Exploring the relationship between obstructive sleep apnoea, asthma and atopic disease in children
Creators: name: Grime, Christopher John
Publisher: name: Imperial College London
Year: 2017

description: OSA in children is now recognised as a common health problem with an estimated prevalence of up to 5.7% and an associated with delayed growth and development, cardiovascular consequences and metabolic disorders. The role that CD4+ T-cells play in the pathology has been demonstrated with higher peripheral Th17 and lower Treg cell counts in adults and children with confirmed OSA suggesting a T-cell driven inflammatory basis to the underlying pathology. Links have therefore been proposed between OSA and other inflammatory disorders involving T-cells such as asthma and atopic disease. An OSA incidence of 63% has been reported in ‘poorly controlled’ asthmatics with improvement in asthma control following adenotonsillectomy. The current published literature however lacks sleep study confirmation of OSA plus well-defined evidence of asthma and atopy to really explore the relationship. I hypothesised that the incidence of OSA in children with Severe Therapy Resistant Asthma would be higher than reported as the background incidence in childhood and that there would be a higher prevalence of atopy in children with sleep study proven OSA undergoing adenotonsillectomy compared to those without OSA. I also hypothesised that the tonsils tissue in child with OSA would contain more Th17 cells, Less Treg cells and have a Th2 and ILC2 phenotype compare to the tonsils of children without OSA. All children defined as severe therapy resistant asthmatics (STRA) from September 2013 – August 2016 underwent sleep studies to assess for evidence of sleep-disordered breathing. Data was collected on their demographics as well as lung health, medication burden and levels of atopic disease. Separately, children with proven OSA undergoing adenotonsillectomy as a treatment option were recruited and their level of atopy assessed using clinical questionnaire and evidence of peripheral blood sensitisation. Children undergoing surgery for recurrent tonsillitis were recruited as a disease control and underwent the same process. The extracted tonsil tissue was analysed to explore cellular phenotype between those with confirmed OSA and those without. The T-cells were one area of interest along with innate lymphoid cells (ILCs), a recently described novel class of leukocytes assigned critical roles in asthma pathology. Amongst the STRA group 21 children underwent a sleep study with 3 (14%) demonstrating evidence of OSA. No difference could be identified based on their demographics, medical therapy, respiratory health or level of atopy. For the children undergoing tonsillectomy, 24 with OSA and 21 disease control subjects were recruited. The rate of peripheral sensitisation was higher in the Non-OSA group (OSA group 5 (20%) vs Non-OSA group 10 (48%), P=0.11). From the extracted tissue, a lower proportion of T-regulatory cells (Tregs) (CD4+CD25+Foxp3+) was observed in the tonsils of children with OSA compared to controls as both cell counts per gram of tissue and percentage of total cells. A similar result was seen on the peripheral blood of these subjects. Regarding the innate lymphoid cells (ILCs) no difference was observed between OSA and Non-OSA subjects. A higher proportion however was observed in tonsil tissue amongst those with proven atopy compared to the non-atopic subjects. The incidence of OSA within the STRA subjects was not found to be higher than the background incidence in children and less severe than previously published. For the subjects recruited from those listed for tonsillectomy, no difference in atopic status was observed from questionnaire data or laboratory analysis suggesting this was not impacting the development of OSA however this was a small study population affecting any conclusion drawn. The tonsil and peripheral blood of children with OSA had significantly fewer Tregs compared to controls. This finding has not been reported previously in tonsil tissue with a control group analysis and supports similar findings from adenoidal tissue and peripheral blood implicating Tregs in the underlying pathology. The higher proportion of tonsil ILCs in subjects with atopic disease is also a significant finding and supports the notion of the innate immune systems role in atopic disease. In conclusion, I observed no difference in the incidence of OSA amongst STRA children compared to the incidence in childhood or atopy amongst children with confirmed OSA compare to those without OSA. I did however identify lower Treg cells in the tonsil and peripheral blood of children with OSA compared to disease control subjects and an association between ILCs and atopy.