LUNG VOLUME REDUCTION USING A BRONCHOSCOPIC APPROACH

减容手术(VRS)最近被成功地应用于终末期慢性阻塞性肺疾病(COPD)的治疗。VRS后肺功能的改善被认为与切除肺气肿组织直接相关，到目前为止，这是通过几种不同但同样成功的手术方法实现的。与所采用的技术无关，VRS的治疗目标是相同的：消除肺组织病变和功能障碍的靶区，并总体减少肺过度扩张，目的是改善弹性后坐、呼吸道捆绑和呼吸肌功能。鉴于这一目标，我们假设可以通过支气管镜下实现有效的、可控的和临床安全的体积减少，这种方法可以在不需要肺组织切片的情况下减少选定靶区的体积。这一假说的基本原理是基于对决定肺泡稳定性的表面张力和组织反弹力的考虑，以及如何改变这些因素之间的平衡。通过使用能够改变这种力平衡的生物兼容溶液，使用支气管镜将其安装到选定的靶区，应该可以使用支气管镜产生定向的、持续的肺泡塌陷到选定的靶区，应该可以产生定向的、持续的肺泡塌陷，从而有效地实现肺体积减少。初步研究表明，将需要3个步骤。最初的干预措施包括注入生物相容的溶液(“抗表面活性物质”)，这些溶液会增加小气道和肺泡的气液界面的表面张力，导致力不平衡和坍塌。目前正在考虑两种策略，以确保可以有效地消除目标区域内的任何气体，以允许接近相邻的肺泡面。这些干预是通过特定的操作来促进成纤维细胞的生长和永久疤痕形成的。最终的结果应该是持续的容量减少，在功能上等同于手术可以达到的效果。如果这一假设是正确的，这里提出的方法有可能降低与减容手术相关的发病率和死亡率，并使终末期肺部疾病患者可以使用该程序，否则他们可能因为存在显著的并存疾病而不符合手术条件。这项建议的目的是验证这一假设，并将支气管镜体积缩小到可以考虑用于人体试验的程度。

Volume reduction surgery (VRS) has recently been successfully employed for the treatment of end stage chronic obstructive pulmonary disease (COPD). Improvement in lung function following VRS is thought to be directly related to resection of emphysematous lung tissue which, to date, has been accomplished using several distinct, but equally successful, surgical approaches. Independent of the technique employed, the therapeutic objectives of the VRS are the same: to eliminate target regions with diseased and dysfunctional lung tissue, and to produce overall reduction in lung hyper-expansion with the objective of improving elastic recoil, airway tethering, and respiratory muscle function. Given this objective, we hypothesize that effective, controlled, and clinically safe volume reduction can be achieved bronchoscopically using a non-surgical approach which can reduce the volume of selected target regions without requiring section of lung tissue. The rationale for this hypothesis is based on a consideration of the surface tension and tissue recoil forces which dictate alveolar stability, and how the balance between these factors can be altered. By using biocompatible solutions capable of altering this force balance which are installed into selected target regions using a bronchoscope, it should be possible to generate directed, sustained alveolar collapse into selected target regions using a bronchoscope, it should be possible to generate directed, sustained alveolar collapse, and thus, in effect, achieve lung volume reduction. Preliminary studies suggest that 3 steps will be required. The initial intervention involves instillation of biocompatible solutions ("anti-surfactants") which increase surface tension at the air-liquid interface of small airways and alveoli, resulting in force imbalance and collapse. Two strategies are being considered to ensure that any gas trapped within the target region can be effectively eliminated to allow for approximation of adjacent alveolar surfaces. These interventions are accomplished by specific maneuvers to promote fibroblast in growth and permanent scarring. The final result should be sustained volume reduction, functionally equivalent to that which can be achieved surgically. If this hypothesis is correct, the methodology proposed here has the potential for reducing morbidity and mortality associated with volume reduction surgery, and for making the procedure available to patients with end stage lung disease who might not otherwise be eligible for surgery because of the presence of significant co-morbidity. The objective of this proposal is to test this hypothesis, and develop bronchoscopic volume reduction to such an extent that it could be considered for human trials.