Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.
Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.
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DOI：
10.1371/journal.pcbi.1005282
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发表时间：
2017-02
影响因子：
4.3
通讯作者：
Suki B
中科院分区：
文献类型：
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作者：
Mondoñedo JR;Suki B
肺减容手术 (LVRS) 和支气管镜肺减容手术 (bLVR) 是姑息治疗，旨在减少晚期肺气肿的过度充气。之前的工作已经评估了这些技术的功能改进和生存优势，尽管它们对肺部微机械环境的影响尚未确定。在这里，我们引入了一个计算模型来模拟代表肺气肿进展的弹性网络的基于力的破坏，我们用它来通过 LVRS 和 bLVR 跟踪对肺容量减少的反应。我们发现（1）可以根据术前网络结构预测 LVRS 疗效； (2) bLVR 后宏观功能的改善与机械力不均匀性的微观变化有关； (3)这两种技术都改善了受肺顺应性影响的生存和生活质量，尽管同时加速了疾病进展。我们的模型预测对肺容量减少前后肺气肿进展的微观起源产生了独特的见解。手术和最近的支气管镜肺减容术是晚期肺气肿患者唯一可用的治疗方法。几项大规模临床研究已经根据患者的治疗结果概述了适当的选择标准；然而，决定疾病进展和对这些治疗的反应的潜在机制尚不清楚。为了回答这个问题，我们开发了一个肺部网络模型来比较每种治疗的即时和长期反应。这种方法使我们能够直接研究与局部结构和力学环境的微观变化相关的宏观功能变化。此外，它有助于在相同初始条件下直接比较手术和支气管镜肺减容术，这在临床研究中是不可行的。我们在这里提出了一种机制，表明肺减容功效与肺内微观力不均匀性的变化密切相关。对导致肺气肿的机制的这种了解有可能通过更合理、针对患者的治疗策略极大地改善目前对该病的治疗。
Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. Surgical and, more recently, bronchoscopic lung volume reduction is the only available treatments for patients with advanced stage emphysema. Several large-scale, clinical studies have outlined appropriate selection criteria based on patient outcomes; however, the underlying mechanisms determining disease progression and response to these treatments are not well-understood. To answer this question, we have developed a network model of the lung to compare immediate and long-term response to each treatment. This approach allows us to directly study macroscopic changes in function related to microscopic changes in the local structural and mechanical environment. In addition, it facilitates direct comparisons between surgical and bronchoscopic lung volume reduction given identical initial conditions, which is not feasible in a clinical study. We propose here a mechanism suggesting that lung volume reduction efficacy is intimately linked to changes in microscopic force heterogeneity within the lung. Such an understanding of the mechanisms driving emphysema has the potential to greatly improve current therapies for this condition through more rationalized, patient-specific treatment strategies.