Introduction of a comprehensive management protocol for severe sepsis is associated with sustained improvements in timeliness of care and survival.

INTRODUCTION: Mortality from severe sepsis can be improved by timely diagnosis and treatment. This study investigates the effectiveness of a comprehensive management protocol for recognition and initial treatment of severe sepsis that spans from the emergency department (ED) to the intensive care unit. METHODS: Interventions included development of a management algorithm including early goal-directed therapy, a computerised physician order entry set for suspected sepsis, introduction of invasive haemodynamic monitoring and antibiotics stocked in the ED, and an extensive education campaign involving ED nurses and physicians. MAIN RESULTS: In the 6 months after introduction of the protocol, 37 patients who had severe sepsis were identified in the ED. Compared to a randomly selected group of 37 patients who had severe sepsis and who were transferred directly to the intensive care unit before introduction of the protocol, significant improvements were observed in mean time to initiation of early goal-directed therapy (3.2 vs 10.4h, p=0.001) and to achievement of resuscitation goals (10.4 vs 30.1h, p=0.007). There was a trend towards more rapid administration of antibiotics (1.4 vs 2.7h, p=0.06). This was associated with a decrease in crude hospital mortality rate from 51.4% to 27.0% (absolute risk reduction=24%, 95% CI 3% to 47%). Improvements were sustained in the follow-up audit at 16 months. CONCLUSIONS: Introduction of a comprehensive management protocol to address early recognition and management of severe sepsis in the ED is associated with sustained improvements in processes of care.

Conjugated linoleic acid improves airway hyper-reactivity in overweight mild asthmatics.

BACKGROUND: Conjugated linoleic acids (CLA) are naturally occurring fatty acids that have multiple biological properties including the regulation of metabolic, proliferative and immune processes. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of CLA as a dietary supplement in mild asthma. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Twenty-eight adult subjects (aged 19-40 years) with mild asthma (FEV(1)>70% predicted) were randomized to CLA 4.5 g/day or placebo for 12 weeks in addition to usual treatment. On average, subjects were overweight with a mean body mass index (BMI) of 27.9 kg/m(2). RESULTS: Subjects in the CLA group had a significant improvement in airway hyperresponsiveness (AHR) at week 12 compared with week 0 [PC(20) 6.6 (2.1) mg/mL vs. 2.2 (0.7) mg/mL; P<0.05]. The CLA group had a significant reduction in weight and BMI compared with placebo and this was associated with a reduction in leptin/adiponectin ratio. There were no differences in systemic cytokine levels, induced sputum cell counts, quality-of-life scores or adverse events. CONCLUSIONS: CLA treatment as an adjunct to usual care in overweight mild asthmatics was well tolerated and was associated with improvements in AHR and BMI.

Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury.

Fas-mediated apoptosis of the alveolar epithelium is important in the pathogenesis of acute respiratory distress syndrome. Erythropoietin (EPO) has cytoprotective properties in other organ systems, and is relatively deficient in critical illness. This study investigates a potential role for EPO in reducing apoptosis in a model of acute lung injury. Apoptosis was induced in human alveolar epithelial (A549) cells or normal human bronchial epithelial (NHBE) cells by Fas activation with CH-11 Fas-crosslinking antibody or by co-culture with polymorphonuclear neutrophils in a transwell system. The effect of recombinant human (rh)EPO on apoptosis was measured by poly(ADP-ribose) polymerase cleavage and cell death detection assay. The specific EPO-EPO receptor (EPOR)-mediated effect was determined using an EPO-blocking antibody or EPOR small interfering RNA. Expression of EPOR was demonstrated in A549, NHBE and normal human alveolar epithelium. Fas- and neutrophil-mediated apoptosis of A549 and NHBE cells was inhibited by rhEPO by a specific EPO-EPOR-mediated mechanism. This anti-apoptotic effect was associated with induction of a pro-apoptotic Bcl-xL/Bax ratio. EPO has cytoprotective properties in respiratory epithelium in an in vitro model, which may indicate a potential therapeutic role in acute lung injury.

Screening for lung cancer using low dose CT scanning: results of 2 year follow up.

BACKGROUND: Screening with low dose chest computed tomographic scanning (LDCCT) may improve survival by identifying early asymptomatic lung cancer. METHODS: Four hundred and forty nine high risk subjects were screened with serial LDCCT scanning over 2 years. Fine needle aspiration biopsy was recommended for non-calcified nodules (NCNs) of >10 mm diameter or demonstrating interval growth. RESULTS: NCNs were identified in 111 subjects (24.7%), three of which were lung cancer. The overall prevalence (0.4%) and incidence (1.3%) rates of lung cancer detection were low. Three of the six lung cancers detected in the study were stage 1 non-small cell lung cancer; the remainder were unresectable central tumours. By contrast, eight subjects developed extrathoracic malignancy during the study period and other incidental pathology was noted in 221 subjects (49.2%). Smoking cessation rates at 19% were higher than in the general population, but 60.8% of subjects continued to smoke. CONCLUSION: LDCCT scanning is useful in detecting early peripheral non-small cell lung cancers but its usefulness as a screening tool is limited by low specificity and by poor sensitivity for central tumours.

Screening for lung cancer using low dose CT scanning.

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.

Treatment of persistent dry cough: if possible, treat the cause; if not, treat the cough.

Persistent dry cough is a common presenting symptom which may be associated with considerable morbidity. In the majority of patients, systematic investigation reveals an underlying cause, usually asthma, postnasal drip, gastrooesophageal reflux or various combinations of these conditions. Intensive treatment of the underlying cause usually leads to improvement or resolution of the cough. However, in a minority of patients, no underlying cause is identified despite appropriate investigation. In these patients with idiopathic persistent dry cough, cough sensitivity to inhaled tussigens is enhanced, suggesting that increased sensitivity of airway sensory nerves is important in pathogenesis. An ideal antitussive would reduce this increased sensitivity to normal levels without significant adverse effects but currently available antitussives fall short of this expectation. This review discusses the currently available antitussive therapy and explores potential avenues for the development of future novel antitussive therapies.