Physiological Modeling of Responses to Upper Versus Lower Lobe Lung Volume Reduction in Homogeneous Emphysema

Axel Kempa,Arschang Valipour,Franz Stanzel,Sherwin Asadi,Oren Fruchter,Edward P Ingenito,Felix J Herth,Mordechai R Kramer,Ralf Eberhardt

doi:10.3389/fphys.2012.00387

Abstract

Rationale: In clinical trials, homogeneous emphysema patients have responded well to upper lobe volume reduction but not lower lobe volume reduction. Materials/Methods: To understand the physiological basis for this observation, a computer model was developed to simulate the effects of upper and lower lobe lung volume reduction on RV/TLC and lung recoil in homogeneous emphysema. Results: Patients with homogeneous emphysema received either upper or lower lobe volume reduction therapy based on findings of radionucleotide scintigraphy scanning. CT analysis of lobar volumes showed that patients undergoing upper (n = 18; −265 mL/site) and lower lobe treatment (LLT; n = 11; −217 mL/site) experienced similar reductions in lung volume. However, only upper lobe treatment (ULT) improved FEV1 (+11.1 ± 14.7 versus −4.4 ± 15.8%) and RV/TLC (−5.4 ± 8.1 versus −2.4 ± 8.6%). Model simulations provided an unexpected explanation for this response. Increases in transpulmonary pressure subsequent to volume reduction increased RV/TLC in upper lobe alveoli, while caudal shifts in airway closure decreased RV/TLC in lower lobe alveoli. ULT, which eliminates apical alveoli with high RV/TLC values, lowers the average RV/TLC of the lung. Conversely, LLT, which eliminates caudal alveoli with low RV/TLC values, has less effect. Conclusion: LLT in homogeneous emphysema is uniformly less effective than ULT.

Highlights

Surgical lung volume reduction (LVRS) in patients with homogeneous emphysema has been shown to improve physiology and functional outcomes, responses are generally smaller than in patients with heterogeneous upper lobe disease (Weder et al, 2009)
Conceptually, lung volume reduction therapy (LVRT) is a straightforward procedure that involves reducing the quantity of hyperinflated lung by eliminating damaged tissue
A simple but elegant physiological model to explain the effects of LVRT on airflow limitation in advanced emphysema was proposed over a decade ago by Fessler and Permutt (1998)

Summary

Introduction

Surgical lung volume reduction (LVRS) in patients with homogeneous emphysema has been shown to improve physiology and functional outcomes, responses are generally smaller than in patients with heterogeneous upper lobe disease (Weder et al, 2009). Independent of the distribution of disease in any given patient, LVRS generally involves resection of tissue in the upper lobes due to limited surgical access to lower lobe sites (DeCamp et al, 2008). AeriSeal® Emphysematous Lung Sealant (ELS) is a novel endoscopic lung volume reduction (ELVR) treatment shown to improve pulmonary function in patients with advanced emphysema (Herth et al, 2011a). While ELS improves lower lobe access, physiological benefit in homogeneous emphysema patients has been limited almost exclusively to those treated in the upper lobes. This study describes the development of a physiological model that explains why patients with advanced homogeneous emphysema who receive lower lobe ELVR are less likely to benefit than those treated in the upper lobes

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Discussion

Conclusion