Radiofrequency therapy improves exercise capacity of mice with emphysema.

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.

Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning.

PURPOSE: To investigate the degree to which lung ventilation and gas exchange are regionally correlated, using the emerging technology of hyperpolarized (HP)-129Xe magnetic resonance imaging (MRI). METHODS AND MATERIALS: Hyperpolarized-129Xe MRI studies were performed on 17 institutional review board-approved human subjects, including 13 healthy volunteers, 1 emphysema patient, and 3 non-small cell lung cancer patients imaged before and approximately 11 weeks after radiation therapy (RT). Subjects inhaled 1 L of HP-129Xe mixture, followed by the acquisition of interleaved ventilation and gas exchange images, from which maps were obtained of the relative HP-129Xe distribution in three states: (1) gaseous, in lung airspaces; (2) dissolved interstitially, in alveolar barrier tissue; and (3) transferred to red blood cells (RBCs), in the capillary vasculature. The relative spatial distributions of HP-129Xe in airspaces (regional ventilation) and RBCs (regional gas transfer) were compared. Further, we investigated the degree to which ventilation and RBC transfer images identified similar functional regions of interest (ROIs) suitable for functionally guided RT. For the RT patients, both ventilation and RBC functional images were used to calculate differences in the lung dose-function histogram and functional effective uniform dose. RESULTS: The correlation of ventilation and RBC transfer was ρ = 0.39 ± 0.15 in healthy volunteers. For the RT patients, this correlation was ρ = 0.53 ± 0.02 before treatment and ρ = 0.39 ± 0.07 after treatment; for the emphysema patient it was ρ = 0.24. Comparing functional ROIs, ventilation and RBC transfer demonstrated poor spatial agreement: Dice similarity coefficient = 0.50 ± 0.07 and 0.26 ± 0.12 for the highest-33%- and highest-10%-function ROIs in healthy volunteers, and in RT patients (before treatment) these were 0.58 ± 0.04 and 0.40 ± 0.04. The average magnitude of the differences between RBC- and ventilation-derived functional effective uniform dose, fV20Gy, fV10Gy, and fV5Gy were 1.5 ± 1.4 Gy, 4.1% ± 3.8%, 5.0% ± 3.8%, and 5.3% ± 3.9%, respectively. CONCLUSION: Ventilation may not be an effective surrogate for true regional lung function for all patients.

Sparing healthy lung by focusing the radiation beam flow onto the emphysematous regions in the treatment of lung cancer.

INTRODUCTION: Currently, routine radiotherapy (RT) planning for locally advanced lung cancer (LC) does not take into consideration the functional state of the lung. The goal of this study was to determine if it is technically feasible to integrate the sites of pulmonary emphysema (PE) into the RT planning process. METHODS: Ten patients with LC and PE treated with helical Tomotherapy© were retrospectively included. After extraction by Myrian© software based on diagnostic CT (DCT), the PE data were transferred to the treatment planning system (TPS). PE-optimized plans were performed for patients with significant PE, where the dose was focused onto the PE. We compared the PE-optimized RT plans to the initial RT plans. RESULTS: The median dose to the planning target volume (PTV) was 52 Gy (range, 36-66) in fractions of 2-3 Gy. The median PE volume was 220 cm3 (range: 12-1394), and six patients were eligible for a PE-optimized RT plan. Considering the lung without PE, the V20 and V30 variations were not significant (P > 0.05), the V5 decreased from 50% to 44% after re-planning (P < 0.05). The mean PTV D98 was 50 Gy versus 48 Gy (P < 0.05). CONCLUSION: Focusing the RT beam flow on the PE structure rather than the healthy lung appears feasible, and may be a promising technique to help preserve pulmonary function and minimize RT-related pulmonary toxicity.

Delayed noninvasive reduction of large bullae following thoracic irradiation.

Chest radiotherapy is a mainstay of management of thoracic oncology patients. Radiotherapy also injures nontarget tissues such as the lungs, coronary arteries, and esophagus, and safe limits to the doses that can be delivered to tumors have been determined empirically. Patients afflicted with lung cancer due to smoking often have concomitant chronic obstructive pulmonary disease which, on occasion, manifests as bullous emphysema. We describe a case and course of treatment of lung cancer found incidentally in a patient followed for severe pulmonary emphysema. Treatment consisted of radiochemotherapy after induction chemotherapy. Three years after the end of antineoplastic treatment, a follow-up computed tomography scan revealed complete retraction of a large emphysematous bulla that had been present prior to treatment.

Experimental ablation of emphysematous rat lung with Nd: YAG laser: lung changes studied by histopathology and SEM.

Laser ablation has been employed as a therapeutic measure for chronic pulmonary emphysema. As yet, however, its effect is not understood on firm pathological basis. We aimed to study, both histopathologically and using Scanning Electric Microscopy (SEM), the changes produced by irradiation with contact Neodymium-yttrium aluminum garnet laser (Nd: YAG laser) in rat lungs with experimentally induced emphysema. Emphysema was produced in 34 rats by instilling elastase via airways. Eight weeks after the instillation, the emphysematous left lung was irradiated under thoracotomy with contact Nd: YAG laser at a power of 5 watts. The animals were sacrificed in acute as well as chronic phase for histopathological observation of lung and scanning electron microscopy. Laser caused necrotic and inflammatory changes in the subpleural zone of lung. Immediately after irradiation, the alveolar septa were destroyed as visualized by SEM, only leaving the elastic skeleton. In a chronic phase, the necrotic zone was collapsed and replaced with a thick fibrous scar which seemed to serve more or less to keep the organ from being excessively inflated. In this model, irradiation induces subpleural dense scarring, which, by "encasing" an emphysematous lung, is expected to more or less normalize the excessive compliance.

Clinical improvement of patients with emphysema after radiotherapy.

In advanced emphysema the reduced lung retractive force permits dynamic compression of the airways during expiration; this gives rise to breathlessness which is often refractory to conventional remedies. Radiotherapy causes shrinkage of lung tissue and has therefore been given as treatment to 10 patients with emphysema. They have been followed for two years, during which time three have died from various causes, but no adverse effect of radiotherapy has been observed. All the patients at some time experienced a reduction in breathlessness on exertion and an increase in the range of their daily activities; the distensibility of their lungs was on average reduced but the response to test exercise was not altered. The possibility that the clinical improvement may have been a placebo effect is now being investigated.