AN EPIDEMIOLOGICAL APPROACH TO COMORBIDITIES IN PATIENTS WITH COPD

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is associated with comorbidities. Cardiovascular (CV) disease, cognitive impairment, dementia, and depression are common comorbidities in patients with COPD, leading to increased morbidity and mortality. However, there are considerable gaps in how these comorbidities are assessed, while the burden of others remains inadequately researched. This PhD applied several methodologies and used different databases to 1) explore whether circulating biomarkers from the blood (soluble Receptor for Advanced Glycation End-products - sRAGE) and urine (microalbuminuria) might have a role in COPD related to prognostication of CV risk (assessed by aortic stiffness and carotid intima-media thickness), 2) evaluate the prevalence and incidence of cognitive impairment and dementia, 3) examine the incident risk of depression, and 4) assess the risks of respiratory-related morbidities associated with antidepressant use in patients with COPD. Using data from a multisite UK study, sRAGE was not associated with aortic stiffness, carotid intima-media thickness, or CV disease in patients with COPD. However, there was a weak direct association between sRAGE and spirometric lung function measures. Data from the same cohort also showed that urinary albumin creatinine ratio (UACR) was not strongly associated with physiological CV risk measures. Nevertheless, patients with COPD and either diabetes, ischaemic heart disease, or cerebrovascular disease have increased UACR, compared to patients without these comorbidities. Microalbuminuria was also prevalent in all patients with COPD. Using a large primary care database, this PhD demonstrates that patients with COPD have increased prevalence of cognitive impairment compared to subjects withoutIII COPD, matched by age, gender and GP surgery. The incidence of cognitive impairment following COPD diagnosis was 23.1 per 1,000 person-years compared to 16.3 per 1,000 person-years in subjects without COPD. However, the prevalence and incidence of dementia were less frequently recorded in patients with COPD compared to individuals without COPD, indicating the possibility of underdiagnosis of dementia and highlighting the need for systematic assessment. The incidence of depression was also greater following COPD diagnosis, compared to subjects without COPD, which indicates the need to stay alert and target accordingly. Antidepressant use was associated with increased risks of pneumonia and COPD exacerbations relative to periods of unexposed to antidepressants in patients with COPD, raising the concern of potential side-effects and adverse events. This thesis addresses several aspects of COPD comorbidities and contributes new evidence for assessing, recognising, and managing comorbidities in patients with COPD.