LUNG VOLUME REDUCTION USING A BRONCHOSCOPIC APPROACH

肺减容手术（VRS）最近已成功地用于治疗终末期慢性阻塞性肺疾病（COPD）。VRS后肺功能的改善被认为与肺气肿肺组织的切除直接相关，迄今为止，已经使用几种不同但同样成功的手术方法完成了肺气肿肺组织的切除。与所采用的技术无关，VRS的治疗目的是相同的：消除具有患病和功能障碍的肺组织的靶区域，并产生肺过度扩张的总体减少，目的是改善弹性回缩、气道束缚和呼吸肌功能。鉴于这一目的，我们假设可以使用非手术方法在支气管镜下实现有效、受控和临床安全的减容，该方法可以减少选定靶区域的体积，而无需切除肺组织。这一假设的基本原理是基于对表面张力和组织反冲力的考虑，这些因素决定了牙槽骨的稳定性，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相容性解决方案，其使用支气管镜安装到选定的目标区域中，应该可以使用支气管镜在选定的目标区域中产生定向的、持续的肺泡萎陷。应该可以产生定向的、持续的肺泡萎陷，并且因此实际上实现肺体积减小。初步研究表明，需要采取三个步骤。最初的干预包括滴注生物相容性溶液（“抗表面活性剂”），其增加小气道和肺泡的气液界面处的表面张力，导致力不平衡和塌陷。正在考虑两种策略，以确保任何气体被困在目标区域内可以有效地消除，以允许相邻肺泡表面的近似。这些干预措施是通过特定的操作来促进成纤维细胞生长和永久性瘢痕形成。最终的结果应该是持续的减容，功能上等同于手术可以实现的减容。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，并使该手术适用于终末期肺病患者，这些患者可能因为存在显著的合并症而不适合手术。本提案的目的是检验这一假设，并将支气管镜减容发展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.