Electronic Theses and Dissertations

Date

2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Public Health

Committee Chair

Wilfried Karmaus

Committee Member

Yu Jiang

Committee Member

Hongmei Zhang

Committee Member

Syed Hasan Arshad

Abstract

Asthma and wheezing present public health changes that manifest during early childhood. This dissertation utilizes longitudinal data within the Isle of Wight Birth Cohort (IOWBC) third generation to explore the development of early childhood wheezing phenotypes, their implications for asthma development, including environmental and epigenetic factors. Children in the F2-generation (n=611) of the IOWBC were followed-up at 3, 6, 12, 24, 36, and 72 months, and the incidence of wheeze subtype (general, infectious, and non-infectious) were used in group-based trajectory models to identify phenotypes of early childhood wheezing. These trajectories were examined as predictors of asthma diagnosis, lung function, and allergic sensitization. Further, this investigation assessed the association of these phenotypes with epigenetic markers at birth and maternal and offspring characteristics to bridge a gap in knowledge from maternal characteristics to at birth epigenetics to clinical manifestations of wheezing to later asthma diagnosis. These analyses identified ten 36-month trajectories of wheeze across the three wheezing subtypes. All subtypes have trajectories describing “Infrequent/Never” wheezing. Further, “Persistent” trajectories were present for general and infectious wheeze subtypes. “Persistent” general wheeze (OR: 13.11, 95% CI: 1.35-127.57) was found to be significantly associated with asthma. Epigenetic analysis identified 159 CpG sites associated with 72-month phenotypes of wheeze. Through confirmatory replication steps, seventeen sites were identified as most strongly associated with early childhood wheezing phenotypes. The maternal characteristics of gestational BMI and maternal history of asthma were significantly associated with offspring 72-month wheeze phenotypes. Maternal use of atopic management medications was not associated with increased offspring risk of asthma. Moreover, higher birth order was associated with increased wheezing. Importantly, maternal and offspring characteristics were associated with increased offspring wheezing, but not with offspring asthma diagnosis at or after 72 months. This identification of wheezing phenotypes distinguished by wheeze subtype reveals previously undescribed patterns of wheeze within the context of early childhood asthma development. Moreover, this dissertation links those phenotypes to epigenetic markers, maternal characteristics, and offspring characteristics. These findings offer insight for future studies to validate the associations identified and further explore the epigenetic, biological, genetic, and clinical significance of the identified factors.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Open Access

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