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Title: Influence of early life factors on later ventilatory function : interpreting associations with inflammation, cardiometabolic function and ethnicity
Author: Saad, Neil
ISNI:       0000 0004 7656 9367
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Poor ventilatory function, as measured by spirometry, is strongly related to mortality and is the primary characteristic of several chronic lung diseases. This thesis investigates the influence of early life factors, in particular birth weight, on later ventilatory function and elucidates the associations with inflammation, cardiometabolic function and ethnicity. First, I performed a systematic review and meta-analysis on birth weight and ventilatory function. The results provide strong evidence for a positive association of birth weight with forced vital capacity (FVC), a 59.4mL increase in FVC per kg increase in birth weight (95% CI: 43.3 to 75.5). Much weaker evidence was found to support a positive association of birth weight with the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC), particularly among children. Second, I investigated the association of cardiometabolic and inflammatory markers with FVC and FEV1/FVC in young adulthood in the Northern Finland 1966 birth cohort. The associations of inflammatory and cardiometabolic markers differed between FVC and FEV1/FVC, as well as by sex. These associations were strongly influenced by adjustment for important confounders (height and sex) and by mutual adjustment for inflammatory and cardiometabolic markers. These associations were not explained by their common link to low birth weight, nor by socio-economic factors, systemic inflammation or selected prenatal influences, suggesting the involvement of other environmental or genetic factors. Finally, I conducted a pilot investigation on ethnic differences in ventilatory function between White and South Asian British young adults. This study found a reduction of 860 mL (95% CI: -1320 to -400 mL) in FVC among South Asian British, identified parental immigration as an important predictor of FVC, and provided evidence against the hypotheses that differences in birth weight or trunk size can explain ethnic differences in ventilatory function. This study showed the feasibly of similar investigations in larger population-based studies.
Supervisor: Burney, Peter ; Minelli, Cosetta Sponsor: National Heart and Lung Institute Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral