Management of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is a prevalent condition in the UK, associated with high morbidity and mortality. Hospital physicians manage a significant portion of acute chronic obstructive pulmonary disease admissions to hospital and readmissions after discharge. Optimal management of exacerbations requires controlled oxygen therapy and ventilatory support where necessary, and careful administration of bronchodilators, steroids and antibiotics. Holistic care for these patients includes nutritional supplementation and palliative support for those with advanced disease. To reduce the chance of readmission, chronic obstructive pulmonary disease care bundles can be used, along with a review of inhaled and oral therapies. Where available, hospital-at-home discharge schemes can safely facilitate early discharge. Most importantly, high quality evidence-based smoking cessation support must be offered to smokers. Exercise improves the physiological and psychological condition of people with chronic obstructive pulmonary disease and should be encouraged, with referral to a pulmonary rehabilitation service if available.

Endothelin-1 stimulates small artery VCAM-1 expression through p38MAPK-dependent neutral sphingomyelinase.

Endothelin-1 (ET-1) stimulates vascular cell adhesion molecule (VCAM-1) expression, a process associated with arterial remodelling. However, the pathways activated by ET-1 that lead to VCAM-1 expression are not fully understood. It is reported that sphingomyelinases are necessary for VCAM-1 expression in response to cytokines. Our aim was to investigate the role of sphingomyelinases in ET-1-induced VCAM-1 expression. Acid and neutral sphingomyelinase activities were measured in extracts from rat mesenteric small arteries (RMSA). ET-1 (1-100 nmol/l) stimulated neutral but not acid sphingomyelinase. The activation was rapid, peaking within 5 min and transient, returning towards baseline by 10 min and inhibited by BQ-788, GW4869 and SB203580, which are inhibitors of ET(B) receptor, neutral sphingomyelinase and p38MAPK, respectively. Both GW4869 and SB203580 are reported to inhibit activation of neutral sphingomyelinase 2 implicating it in the response to ET-1. Accordingly we investigated the expression of this isoform and found it was present in RMSA, predominantly in endothelial cells. Treatment of RMSA with ET-1 (1-100 nmol/l) for 16 h increased VCAM-1 expression, which was inhibited by GW4869 and SB203580. These results indicate that ET-1 stimulates arterial VCAM-1 expression through p38MAPK-dependent activation of neutral sphingomyelinases. This suggests a role for sphingolipids in ET-1-induced vascular inflammation in cardiovascular disease.