Published in UAB Insight, Winter 2008
UAB Testing Alternatives to Surgical Procedure
Emphysema , a chronic, progressive, largely irreversible disease, affects more than 3 million Americans. The disease will remain a leading cause of morbidity and mortality in the United States for years to come: 46 million Americans smoke despite public health initiatives discouraging cigarette use, the condition’s most common cause. Treatment options are limited, although oxygen therapy, bronchodilators, and steroids can improve quality of life. For patients with advanced disease, lung hyperinflation contributes significantly to symptoms and low exercise tolerance. While lung volume reduction surgery (LVRS) benefits some individuals, the cost and morbidity of major surgery in these patients are compelling investigators to pursue less invasive approaches.
Emphysema causes tissue damage secondary to chronic inflammation, resulting in decreased lung elastic recoil. Combined with expiratory airway collapse, reduced recoil promotes hyperinflation and air trapping in overly compliant emphysematous lungs. Hyperinflation compresses areas of more normal lung, leading to reduced ventilation in the well-perfused lung. “The lung becomes too large and compresses the diaphragm, making it inefficient. This causes dyspnea and fatigue, compromising patients’ quality and length of life,” says pulmonologist Mark T. Dransfield, MD, assistant medical director of the UAB Lung Health Center.
“For a subset of carefully selected patients, LVRS to remove hyperinflated, poorly functional areas of lung is a viable option,” Dransfield says. The National Emphysema Treatment Trial showed that for those with upper lobe–predominant emphysema and low exercise tolerance, LVRS improves pulmonary function, exercise capacity, quality of life, and has a long-term mortality advantage (N Eng J Med. 2003;348:2059-2073).
However, most patients with severe emphysema are not candidates for LVRS. Those with very low (≤20% of predicted) forced expiratory volume in the first second of expiration (FEV1) and a homogeneous pattern of emphysema or a diffusion capacity of the lung for carbon monoxide of ≤20% of predicted are at high risk of death after LVRS. Operative mortality is 4% to 7%, morbidity is 30% to 50%, and hospital stays may last up to 14 days (Semin Thorac Cardiovasc Surg. 2002;14:399-402) and (Semin Respir Crit Care Med. 2005;26:167-191).
Bronchoscopic LVR
Investigators are developing novel approaches and new devices designed to gain the benefits of surgery without general anesthesia and a thoracotomy. Noninvasive bronchoscopic procedures currently being investigated include bronchial fenestration with bypass stents to improve expiratory flow, bronchial occlusion with one-way valves to restrict airflow into lungs, and bronchoscopic instillation of biocompatible biodegradable substances that promote atelectasis.
Implantation of drug-eluting stents that create pathways for air to exit the lungs has shown promise, and bronchial stenting can benefit patients with diffuse or homogenous emphysema while other approaches concentrate primarily on the upper lobes of lungs. A small study recently published in The Journal of Thoracic and Cardiovascular Surgery found that paclitaxel-coated stents reduced hyperinflation and dyspnea and improved pulmonary function (2007;134[4]:974-981). A phase 3 clinical trial is underway at the University of Virginia and other centers to determine whether airway bypass can relieve hyperinflation, improve lung function, and ease dyspnea in patients with diffuse emphysema.
UAB Trials
Trials in progress at UAB include investigations of endobronchial valves (EBV) and biologic lung volume reduction (BLVR). EBVs are small umbrella-shaped devices that, when placed in the upper lung lobes by bronchoscopy, allow air and secretions to escape targeted airways and block air entry. The expiration causes atelectasis of the compromised lung, mimicking results of the surgical procedure. Recently reported findings of a 2-year study of EBVs showed significant improvements in FEV1 and the 6-minute walk test (Sciurba, FC. Endobronchial Valve Significantly Improves Emphysema. Presented at Chest 2007, Annual Meeting of the American College of Chest Physicians; October 22, 2007; Chicago, IL).
A preliminary study of Spiration, Inc’s Intra-Bronchial Valve (IBV) System found valve implantation is a safe and effective option for improving health-related quality of life (J Thorac Cardiovasc Surg. 2007;133:65-73). UAB thoracic surgeon Robert J. Cerfolio, MD, is principal investigator (PI) for the Valve Intervention Treatment Trial, a phase 3 multicenter trial of the IBV System.
Cerfolio is recruiting participants aged 40 to 74 years who have predominantly upper lobe emphysema and severe dyspnea. Patients must stop smoking 4 months prior to the trial and cannot smoke during their participation. Researchers plan to enroll up to 500 participants at as many as 40 sites in the United States for the 6-month study.
“The preliminary results of our earlier phase studies have been quite favorable, and we look forward to assessing the efficacy of these valves in patients with emphysema in a prospective multicenter study,” Cerfolio says.
Dransfield is PI for a low-dose phase 2 clinical trial of the BLVR System by Aeris Therapeutics, Inc for patients with advanced upper lobe–predominant emphysema refractory to medical therapy. The system uses bronchoscopic delivery of a fibrin-based hydrogel to subsegmental bronchi, causing initial collapse and tissue remodeling so that hyperinflated emphysematous lung converts to contracted scar. The hydrogel’s active ingredients include poly-L-lysine acetate to promote scarring and shark sodium chondroitin sulfate to facilitate remodeling and bind to poly-L-lysine.
A phase 1 trial of the hydrogel found improved exercise capacity, lung function, and respiratory symptoms (Chest. 2007;131:1108-1113). “The technique reduces lung volume by permanently collapsing the diseased areas of the lung, providing room within the chest for better function of healthier portions of lung,” Dransfield says. He identifies the most damaged lung areas by computed tomography and targets four segments on each side for treatment. “Measurements 6 weeks postprocedure show improvements in respiratory-specific quality of life, reduction in gas trapping, and improvement in vital capacity, expiratory flow, and inspiratory capacity, as well as relief from dyspnea,” he says. UAB also will participate in a phase 2 study of BLVR for individuals with homogeneous emphysema.
Dransfield screens emphysema patients for all currently available options for lung reduction, including surgery and bronchoscopic LVR procedures, at The Kirklin Clinic®. For select patients, LVRS will be the best course. “We have reduced the morbidity of LVRS significantly with new techniques, found ways to reduce pain, and now favor performing a unilateral approach, which has a very low mortality rate. In fact, I believe this is the preferred approach to LVRS in many patients,” Cerfolio says.
Further clinical trials are necessary to confirm results and pinpoint target doses and refine techniques, Cerfolio says. “Bronchoscopic approaches to lung volume reduction that duplicate results of surgery with reduced mortality and morbidity may be a major development in treating advanced emphysema.”
For more information:
Dr. Mark Dransfield
1.205.934.5425
Dr. Robert Cerfolio
1.877.547.8839