INTERVENTIONAL PULMONOLOGY IN OTHER JOURNALS: Commentary on Selected Publications
Patients at high risk of death after lung-volume–reduction surgery.
N Engl J Med 2001;345:1075–83. NETT Coordinating Center, Baltimore, Maryland, U.S.A. National Emphysema Treatment Trial Research Group.
In this randomized, multicenter (n = 17) clinical trial (National Emphysema Treatment Trial, or NETT) comparing lung-volume–reduction surgery (LVRS) with medical treatment, a total of 1,033 patients were randomized by June 2001. The inclusion criteria into NETT were as follows: Forced expiratory volume in one second (FEV1) less than 45% predicted but more than 15% predicted among patients 70 years of age or older, total lung capacity more than 100% predicted, residual volume more than 150% predicted, partial pressure of arterial carbon dioxide ≤ 60 mmHg at rest and breathing room air, partial pressure of arterial oxygen ≥ 45 mmHg at rest and breathing room air, ability to walk more than 140 m in 6 minutes, ability to complete 3 minutes pedaling on a bicycle ergometer, and abstinence from smoking for 6 months before randomization. Patients had to complete a carbon monoxide diffusing capacity (DLCO) measurement but were not excluded on the basis of the value. The severity and distribution of emphysema were determined from high-resolution computed tomographic (CT) scans of the chest obtained during full inspiration. The extent of emphysema was graded from 0 to 4, with a grade of 0 indicating no emphysema and a grade of 4 indicating the presence of emphysema in more than 75% of the lung zone. Patients who met the enrollment criteria had to complete 6 to 10 weeks of pulmonary rehabilitation, after which the participating center's pulmonologist and surgeon, in consultation with an anesthesiologist and, if necessary, a cardiologist, had to determine whether the patient was a suitable candidate for LVRS. Patients who were assigned randomly to undergo LVRS underwent bilateral surgery by means of either a median sternotomy or video-assisted thoracoscopy. The goal was to resect 20 to 35% of each lung. After surgery, patients continued rehabilitation and medical treatment. Patients were excluded if they had other medical conditions that made them unsuitable for surgery or that might interfere with follow-up. Of the 1,033 patients who were enrolled by June 2001, there were 69 patients who had an FEV1 less than 20% of the predicted value, and either a homogeneous distribution of emphysema on chest CT or DLCO less than 20% of the predicted value. In these 69 patients, the 30-day mortality rate after LVRS was 16%, compared with a mortality rate of 0% among 70 medically treated patients (p < 0.001). Among these high-risk patients, the overall mortality rate was higher in surgical patients than in medical patients (0.43 deaths per person-year vs. 0.11 deaths per person-year). After 6 months, only 33% of the patients in the LVRS group had an improvement in exercise capacity, 23% had either no change or a decrease in exercise capacity, 8% were unable to complete testing, and 35% had died. The health-related quality of life improved in only 28% of these patients, with 72% either dying or having no change or a decrease in the quality of life. The medical therapy group had a higher percentage of poor functional outcomes but fewer deaths. When compared with medically treated patients, survivors of LVRS had small improvements at 6 months in maximal workload (p = 0.06), the distance walked in 6 minutes (p = 0.03), and FEV1 (p < 0.001), but a similar health-related quality of life. The results of the analysis of functional outcomes for all patients, which accounted for deaths and missing data, did not favor either treatment. The authors conclude that caution is warranted in the use of LVRS in patients with emphysema who have a low FEV1 and either homogeneous emphysema or a very low DLCO, because these patients are at high risk for death after surgery and also are unlikely to benefit from the surgery. LVRS consists of surgical resection of 20 to 35% of the emphysematous lung parenchyma. Earlier reports indicated that LVRS is a potentially valuable treatment for patients with advanced emphysema. These studies showed that in general, lung function, exercise capacity, and the quality of life improve after surgery. However, the results have varied. The surgical mortality rate is considerable, with reported rates ranging from 4 to 15%, and with both 6-month and 1-year mortality as high as 17%. The main goals of the NETT are to compare survival rates and exercise capacity 2 years after LVRS with the results from medical therapy, and to identify selection criteria for LVRS. These results were released earlier because of the high mortality rates associated with LVRS. As a result, the NETT has now modified the protocol to exclude high-risk patients, defined as those with an FEV1 less than 20% of that predicted, and either a homogeneous distribution of emphysema on chest CT or DLCO less than 20% predicted. Because of the generally unfavorable outcomes, the NETT no longer enrolls such patients in the clinical trial. As the accompanying editorial indicates, LVRS is not appropriate for everyone with emphysema (N Engl J Med 2001;345:1126–8 ). Whether the patients who survived LVRS in this NETT program will continue to enjoy reduced respiratory symptoms and a better quality of life will be answered after 2 to 3 years.