Abstract

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in “volume reduction” and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.

Highlights

  • H & E Hematoxylin and eosin Lm Mean linear intercept length standard error of the mean (SEM) Standard error of the mean

  • Lung volume reduction surgery (LVRS) is a potential treatment for Chronic Obstructive Pulmonary Disease (COPD), but it is limited to a subpopulation of patients with severe emphysema involving the upper lobes and with low exercise capacity

  • Lowing reasons: four (2 each in the emphysema and emphysema + treatment group) experienced over 20% body weight loss and 2 mice in the emphysema group became ill during the course of the experiment

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Summary

Introduction

H & E Hematoxylin and eosin Lm Mean linear intercept length SEM Standard error of the mean. Smoking-related COPD is accompanied by emphysema, which is characterized by the destruction of lung tissue resulting in the loss of alveolar integrity, enlargement of the alveolar spaces, poor gas exchange, and airway collapse due to the loss of elastic r­ ecoil[3]. This remodeling results in impairment in airflow and hypoxemia. A well-known pathologic feature of emphysema is pulmonary vascular remodeling, which causes diminution of blood flow to the emphysematous ­regions[15], making these areas susceptible to thermal injury Based on these concepts, we applied RF therapy extracorporeally to destroy emphysematous regions of the COPD lung in a rodent model of emphysema. We investigated the effectiveness of extracorporeal RF treatment in improving the exercise capacity of mice with emphysema

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