflammation or lung
function decline.
Within a multi-centre exacerbation cohort study I have shown that sputum bacterial load
is only weakly associated with quadriceps muscle strength in stable COPD. In addition
I have shown only a small, short-lived reduction in quadriceps strength at exacerbation,
suggesting that community managed exacerbations may have limited impact on long
term decline in muscle and physical function in COPD patients.
Finally, I present the results of a single centre study that has shown that air trapping
measured using quantitative computed tomography (QCT) makes the strongest unique
contribution to airflow obstruction in COPD. Moreover, H. influenzae bacterial load is
related to QCT measured small airways disease, and this association is independent of
the amount of neutrophilic airways inflammation.
In summary, within this thesis I provide data demonstrating significant relationships
between H. influenzae, airway inflammation and lung structural changes in COPD. By
contrast, my findings suggest that inflammation, and in particular overspill of
pulmonary inflammation is not a key pathophysiological mechanism leading to skeletal
muscle depletion or dysfunction in COPD.

History

Supervisor(s)

Christopher E. Brightling; Michael C. Steiner

Date of award

2017-06-27

Author affiliation

Department of Infection, Immunity and Inflammation

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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