Effect of Losartan on Progression of Emphysema

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is a major cause of death and disability in the United States. Current treatments target bronchospasm and inflammation of airways with the goal to reduce symptoms and prevent exacerbations. However, other than smoking cessation, no treatment has been found that modifies the progression of this disease. Moreover, COPD is a heterogeneous disease involving remodeling of both lung parenchyma (emphysema) and airways (chronic bronchitis). Research in mice exposed to cigarette smoke implicates TGF-beta signaling as a mediator of apoptosis that leads to emphysema. The development of emphysema can be prevented by blockade of the angiotensin-1 (AT1) receptor with drugs such as losartan. A pilot study of losartan in patients with COPD showed no overall improvement, but patients who had the emphysema phenotype demonstrated no progression of emphysema at 1 year compared to placebo treated patients who increased the percent of lung occupied by emphysema. These results did not reach statistical significance (p = 0.06) but were strongly suggestive of a benefit in COPD patients with emphysema. The aim of this proposal is to conduct a definitive randomized, placebo-controlled, clinical trial to test whether administration of 100mg/day of losartan to patients with radiographic evidence of emphysema will slow progression of their disease compared to comparable individuals given placebo. Emphysema progression will be measured by high-resolution computed tomography using standardized procedures. The trial is designed to be a highly-focused pragmatic trial with sparse data collection that can be accomplished in community as well as academic settings.