Current Opinion in Pharmacology

Front-runners for pharmacotherapeutic correction of the airway ion transport defect in cystic fibrosis.

Publication Date: 2008 May 7 PMID: 18468487
Authors: Clunes, M. T. - Boucher, R. C.
Journal: Curr Opin Pharmacol

Although cystic fibrosis (CF) patients display multiorgan dysfunction (e.g. pancreas, gut, and lung) it is lung disease that is the leading cause of premature death in these patients. CF lung disease is characterized by persistent pulmonary infection and mucus plugging of the airways initiated by the failure of solute transport across the airway epithelium. Many drug therapies aim to alleviate the secondary characteristics of CF lung disease; however, new therapies in development are targeted at correcting the ion transport deficiency of CF. The goal is to hydrate airway surfaces by stimulating secretion (through activation of the CF transmembrane conductance regulator and calcium-activated chloride channels), and/or inhibiting absorption (through the epithelial sodium channel) thereby stimulating healthy mucociliary clearance. If mucociliary clearance can be stimulated sufficiently from an early age, then there is the possibility that secondary lung infection may be eradicated from the syndrome of CF disease.

post to: CiteULike

Vascular endothelial growth factor of the lung: friend or foe.

Publication Date: 2008 May 7 PMID: 18468486
Authors: Tuder, R. M. - Yun, J. H.
Journal: Curr Opin Pharmacol

The discovery of vascular endothelial growth factor (VEGF) changed the field of angiogenesis. We have learned that VEGF has broader actions than merely a driver of tumor angiogenesis, particularly that VEGF controlled several fundamental functions and properties of endothelial cells and nonendothelial cells. The lung is one of the main organs where VEGF controls several crucial physiological functions. These actions rely on tightly regulated temporal and concentration gradients of VEGF and VEGF receptor expression in the lung. Excessive or diminished VEGF have been linked to abnormal lung phenotypes and, in humans, linked to several diseases. The beneficial and detrimental actions of VEGF underscore that therapeutic targeting of VEGF in disease has to carefully consider the lung biology of VEGF.

post to: CiteULike

The clinical utility of biomarkers in asthma and COPD.

Publication Date: 2008 May 7 PMID: 18468485
Authors: Snell, N. - Newbold, P.
Journal: Curr Opin Pharmacol

Biomarkers with potential utility in the diagnosis and prognosis of asthma and chronic obstructive pulmonary disease (COPD), and in monitoring the natural history of these diseases and the effect of therapeutic interventions, are being widely researched. This review critically describes the methodologies used for obtaining and analysing appropriate biofluid, tissue and exhaled breath samples for biomarker analysis. Currently measurements of sputum eosinophils and exhaled nitric oxide in asthmatics are the best established markers for disease activity and response to anti-inflammatory therapy. Circulating C-reactive protein (CRP) levels have been shown to predict risk of hospitalisation and death from COPD. Biomarker measurements in exhaled breath condensate are the least well-validated techniques. Other assessments in both conditions have potential value in clinical use but require further research and validation.

post to: CiteULike

Frontrunners in novel pharmacotherapy of COPD.

Publication Date: 2008 May 3 PMID: 18457992
Authors: Barnes, P. J.
Journal: Curr Opin Pharmacol

The mainstay of current drug therapy is long-acting bronchodilators; several longer acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. No treatments reduce the progression or suppress the inflammation of COPD. With better understanding of the inflammatory and destructive process, several new targets have been identified. Several mediator antagonists tested in COPD have been disappointing, but of CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment may be more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of PDE4, p38 MAPK and NF-kappaB, but side effects will be a major limitation so that inhaled delivery will be necessary. Perhaps the most promising approach is reversal corticosteroid resistance through increasing HDAC2 activity. This may be achieved by theophylline-like drugs, more effective antioxidants and non-antibiotic macrolides.

post to: CiteULike

Thymic stromal lymphopoietin: a new cytokine in asthma.

Publication Date: 2008 Apr 29 PMID: 18450510
Authors: Rochman, Y. - Leonard, W. J.
Journal: Curr Opin Pharmacol

Airway epithelial cells provide mechanical and immune protection against pathogens and allergens. Following activation, these cells produce a wide range of cytokines including thymic stromal lymphopoietin (TSLP). Recently it was established that a high level of TSLP is associated with asthma in mice and in humans. These findings suggest that interfering with the ability of cells to respond to TSLP might prevent the development of airway inflammation. Our review presents current knowledge on mediators that induce TSLP production and on the actions of TSLP on different populations of cells that are related to airway inflammation. TSLP affects dendritic cells, T cells, NKT cells, and mast cells, indicative of the broad role of TSLP in the regulation of inflammatory/allergic processes.

post to: CiteULike