- To determine the glycosylation of specific salivary proteins in CF and health, and correlate changes, to level of infection and severity of lung disease.
- To determine the levels of Pseudomonas elastase in sputum and measure serum anti-Pseudomonas Ig G2 and Ig A1 and salivary secretory Ig A (slg A) and assess their correlation to lung destruction.
- To assess glycoproteins in affected tissues of a CF mouse-model using lectin - biochemistry, histochemistry and immunocytochemistry.
The biochemical defect in cystic fibrosis (CF) is related to dysfunction of a chloride channel which causes increased tonicity of salt in exocrine secretions and changes in secretory protein glycosylation. Most of the CF afflicted individuals suffer from recurrent pulmonary infections by opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa and these infections accompanied by the individual's immune reaction lead to destruction of the lung. However, a small percentage of CF patients show mild pulmonary disease and this appears to be related to the presence of a residual chloride conductance in afflicted tissues. Since current evidence suggests that increased sialylation, fucosylation and sulphatin of mucous glycoproteins in the oral cavity and in tracheal secretions is pivotal to the colonization of the lungs, it can by hypothesised that the retention of a chloride conductance in tissues showing a mild phenotype could be manifest in the normalization of protein glycosylation. Lung disease in cystic fibrosis is therefore multi-factorial, and it is important to assess the relationships between each of these factors in the disease process. This Concerted Action on lung disease in CF with its clinical support will evaluate a common set of samples by drawing upon the expertise of partners specialising in various aspects of CF research. By fulfilling its objectives the project should establish factors correlated with severe lung disease or factors correlated with mild lung disease and by doing so should give indications of possible therapeutic approaches. Data from the various studies will be centrally collated and a bank of CF samples created. At the end of the project recommendations will be made on the most efficient use of current therapies in CF, and areas of future drug development aimed at the prevention of lung disease identified.