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Title: The early development of COPD
Author: Allinson, James Peter
ISNI:       0000 0004 7969 8594
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Chronic Obstructive Pulmonary Disease (COPD) is a common, progressive disease responsible for substantial morbidity and mortality worldwide. However, current concepts of COPD are based upon studies of older individuals with already established disease leaving early stage COPD development relatively unstudied. This thesis explores potential early stage COPD development by analysing data collected across the life course of individuals within the National Survey of Health and Development. This thesis examines how the relationship between chronic mucus hypersecretion (CMH) and smoking develops with ageing and how CMH relates to both FEV1 decline during adulthood and airflow limitation in the seventh decade. This thesis also investigates how the impact of smoking upon adult lung function trajectory may be modified by early life exposures. This thesis demonstrates that CMH followed a dynamic course across life, strongly reflecting concurrent smoking behaviour, and that CMH duration reflected FEV1 loss. The relationship between smoking and CMH also evolved with ageing. CMH prevalence escalated among smokers between ages 36 and 43 years, consistent with increasing susceptibility to the effects of smoking, and at these ages CMH symptoms identified smokers more likely to have developed airflow limitation by age 60-64 years. This suggests that CMH is a biomarker of airway disease activity and that, during mid-life, CMH among smokers indicates an early phase of COPD development. This thesis also demonstrates that smoking interacts synergistically with infant exposures such that infant respiratory infection and infant poverty only impacted adult lung function among smokers. This is consistent with adolescent growth facilitating recovery from infant insults if catch-up growth is not impeded by smoking. This thesis provides new insights into how and when COPD may begin to develop. Further research investigating the pathophysiology accompanying CMH development during mid-life may reveal novel therapeutic targets to prevent the development of irreversible airway damage.
Supervisor: Wedzicha, Jadwiga ; Donaldson, Gavin Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral