Background: Lung cancer is the most common cause of cancer related death in Ireland. The majority of lung cancers are inoperable at the time of diagnosis and consequently the overall 5 year survival is less than 10%. The objective of the ProActive Lung Cancer Detection (PALCAD) study was to evaluate whether low dose chest computed tomographic scanning (LDCCT) can detect early stage asymptomatic lung cancer in a high risk urban population. Methods: Four hundred and forty nine subjects of median age 55 years (range 50-74) with a median pack year smoking history of 45 years (range 10-160), with no previous cancer history and medically fit to undergo thoracic surgery were recruited. After informed consent, LDCCT was performed on all subjects. Non-calcified nodules (NCNs) of >10 mm in diameter were referred for biopsy. Follow up with interval LDCCT at 6, 12 and 24 months to exclude growth was recommended for NCNs ,10 mm in diameter. Results: Six (1.3%) NCNs of >10 mm were detected of which one (0.23%) had non-small cell lung cancer stage 1; 145 NCNs of ,10 mm were detected in 87 (19.4%) subjects. Mediastinal masses were detected in three subjects (0.7%)-one small cell lung cancer and two benign duplication cysts. Incidental pathology was noted in 276 patients (61.5%), most commonly emphysema and coronary artery calcification. Conclusion: The prevalence of resectable lung cancer detected by LDCCT at baseline screening was low at 0.23%, but there was a high rate of significant incidental pathology.

Limited echocardiography-guided management following early resuscitation is associated with improved survival, less fluid, and increased inotropic prescription. A prospective randomized control trial is required to verify these results.

The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium. Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations. We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged. Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression. We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease. Using an airway epithelial cell line, we found a dosedependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts. Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein. The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS. Stimulation with salmeterol (10 -6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect. The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression. Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens.