Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the U.S. and resulted in 638,000 hospital discharges in 2004, according to the National Center for Health Statistics. But treatment options for this common condition are limited, especially for late-stage disease. Lung volume reduction surgery and lung transplantation can help patients with emphysema, but both procedures are invasive and have substantial associated risks. Researchers are working on developing new treatments, such as injectable gel and airway bypass. Now, another new alternative may soon be available.
At the American College of Chest Physicians' annual meeting in October 2006, researchers presented the results of a preliminary multicenter trial evaluating a one-way “umbrella” valve that limits ventilation in diseased areas of the lung. Researchers at nine medical centers used flexible bronchoscopy to implant 520 valves (an average of six to seven valves per patient) in 75 patients with severe upper-lobe COPD. The response was encouraging: Complications decreased and symptoms improved in approximately 60% of patients.
Atul C. Mehta, FACP, vice chairman of pulmonary, allergy and critical care medicine at the Cleveland Clinic in Cleveland and a coauthor of the study, recently spoke with ACP Hospitalist about the implications of this research.
Q: What were the main goals of the study?
A: The main goal of the trial was to prove the safety of this valve, which we use in patients with severe COPD/emphysema to reduce the size of the expanded lungs. The purpose is to place this valve so that the air trapped inside the lungs will come out but will not go back in. At the same time, we were looking at improvement in the quality of life in patients undergoing valve placement.
Q: Did you meet your goals?
A: Yes, the primary goals were achieved. It is very safe to place the valve for the duration of the trial, and the quality of life improved by 4 points on the St. George's Respiratory Questionnaire.
Q: And now you are going to do a longer trial?
A: The next step is a longer multicenter trial with more than 300 patients. Here the goal would be more looking at objective parameters for improvement in lung function, improvement in exercise endurance and quality of life, once again. It is also possible that we will be looking at radiographic parameters.
We are still deciding what parameters we want to look at. Many of the trials look at the very simple parameter of FEV1, which may not be a good parameter to look at in these patients. The purpose is to reduce the volume, and the CT volumetrics will help us. We may look at those as well. We collect all the information from the spiral CT, and we do three-dimensional reconstruction of the lung and measure the volume of the lung in that fashion. That is what would probably be done in the next trial.
Q: In the future, will you also be looking at mortality data?
A: Yes. The National Emphysema Treatment Trial (NETT) [which tested the effectiveness of lung volume reduction surgery] showed improvement in mortality in a selected group of patients with emphysema. It's a difficult question, but patients need to be followed for a very long time. As the data were being collected [in NETT], we found a survival benefit in one particular group of patients. In the current trial, we don't know which group was doing better. [When we look at the results of valve placement in] all patients together, [valve placement] probably does not improve mortality. There might be some patients in whom this procedure could be risky and some in whom it could be beneficial. Some patients develop a tension pneumothorax [during the procedure] and die. That is going to reduce the survival rates. We need to do the analysis and find which group of patients does better, and which have higher mortality.
Q: How do you know how many valves to place? Is this a decision you make while doing the bronchoscopy, or do you do a CT before the procedure?
A: Because there is not much to decide once you do the bronchoscopy and because we are looking at areas of destruction and areas of hyperinflation, that information comes mainly from the CT scan. We actually select patients based on the CT scan [findings]. If a patient has homogeneous disease, that patient is not a good candidate. We are not doing [this] in patients with a-1 antitrypsin deficiency. When we go to do the bronchoscopy, the decision is already made. Also, there are limitations in that we do not want to go into too many areas. We limit ourselves only to the upper lobes.
Q: Are you working on other treatments?
A: We are also going to start trials with tissue modifiers and tissue engineering, including fibrinogen growth factors. Another option is bronchial fenestration in airways. We put a tiny needle through the bronchoscope and put a hole in the bronchus near the bullae. Then we go over it with a balloon and dilate it, then create a 3-mm opening so the bullae are directly draining into the airway.
Q: Do patients have to commit to smoking cessation in order to undergo these procedures?
A: I run the lung transplant program at the Cleveland Clinic, and [patients] must be smoke-free for at least six months to be listed for lung transplantation or to participate in these clinical trials. Unfortunately, there are some patients who go back to smoking. If all patients stopped smoking, we would not need all these technological advances.