Nasal AEC cultures were established from children (0.6-14.9 years) undergoing elective surgical procedures under general anaesthetic, categorised as atopic asthmatics (n=12), virus-induced wheezers (n=8) or healthy controls (n=32) using questionnaire and serum IgE levels. All subjects were free of current respiratory symptoms. Successful AEC cultures were maintained to passage 2 or 41 (79%) subjects. AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. When the wheezing phenotypes were considered separately, AEC from atopic asthmatic children released significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from controls but there were no significant differences between AEC mediator release from children with virus-induced wheeze and either atopic asthmatics or controls. Similar results were found for cytokine-stimulated AEC. In non-wheezy subjects, there were no differences in AEC mediator release between atopic and non-atopic individuals. There were no differences between the study groups in the percentage increments in mediator release in response to stimulation. In multivariate analysis, taking into account age, gender, passive smoke exposure, use of inhaled corticosteroids, total serum IgE and specific responses to inhaled aeroallergens as possible confounders, wheeze was the only significant predictor of AEC mediator release. It was concluded that there are intrinsic differences in AEC from children with a history of wheeze compared to healthy controls and these are independent of atopic status. This study provides further evidence that the airway epithelium is implicated in the pathogenesis of childhood wheezing. It is hypothesised that different systemic factors, such as atopy and viral responsiveness, interact with common epithelial abnormalities to give rise to different wheezing phenotypes. Further work is required to establish whether these abnormalities are primary or secondary and to confirm these findings in well-differentiated AEC cultured with an air-liquid interface.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499633 |
| Date | January 2008 |
| Creators | McDougall, Catherine M. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25500 |
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