By Marie Kragh MSc, PhD
Chariman: Ole Lund
Opponent: Dennis Sandris Nielsen
Opponent: Thomas Eiwegger
The prevalence of chronic inflammatory diseases in children, including childhood asthma, has increased during the past decades resulting in reduced quality of life for the implicated child and family, and an increased socioeconomic burden. Complex interactions between genetic factors (genetic predisposition) and the exposed environment, beginning as early as in perinatal life, are recognized causes of chronic inflammatory diseases.
This PhD thesis focuses on two potential environmental risk exposures for development of childhood asthma, namely maternal parity, and postpartum bacterial colonisation of the upper respiratory tract. The aim with this thesis was to investigate how maternal parity history affected neonatal immunity; and whether hereditary and environmental risk factors affected bacterial diversity in the upper respiratory tract of asymptomatic neonates. The study is based on clinical material from the birth cohorts of Copenhagen Prospective Studies on Asthma in Childhood (COPSAC).
The first study in the PhD thesis assessed how purified cord blood T cells from newborns of primiparous versus multiparous mothers react upon polyclonal activation in vitro. These data showed a reduced anti-inflammatory T cell function in first-born children as the IL-10 secretion and CD25 expression on CD4+ helper T cells were diminished as opposed to second- or later-born children. The result suggested that in utero T cell programing is responsible for this finding, which could be one of the explanations for the well-known epidemiological observations of enhanced risk for development of immune-mediated diseases in first-born children.
The second study assessed the associations between bacterial diversity and genetic predisposition for atopy and environmental risk factors relevant to establishment of a microbiota in the upper airways of newborns. The study showed a high diversity of nasopharyngeal bacterial in asymptomatic 1-month old infants. Moreover, season of birth was found to associate to nasopharyngeal bacterial diversity, with a higher bacterial diversity as well as specific bacteria profiles representing Gram-negative alphaproteobacteria and Gram-positive Bacilli in the nasopharynx of summer-born children. The result suggested that early postnatal colonization of the upper airways may reflect surrounding air at birth. A focus on the aspect of seasonality in modelling the impact of early dynamic changes in airway communities in relation to later disease development should be included in future studies. Overall, these findings contribute to our understanding of how common environmental factors, such as maternal parity and season of birth are associated to the development of the newborn’s immune system and nasal microbiota. These environmental factors tend to be overlooked both in the study design, statistical analysis and reporting of scientific studies. This may result in misinterpretations and errors in our search for causes of childhood asthma and other chronic inflammatory diseases.