N.G. McElvaney

Diagnosis and Management of Asthma in Older Adults

Despite comprehensive guidelines established by the European Global Initiative for Asthma and the U.S. National Asthma Education and Prevention Program on the diagnosis and management of asthma, its mortality in older adults continues to rise. Diagnostic and therapeutic problems contribute to older patients being inadequately treated. The diagnosis of asthma rests on the history and characteristic pulmonary function testing (PFT) with the demonstration of reversible airway obstruction, but there are unique problems in performing this test in older patients and in its interpretation. This review aims to address the difficulties in performing and interpreting PFT in older patients because of the effects of age‐related changes in lung function on respiratory physiology. The concept of “airway remodeling” resulting in “fixed obstructive” PFT and the relevance of atopy in older people with asthma are assessed. There are certain therapeutic issues unique to older patients with asthma, including the increased probability of adverse effects in the setting of multiple comorbidities and issues surrounding effective drug delivery. The use of beta 2‐agonist, anticholinergic, corticosteroid, and anti‐immunoglobulin E treatments are discussed in the context of these therapeutic issues.

WS9.2 Abnormal lipid raft structure as a potential cause for impaired neutrophil activity in cystic fibrosis

WS9.1 Clinical isolates of Prevotella histicola drive MMP-9 secretion by mononuclear cells M.V. Jackson1, C.M. O’Kane2, M. Tunney3, J.S. Elborn4. 1Queen’s University Belfast, School of Pharmacy, Belfast, United Kingdom; 2CF & Airways Microbiology Research Group, Queen’s University, Centre for Infection and Immunity, Belfast, United Kingdom; 3CF & Airways Microbiology Research Group, Queen’s University, School of Pharmacy, Belfast, United Kingdom; 4CF & Airways Microbiology Research Group, Queen’s University, Centre for Infection and Immunity, Belfast, United Kingdom

147 Comparative analysis of inflammatory markers in cystic fibrosis and non-cystic fibrosis bronchiectasis

Objetives: Oxidative stress is believed to play an important role in the pathophysiology of cystic fibrosis (CF). Many factors may contribute to increased oxidative stress in CF, as the disease combines the increased production of reactive oxygen species (ROS) with impaired antioxidant protection. The aim, therefore, of this study was to evaluate oxidative stress using different biomarkers (both plasma and intracellular in peripheral blood leukocytes) in a group of clinically stable adult patients with bronchiectasis (CF and non-CF) and compare the results with a group of healthy controls. Methods: This cross-sectional study included 90 patients with a diagnosis of bronchiectasis with and without CF, periodically monitored in the adult bronchiectasis/CF unit at a university hospital. A control group comprised 50 healthy subjects, matched with respect to patient sex, age and nutritional status. The intracellular oxidative stress biomarkers (mitochondrial membrane potential, superoxide anion and hydrogen peroxide and intracellular glutathione) were analyzed in white blood cells as total leukocytes, neutrophils, lymphocytes and monocytes. The plasma oxidative stress biomarkers (total antioxidant capacity, glutathione peroxidase activity, superoxide dismutase activity, catalase activity, 8-iso-prostaglandin F2a, TBARs) were measured. Conclusions: Cell and plasma markers of oxidative stress were raised in the patients with bronchiectasis as compared with the controls and no differences depending on the cause of the bronchiectasis (CF vs non-CF) were found.

152 Estrogen-regulated MicroRNAs control the expression of secretory leukoprotease inhibitor in monocytes

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.

151 Investigation of MicroRNA regulation of interleukin-8 production in bronchial epithelial cells

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.

265 Complications of diabetes in an adolescent Cystic Fibrosis population

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 <0.05]. Both groups experienced hypoand hyperglycemia. Only the control group (n 2, 18.1%) experienced microvascular complications. Neither group had macrovascular complications. DKAs were isolated to the control group; 45.0% (n 5). One CFRD had steroid induced diabetes, and one control patient developed autoimmune hypothyroidism. Other complications included recurrent urinary tract (n 3) and fungal nail infections (n 1). Conclusions: CFRD are similarly controlled compared to age/sex matched counterparts reflected by HbA1C levels. Poorer nutritional status in CF can explain differing mean HbA1C levels. Absence of microvascular complications in CFRD reflects later onset/shorter duration of DM. Both groups receive insulin, and the absence of DKAs among CFRD suggests presence of residual endogenous insulin secretion. Although HbA1C is regularly used to monitor glycaemic control in both groups, it must not be used for diabetic screening. A formal OGTT carried out regularly (yearly after age 10) is the gold standard for a diagnosis of DM in all CF patients. 7. Metabolic complications of CF