Responses to Surgical and Bronchoscopic Volume Reduction

描述(由申请人提供)：肺减容手术是一种 治疗终末期肺气肿的有效辅助药物。临床 结果表明，LVRS的工作原理是消除严重疾病和 肺功能失调。我们之前曾假设有效的减量 有可能使用非手术方法导致永久性肺不张 特定的目标区域。通过折叠这些区域并应用 基于纤维蛋白的密封剂，我们已经证明有可能达到肺容量 不做手术的绵羊肺气肿模型的复位术。虽然这些研究 证实了我们最初的假设，他们还证明了几个重要的 缺点。完全通过机械坍塌实现的BVR和应用 纤维蛋白密封剂经常是不完整的。只有1/2到1/3的目标区域 随访2个月时仍萎靡不振。此外，几个目标区域 出现组织坏死。为了解决这些限制，我们修改了我们的 接近BVR。新一代试剂已经开发出来，它可以 调节局部细胞反应，促进成纤维细胞生长和瘢痕形成 形成而无坏死。初步研究表明，这些 修改解决了我们最初研究中确定的限制。我们现在 假设：使用洗涤液+胶水可以改善BVR 导致部位特异性塌陷的试剂，并调节成纤维细胞和 上皮细胞生物学，以产生受控、高效的疤痕形成。这个 这项建议的目标是：1)表征生理和 利用这些改良试剂对绵羊的生物反应 肺气肿，以及2)将结果与传统手术结果进行比较 心理治疗。我们相信，通过实现这些目标，我们可以帮助推进 这项技术进入了临床领域。

DESCRIPTION (provided by applicant): Lung volume reduction surgery (LVRS) is an effective adjunct to medical treatment for end stage emphysema. Clinical results suggest that LVRS works by eliminating areas of severely diseased and dysfunctional lung. We previously hypothesized that effective volume reduction might be possible using a non-surgical approach to cause permanent atelectasis of specific target regions. By collapsing these regions and applying a fibrin-based sealant, we have shown that it is possible to achieve lung volume reduction without surgery in a sheep model of emphysema. While these studies confirmed our initial hypothesis, they have also demonstrated several important shortcomings. BVR achieved solely by mechanical collapse and application of fibrin sealant is frequently incomplete. Only 1/2 to 1/3 of the target regions remained collapsed at 2month follow-up. Furthermore, several target regions developed tissue necrosis. To address these limitations, we have modified our approach to BVR. A new generation of reagents has been developed which modulates local cellular responses, and promotes fibroblast in-growth and scar formation without necrosis. Preliminary studies indicate that these modifications address the limitations identified in our original study. We now hypothesize that: improved BVR can be achieved using washout solution + glue reagents which cause site-specific collapse, and modulation of fibroblast and epithelial cell biology to generate controlled, efficient scar formation. The objectives of this proposal are to: 1) characterize physiological and biological responses using these improved reagents in a sheep model of emphysema, and 2) compare results to those obtained using conventional surgical therapy. We believe that by accomplishing these objectives, we can help advance this technology into the clinical arena.