BALTIMORE—When evaluating the appropriateness of surgery for the sickest of patients with emphysema, physicians would do well to remember that the best treatment may not be surgery at all.

Jeffrey M. Drazen, MD, offered that advice in an editorial[1] after reviewing early data from the National Emphysema Treatment Trial (NETT), a five-year, multicenter clinical trial evaluating the efficacy of lung volume reduction surgery (LVRS) versus medical management. Trial investigators have identified a subgroup of emphysema patients who are unlikely to benefit from LVRS and who have a high risk of postoperative death.[2] The finding is so significant that enrollment of these high-risk patients (about one in seven current enrollees) in NETT has been stopped. The overall study is slated to end in 2002.

Patients in the high-risk category had a forced expiratory volume in one second (FEV1) that was 20% or less of predicted and either a carbon monoxide diffusing capacity (DLCO) of no greater than 20% of predicted or evidence of homogeneous emphysema on computed tomography (CT). In the trial, these patients had a 30-day mortality rate of 16% after LVRS versus 0% with medical treatment. Surgery did produce small improvements in exercise capacity, walking distance, and lung function among those who survived for six months or longer. These benefits were not clinically meaningful, though, asserted Dr. Drazen, Chief of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital in Boston. “The operation harmed some [high-risk] patients and did not benefit those who survived,” he stressed.

To be enrolled in NETT, emphysema patients had to have an FEV1 of no more than 45% of predicted, though it had to be at least 15% of predicted in those 70 years or older. Total lung capacity had to be at least 100% of predicted and residual volume at least 150% of predicted.

The resting arterial carbon dioxide tension could be no more than 60 mm Hg (55 mm Hg in Denver) while the patient was breathing room air, while the resting arterial oxygen tension had to be at least 45 mm Hg (30 mm Hg in Denver). Patients also had to be able to walk more than 140 meters in six minutes, pedal for three minutes on a bicycle ergometer without a load, and abstain from smoking for six months before randomization. They were excluded if conditions other than emphysema that precluded surgery or might interfere with follow-up were present. High-resolution chest CT was used to grade the extent of emphysema in both lungs, which were divided into three apical-to-basal zones. Each lung zone received a score of 0 (no emphysema) to 4 (emphysema in more than 75% of the zone). Heterogeneous emphysema was defined as at least a 2-point difference in score among the three zones of one lung. Anything else was considered homogeneous emphysema.

After completing six to 10 weeks of pulmonary rehabilitation, patients who met the enrollment criteria were evaluated to determine their suitability for LVRS. Those randomized to the procedure underwent resection of 20% to 35% of each lung. They resumed pulmonary rehabilitation and medical therapy after surgery. Patients not assigned to surgery simply continued pulmonary rehabilitation and medical therapy.

MORTALITY AND QUALITY OF LIFE

From January 1998 to June 2001, 1,033 emphysema patients were randomized to LVRS or medical management. Of these, 140 were classified as high risk based on their lung function and CT findings. Following randomization, the high-risk patients were evenly split between the surgical and medical groups. One of the patients assigned to LVRS subsequently declined surgery, and four of those randomized to medical treatment underwent LVRS outside the trial.

During the first 30 days after randomization, there were no deaths in the medical group; 11 (16%) of the LVRS patients died during that time. Furthermore, in the surgical group, 30-day mortality rose to 25% among patients with all three high-risk characteristics. The surgical technique used—median sternotomy or video-assisted thoracoscopy—had no effect on 30-day mortality.

During the three and a half years before the study was terminated, 10 (14%) of the medical patients and 33 (47%) of the surgical patients died. When the death rates per person-years of treatment were compared, the overall mortality risk was nearly four times greater in the surgical group than in the medically managed group (0.43 vs 0.11 deaths per person-year, respectively).

Due to varying times of randomization, only 60 surgical and 51 medical high-risk patients were eligible for the six-month outcomes analysis. The results favored neither group. LVRS was linked to a greater risk of death, whereas medical management was associated with a greater likelihood of poor functional outcomes (a few LVRS survivors made substantial gain in functional status).

When the six-month analysis of high-risk patients was confined to survivors, the surgical group demonstrated small gains in exercise capacity, six-minute walk distance, and FEV1, whereas the medical group showed small losses in these measures.

Quality-of-life scores dropped slightly in both groups at six months.

PROCEED WITH CAUTION IN HIGH-RISK PATIENTS

The trial investigators advise cautious use of LVRS in emphysema patients with a low FEV1 and either homogeneous emphysema or a low DLCO. However, some individual high-risk emphysema patients may still opt for surgery despite the risk, Gail Weinmann, MD, told PULMONARY REVIEWS. “They may be willing to accept the mortality risk if there is a chance, however small, of an improved quality of life,” explained Dr. Weinmann, project officer for the National Heart, Lung, and Blood Institute, which sponsored the trial, along with the Centers for Medicare and Medicaid Services.

NETT’s design initially caused some controversy, noted Dr. Drazen, who is also the emeritus Parker B. Francis Professor of Medicine at Harvard Medical School and a member of the Pulmonary Division of the Department of Medicine at Brigham and Women’s Hospital, because many people felt it was unethical to have a group of medically treated controls when LVRS already seemed so effective. “However, some patients who were disappointed when they discovered they were in the control group can now be thankful that this assignment may have saved their lives,” he concluded.

—Timothy Begany

References
1. Drazen JM. Surgery for emphysema—not for everyone. Available at: http://nejm.org/earlyrelease/feature.asp?strxmlfilename=2001/20011011/01101102. Accessed September 7, 2001.
2. National Emphysema Treatment Trial Research Group. Patients at high risk of death after lung-volume–reduction surgery. Available at: http://nejm.org/earlyrelease/feature.asp?strxmlfilename=2001/20011011/01101101. Accessed September 7, 2001.

Return to table of contents