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Title: Studies on the assessment and management of chronic obstructive pulmonary disease
Author: Calverley, Peter M. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2013
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Chronic obstructive pulmonary disease (COPD) has been and remains a major cause of morbidity and mortality across the world. The studies reported in this thesis describe some of the important concepts which have been tested and translated into routine clinical practice in the last 3 decades. We have now clarified the reflex mechanisms underlying persistent cough in COPD, defined the non-specific nature of the sensation of breathlessness in COPD and established that sleep quality is poor in hypoxaemic patients. Secondary polycythaemia is strongly related to carbon monoxide exposure from cigarettes which can also impair exercise tolerance. However the principal reason for exercise limitation in COPD patients is dynamic hyperinflation together with the response of the chest wall muscles to changing lung volume. Defining bronchodilator responsive patients is difficult as the chance of being classified as a responder varies with random fluctuations in baseline FE\A. Expiratory flow limitation at rest is a useful descriptive variable in characterising COPD but is not a predictor of response to bronchodilator drugs. COPD exacerbations are still defined by symptom change which does not always agree with the use of therapy, the commonest outcome reported in clinical trials. However events defined by health care use show a consistent pattern over time and patients who exacerbate often in one year are highly likely to do so in subsequently. Exacerbations are associated with worsening lung mechanics and increased operating lung volume which decreases as the episode resolves. Oral corticosteroids hasten the resolution of these episodes. However hyperglycaemia in patients with respiratory failure is a poor prognostic sign despite non-invasive ventilation. Long-acting inhaled bronchodilators like tiotropium have a sustained bronchodilator effect over the 24 hour day but this does not abolish the normal circadian variation in lung function. Anti-inflammatory therapy with inhaled corticosteroids can reduce exacerbation numbers and improve health status. An effect on mortality has not been conclusively established but seems possible while all treatments so far tested which ameliorate symptoms and reduce exacerbations seem to modify decline in lung function. Another anti-inflammatory agent the PDEIV inhibitor roflumilast has similar effects on exacerbation rate and lung function and may be additive in action. Other non-medical therapy such as heliox can substantially increase exercise performance but are not yet practical for routine use. Rehabilitation, by contrast, can dramatically improve exercise capacity without changing daily activity levels. Despite concerns to the contrary all existing drug treatment is well tolerated and safe. Future studies will need to address earlier intervention not only with smoking cessation -a key intervention of itself- but also with other probably anti-inflammatory therapy which can prevent disease progression and potentially limit the development of co-morbidities. Improvement in patients with more established disease is more likely to follow from the better delivery of the therapy we already possess rather than reversing well established pathology which remains a distant goal at present.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available