Date of Award

2015

Document Type

Open Access Dissertation

Department

Epidemiology and Biostatistics

Sub-Department

Norman J. Arnold School of Public Health

First Advisor

Wilfried Karmaus

Abstract

Fetal origins of adult disease hypothesis states that adverse influences early in developmental period and particularly during intrauterine life can result in permanent changes in physiology which may lead to increased disease risk of chronic diseases in adulthood. Both fetal and adolescent period are critical time periods for development of lungs. Any adverse environmental exposures during these critical periods of lung growth is a form of programming which can have long term effects on pulmonary function. The purpose of this dissertation was to examine the association between different environmental exposures and pulmonary function in children and late adolescents. The first objective was to investigate the association between sensitization to house dust mites (HDM) allergen on skin prick test (SPT) and pulmonary function during late adolescence (18 years of age) within the birth cohort of Isle of Wight (IOW). The second objective was to assess the combined effects of maternal smoking during pregnancy and adolescent smoking on pulmonary function in late adolescence. This association was also tested in the birth cohort of IOW at 18 years of age. The third objective was to examine relationship between body burden of dichlorodiphenyl dichloroethene (DDE) and pulmonary function in pre-adolescent children (8-10 years of age) from federal state of Hesse, Germany.

The results from the first objective suggested that there exists an inverse dose response relationship between wheal diameter (immunological response obtained on SPT to HDM allergen) and pulmonary function parameters- forced expiratory volume in one second (FEV1), ratio of forced expiratory volume in one second over forced vital capacity (FEV1/FVC) and forced expiratory flow at 25-75% (FEF25-75%). Stratified analysis by history of asthmatic wheezing episodes showed reduced FEV1 and FVC in individuals with no history of asthmatic wheezing attacks.

For the second objective we found that the offspring of mothers who smoked during pregnancy are more likely to smoke during adolescence. Results showed that in girls maternal smoking during pregnancy and adolescent smoking had both independent and joint inverse effects on FEV1, FEV1/FVC ratio and FEF25-75% when compared with no exposure. Path analysis demonstrated that the effects of maternal smoking during pregnancy in girls were mediated through height, weight and adolescent smoking. In boys, adolescent smoking had direct inverse effect on FEV1/FVC ratio and effects of maternal smoking were mediated through its effects on adolescent smoking.

Results from the third objective demonstrated that DDE had crude inverse associations with height, weight, FEV1 and FVC in children of age 8-10 years. Further analysis showed that although DDE exposure did not affect pulmonary function directly in children, it had indirect effect on pulmonary function mediated through height and weight at age 8-10 years.

Children are particularly susceptible to environmentally induced lung diseases. All three environmental exposures studied in this dissertation showed adverse effects on pulmonary function during childhood and late adolescence. These findings indicated that the wheal diameter on SPT which is mostly used to determine sensitivity to HDM allergen could also serve has an indicator of underlying abnormal pulmonary function even in individuals without asthma symptoms. Second objective showed that exposure to gestational and adolescent smoking lead to reduced flow in mid as well as large airways. Adolescent girls were more vulnerable to smoking effects than boys. Finally, the use of path analysis improved the understanding of underlying directional or non-directional relationships between height, weight and DDE exposure on pulmonary function. These findings have implications in the areas of environmental epidemiology, respiratory epidemiology and child health epidemiology.

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