Background: The ciliated respiratory epithelium that covers the surface of human airway forms an immunologically active natural barrier to invasion and injury by inhaled noxious agents. Ciliary dysfunction and or epithelial damage compromise this innate defence mechanism. Aim: To study the ciliary function and epithelial ultrastructure of adult patients with asthma and paediatric lung transplant recipients. To study the response of bronchial epithelial cells of patients with atopic severe asthma, to allergen and bacteria. Methods: Digital high speed video microscopy was used to study the ciliary function on bronchoscopic bronchial epithelial brushings. Transmission electron microscopy was used to study the detailed epithelial ultrastructure. Cytokines and chemokines released by primary bronchial epithelial cells were measured using SECTOR Imager 6000 (MSD, USA). Results: Ciliary dysfunction and ultrastructural abnormalities are closely related to asthma severity. Ciliary dysfunction is a feature of moderate to severe asthma and profound ultrastructural abnormalities are restricted to severe disease. Primary bronchial epithelial cells of patients with atopic severe asthma and healthy controls are capable of releasing chemokines and cytokines in response to Dermatophagoides Pteronyssinus allergen 1 and Streptococcus pneumoniae in a dose and time dependent manner. Ciliary dysfunction is a feature of native airway epithelium in paediatric Cystic Fibrosis lung transplant recipients. The allograft epithelium shows profound ultrastructural abnormalities in both Cystic Fibrosis and non-suppurative lung disease lung transplant recipients. Summary: The phenotype of secondary ciliary dyskinesia and the differential cytokine/chemokine response of the epithelium of patients with severe asthma seen in this study extend our current paradigm of severe asthma and present a new therapeutic target. The damaged allograft epithelium seen in paediatric lung transplant recipients may increase risk of microbial colonisation of the allograft airway, which may play a role in the development of Bronchiolitis Obliterans Syndrome (BOS).
|Publisher||University of Leicester|
|Source Sets||Ethos UK|
|Type||Electronic Thesis or Dissertation|
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