Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema

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.Author Summary: 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.