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Apoptosis is a physiological process essential for homeostasis of epithelial organisation and function. CF lung disease is characterised by chronic infection and inflammation and previous work suggests that apoptosis is dysfunctional in the CF airways with conflicting results. In addition, controversy exists regarding how CFTR misfolding contributes to apoptosis. In this study, we evaluated the relationship between CFTR mutation and apoptosis in DF508-CFTR CF airway epithelial cells. Basal activity of the executioner caspase, caspase-3, was significantly increased in CF tracheal and bronchial epithelial cell lines and primary bronchial epithelial cells compared to non-CF controls. In addition, activity of the upstream initiator caspase, caspase-8, was significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells, and neutralization of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. Furthermore, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway.

Introduction: Cystic fibrosis related diabetes (CFRD) is increasing. We aim to determine HbA1C ranges and incidence of complications in CFRD pts when age/sex matched to non-CF diabetic controls. Methods: 11 CFRD patients (mean age 23.5 SE 1.49, 7M/4F) were age/sex matched to non-CF, type I diabetics (mean age 23.6 SE 1.52, 7M/4F). The HbA1C range (over 3 y), length from dx and all complications of DM recorded. Results: CFRD had comparable ranges of HbA1C than age/sex matched controls (range 4.8 15.1%, mean 7.90% SE 0.41, and 5.0 14.6%, mean 8.73% SE 0.41, respectively) [p-value 0.05]. Duration of DM differed b/w the gps; CFRD (mean 3.56 yrs/median 3 yrs) and non-CF diabetics (mean 9.61 yrs/median 8 yrs) [p-value