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Title: Influences of the environment on the development of neonatal allergic airways disease
Author: Vasiliou, Jessica Ellen
ISNI:       0000 0004 6348 0080
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Asthma is a chronic inflammatory airway disease and both environmental and genetic factors contribute to disease onset. As asthma predominantly develops during childhood it is important to investigate asthma pathogenesis in the context of the maturing immune system and developing lung. A neonatal house dust mite (HDM)-induced model of allergic airways disease (AAD) was used to assess the impact of age, diet, pollution and maternal allergy on the development of neonatal AAD. To investigate the effect of age, age at first allergen challenge was altered. Allergen exposure during the first week of life caused robust AAD, but exposure between 14-21 days resulted in a hyporesponsiveness phenotype. This period corresponded to a nadir in pulmonary interleukin (IL)-13 producing T cells and innate lymphoid type 2 (ILC2) cells. Maternal asthma is a risk factor for the development of childhood asthma. HDM exposed offspring born to allergic mothers had reduced airway compliance 8 weeks of age and mounted a faster IgE response than offspring from non-allergic mothers. Serum vitamin D levels have been correlated with asthma control in adults and children. Vitamin D insufficiency in utero resulted in pulmonary Th2-skewing and a decrease in T regulatory cells irrespective of HDM or PBS exposure. Restoration of vitamin D reduced eosinophilia and IgE levels in HDM exposed mice. Increased air pollution has been correlated with asthma exacerbations. Exposure of pregnant female mice to diesel exhaust particles resulted in increased inflammation in the lungs of offspring, but did not exacerbate AAD. The data presented in this thesis strongly support a case for in utero and early life exposures as a crucial determinant in immune programming in early life, with likely additional influences on lung development.
Supervisor: Lloyd, Clare ; Saglani, Sejal ; Hawrylowicz, Kasia Sponsor: Asthma UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral