Abstract
Northern Territory Indigenous children experience a high burden of chronic suppurative lung disease (CSLD) associated with recurrent lower respiratory infection. There are currently limited data to guide effective long-term management strategies for CSLD.This thesis investigates the role of the immune response, particularly in relation to non-typeable Haemophilus influenzae (NTHi), in the pathogenesis of chronic suppurative lung disease in Northern Territory children. The findings from this thesis provide biological evidence in support of novel management strategies to improve the clinical outcome for Northern Territory children with CSLD.
Principal findings:
1. A prospective evaluation study showed that flexible bronchoscopy with lavage substantially contributes to the clinical management of children with CSLD by identifying airway eosinophilia and respiratory pathogens not addressed by current empiric therapies.
2. In vitro studies of innate, and adaptive immune responses to NTHi showed that:
a. Children with CSLD generate a functionally distinct cell-mediated immune phenotype in response to NTHi compared with respiratory-healthy children.
b. The NTHi-driven cytokine profile in children with CSLD is associated with mechanisms regulating inflammation in the lungs.
3. A study of children vaccinated with a Pneumococcal H. influenzae Protein D conjugate vaccine provided proof-of-concept that the functional immune profile can be modified in children with CSLD.
The findings from this thesis contribute to the development of novel management strategies for CSLD in Northern Territory children by identifying factors of the immune response, likely contributing to the pathogenesis of CSLD, that may be targeted by novel therapeutic interventions. These data lay the foundation for studies to evaluate the effect of novel interventions on the clinical outcomes of Northern Territory children with CSLD.
Note: Please note that some articles in the thesis is available in hard copy only.
| Date of Award | Feb 2015 |
|---|---|
| Original language | English |
| Supervisor | Anne Chang (Supervisor) |