Determining who would most benefit from lung-volume–reduction surgery is a central goal of the National Emphysema Treatment Trial.
The phone is ringing off the hook at New York’s Center for Lung Failure, Columbia-Presbyterian Medical Center–as it is at all 18 of the clinical centers nationwide participating in the National Emphysema Treatment Trial (NETT). Most of the centers are accepting patients for screening, and, patient coordinators say, the referral calls have been coming in almost nonstop. "Actually, we haven’t even done any advertising yet–it’s just been word of mouth through the patients’ physicians," says Fran Brogan, RN, NETT clinical coordinator at Columbia-Presbyterian.
Patients have obvious reasons for wanting to participate in the trial of lung-volume-reduction surgery (LVRS), a procedure aimed at improving quality of life and reversing the progression of end-stage lung disease. The 5-year NETT study is being conducted to address the overall efficacy of LVRS, particularly in comparison with medical management and pulmonary rehabilitation. The study aims to enroll 4,500 patients. Of those, 2,600 will be invited to participate in the randomized trial. All trial participants will receive intensive medical therapy and rehabilitation. Half will also be randomly selected to undergo LVRS.
In addition to studying the surgery’s efficacy, one of the trial’s central goals is to determine appropriate patient-selection criteria for LVRS. "It’s very important," says Abby Krichman, RRT, patient referral coordinator for the NETT trial at Duke University Medical Center, in Durham, NC. "You’re trying to take a group of patients who are severely ill in the first place, and then you’re trying to characterize even further who will and who will not benefit from a major intervention," Krichman says. "We know that not everybody with emphysema is going to benefit from this type of surgery." Clinicians have theories about the type of patient who will benefit most from LVRS based on the procedures performed at their individual centers, Krichman notes, but no standardized criteria exist.
One difficulty in determining patient-selection criteria is the fact that patients display such different lung disease patterns, Krichman says. "Some patients have just pure emphysema with no asthma component, some patients have a lot of asthma component. Some people have bronchitis on top of their emphysema. Some people have bad disease all over their lungs, some only have it in the upper part of their lungs," she says. This can make standardization of selection criteria difficult for a procedure like LVRS.
Some studies have attempted to correlate disease pattern with LVRS outcome. In one study,1 154 patients who underwent LVRS after an evaluation that involved pulmonary function (PF) testing, arterial blood gas measurement, and chest radiography were analyzed. These patients were selected out of a larger group to receive LVRS based on the presence of heterogeneous emphysema as displayed on chest computed tomography (CT) and lung perfusion scans. The study authors found that upper-lobe heterogeneous emphysema was strongly associated with improved outcomes after the procedure, and noted that additional clinical and physiological factors did not further impact outcomes. The lack of broad-based, multicenter research, however, makes the overall accuracy of such results difficult to ascertain.
One goal in choosing patients for the NETT is to give researchers a broad base of emphysema patients to facilitate efficacy and benefit comparisons. "We’ve tried to include as many patients as we possibly could," Krichman says.
The Initial Criteria
Patients accepted to participate in the NETT must meet an extensive series of administrative, physical, and lifestyle criteria. Generally, patients whose overall health would make major surgery unsafe or ineffective are ruled out. Notably, the patient must have bilateral severe emphysema and must be eligible for Medicare because the NETT is sponsored in part by HCFA, which hopes to determine the cost-effectiveness as well as the efficacy of the procedure. After contacting a center, patients are required to submit medical records for preliminary assessment. "We meet on a weekly basis and review all of the records to determine whether someone should spend the time to come up to Durham for a week to get evaluated," Krichman says. (See Table 1, page 56, for NETT- qualifying criteria.)
Likely candidates then visit a NETT center for a full week of testing. Brogan says the week features a variety of clinical and functional tests, including PF tests; a CT scan; a stress test; a cardiopulmonary exercise test; oxygen titration; a 6-minute walk test; a biochemical validation of nonsmoking; and several quality-of-life measurements.
"Results from any of these tests can exclude a patient from the study," Brogan says. Some patients who can improve their function or clinical health on their own may return for a second round of evaluations. "There are absolute criteria that will exclude you–that is, if you’ve had coronary artery bypass graft surgery before, we’re not going to have you come back," Krichman says. "But somebody who is just weak and debilitated and didn’t know about rehabilitation can do something about that. They can come back 6 months later or even 2 months later and get reevaluated."
The patient selection criteria will exclude individuals with a Po2 less than 45 or a pco2 greater than 60, for example. If individuals who participate in pulmonary rehabilitation outside the trial manage to improve their oxygen titration levels, the NETT may reconsider their application. These patients must still undergo the week-long initial evaluation. "Also, part of the evaluation week assesses their functional capabilities–can they even do the rehabilitation? Some people can’t," Krichman says. "They’re in a wheelchair, they can’t even get up, they can’t do a 6-minute walk test, they can’t do any of those things. We would tell them that they need to go back home and get into a local rehab program to build their strength back up."
Age is not a factor in determining whether a patient is eligible for participation in the NETT, although Brogan says patients aged 70 or older face stricter PF criteria. In fact, Krichman says, most of the patients accepted are aged 60 or greater, and "just don’t have any other options."
Quality of life is assessed in a series of
7 or 8 tests, Krichman says, including the Beck depression inventory and the SP-36. These evaluations will continue at intervals throughout the study, but Krichman points out that "none of the quality-of-life issues will exclude somebody–it’s all physiologic exclusions. We do them during the week-one evaluation, but that’s basically to evaluate if someone is at baseline and how they’re feeling."
One lifestyle choice that means instant disqualification is smoking. "We do measure serum cotinine levels in patients when they initially come in, and ask if they’ve smoked in the past 4 months," Krichman says. If they have a positive serum cotinine level, they are not accepted into the trial.
Evaluation and selection assessment do not stop once a patient has passed the first round of tests. A patient becomes an official study participant only after randomization, which occurs after a preliminary pulmonary rehabilitation period and a second evaluation. Krichman points out that every patient who takes part in the initial rehabilitation phase will join a registry of emphysema patients, which, she says, "is probably going to be the largest registry on emphysema patients ever." Patients must complete this rehabilitation phase regardless of whether they ultimately are randomized to receive LVRS.
Although the NETT seeks to compare LVRS with a combined medical management and pulmonary rehabilitation program, it places great emphasis on pulmonary rehabilitation and on first seeing whether other modes of intervention might be more beneficial. "Sometimes we’ll end up finding little nodules or spots on people’s lungs that they would not otherwise have known were there," Krichman says. Some of these individuals are more likely candidates for lung transplantation, she says, noting, "In any case, we’ll get them to wherever they need to go."
Another goal of the NETT is to determine whether rehabilitation can improve a patient’s quality of life. A previous study2 conducted at the University of California San Diego Medical Center, one of the current NETT clinical centers, retrospectively evaluated pulmonary rehabilitation’s role in LVRS. It found that 55 percent of patients referred for LVRS consideration had never participated in pulmonary rehabilitation, and 46 percent of referred candidates were sent instead to a rehabilitation program. On the basis of these discoveries, the center now relies on pulmonary rehabilitation as a primary tenet of its comprehensive emphysema and chronic obstructive pulmonary disease management program.
The NETT protocol calls for each patient to undergo pulmonary rehabilitation upon entering the study, including education, regardless of his/her health status. Core rehabilitation, which takes place for 4 days during the first week of rehabilitation, must be conducted at the enrolling clinical center. The remaining rehabilitation sessions, scheduled for 3 days a week, may take place at a certified satellite center, Brogan says. "There are different levels, but the rehabilitation is basically the same. If, for instance, they’ve had rehabilitation before and have done well, they’ll just go the minimum of 6 weeks."
Once patients finish pulmonary rehabilitation, they complete a second, shorter series of clinical and functional tests, including a PF test, an exercise test, oxygen titration, a 6-minute walk test, and a perfusion scan, Brogan says. Finally, if the patient is in good health and does not fit any of the exclusion parameters, he/she is randomized to receive ongoing pulmonary rehabilitation and either continuing medical therapy or LVRS.
Establishing the Criteria
It took approximately 9 months to finalize the patient-selection criteria used in the NETT, Krichman says. "You’re talking about two physicians at 18 centers, so you’re talking 36 physicians who have their own ideas about what should be done," she notes. Most of the study’s physician investigators have a pulmonary medicine or thoracic surgery background, so they discussed issues such as rehabilitation, exercise physiology, and PF testing to the minutest detail. In the end, though, Brogan and Krichman say that the NETT patient-selection criteria mirror those used by their respective centers for any patient. "Nothing is glaringly different from what any of the centers would normally do," Krichman says.
Kathryn Olson is a contributing writer for RT.
1. McKenna RJ Jr, Brenner M, Fischel RJ, et al. Patient selection criteria for lung volume reduction surgery. J Thorac Cardiovasc Surg. 1997;114:957-964.
2. Colt HG, Ries AL, Brewer N, Moser K. Analysis of chronic obstructive pulmonary disease referrals for lung volume reduction surgery. The University of California San Diego Emphysema Treatment Group.J Cardiopulm Rehabil. 1997;17:248-252.