As one-third of preschool wheeze (PSW) children progress to school-age asthma, the early-life period (1- 3 years old) offers a window of opportunity to better characterise the immune profile of preschool wheezers that may progress to school-aged asthma.
The aim of this thesis was to phenotype the immune heterogeneity of paediatric airways disease. In doing so, it was hypothesised that children with severe PSW have a distinct airway and blood immune cell profile compared to non-wheezing disease controls. Obtaining optimal airway samples from young children remains challenging. Thus, a complex multiparameter spectral cytometry approach measuring 34-parameters was developed using adult bronchoalveolar lavage (BAL) and blood samples, to determine the cellular phenotype of most immune cell subsets. This showed the technique could be used for both conventional analysis of immune cell populations or unbiased clustering.
Conventional analysis revealed that PSWs had several distinct immune phenotypes compared to children with lower respiratory tract infections (LRTI) and severe therapy-resistant asthma (STRA). PSWs displayed reduced airway CD8+ CD25+ CD127- T cells compared to LRTIs. Additionally, circulating CD15+ neutrophils and CD14+ CD16- classical monocytes were decreased in PSWs relative to LRTIs. There was a notable positive correlation between peripheral CD14+ CD16- cells and the number of bacterial infections in children with PSW. Furthermore, CD4+ CD25+ CD127- T cells were markedly reduced in PSWs blood compared to both STRA and LRTIs...