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Title: Does airway pathology in severe preschool wheezers predict childhood asthma?
Author: O'Reilly, Ruth
ISNI:       0000 0004 2741 8087
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Although one third of all preschool children wheeze, only half of these will have persistent symptoms and go on to have asthma at school age. Pathological changes characteristic of asthma, including eosinophilic inflammation and increased reticular basement membrane thickness, were evident in endobronchial biopsies from severe recurrent wheezers aged 2-3 years when compared with age matched controls. However, at the time of endobronchial biopsy it was not known which children would persistently wheeze and develop asthma at school age. The work of this thesis follows up this group of children, both preschool wheezers (n=47) and non-wheezing controls (n=21), aged between 6-11 years and establishes the presence or absence of school age asthma, relating this to pre-school airway pathology. Children (n=51) were followed up at school age, and those who attended for the research visit (n=39) were characterised in terms of atopic status, lung function (spirometry, lung clearance index) and airway inflammation (exhaled nitric oxide) at school age. Forty percent (15/37) of preschool wheezers had developed asthma at school age. Although increased airway smooth muscle is an established pathological feature of asthma in school age children, nothing is known about airway smooth muscle in preschool wheezers, hence airway smooth muscle, smooth muscle mast cells and reticular basement membrane tenascin-C were measured in the endobronchial biopsies taken at preschool age. Next, airway remodelling (increased airway smooth muscle and increased reticular basement membrane thickness) and airway inflammation at preschool age were related to the presence or absence of asthma at school age. Sixty two percent (42/68) of children had one or more evaluable biopsies for airway smooth muscle assessment. Although reticular basement membrane thickness and submucosal eosinophils were significantly higher in preschool wheezers compared with controls, they did not discriminate the children who developed asthma by school age, suggesting these airway pathological features may be associated with current symptoms rather than future asthma risk. In contrast preschool airway smooth muscle was increased in those severe preschool wheezers who went on to develop school age asthma (n=8, median age 8.2 [6-10.4] years, median ASM 0.12 [0.08-0.16]) when compared with those who did not develop asthma (n=24, median age 7.3 [5.9-11] years, median ASM 0.07 [0.02-0.23]), p=0.007. These data suggest that future studies investigating the mechanisms underlying the persistence of preschool wheeze and its development to asthma should have a primary focus on airway smooth muscle.
Supervisor: Saglani, Sejal ; Bush, Andrew Sponsor: Asthma UK
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral