Departments: Interventional Pulmonology in Other Journals
A Randomized Trial Comparing LVRS with Medical Therapy for Severe Emphysema
N Engl J Med. 2003;348:2059–2073. National Emphysema Treatment Trial Research Group, NETT Coordinating Center, Baltimore, MD.
This publication reports the results of the federally sponsored, multicenter, randomized clinical study, the National Emphysema Treatment Trial (NETT), involving a total of 1218 patients with severe emphysema, at 17 medical centers in the United States, who underwent pulmonary rehabilitation and were randomly assigned to undergo lung-volume-reduction (LVRS; n = 608) or to receive continued medical therapy (MT; n = 610). The patients with severe emphysema underwent comprehensive medical evaluation to ensure compliance with usual MT and to rule out clinically significant coexisting conditions. Baseline measurements were completed after pulmonary rehabilitation but before randomization, and patients underwent complete evaluations at 6 months, 12 months, and yearly thereafter. Overall mortality and maximal exercise capacity (on cycle ergometry with an increment of 5 or 10 W per minute after 3 minutes of pedaling with the ergometer set at 0 W and the patient breathing 30% oxygen) were the primary outcome measures. Secondary outcome measures included pulmonary function, the distance walked in 6 minutes, and the results on a self-administered questionnaire about health-related quality of life, a general quality-of-life questionnaire (the Quality of Well-Being scale), and a dyspnea questionnaire. An important goal of the trial was to identify patient-selection criteria for LVRS. Criteria for inclusion were designed to include all patients who might benefit from LVRS. Patients with an FEV1 ≤20% of the predicted value and either a homogeneous distribution of emphysema or a DLCO ≤20% of the predicted value were determined to be at high risk for death after LVRS (based on an earlier study), and were no longer eligible for randomization. The analysis of results revealed that the overall mortality was 0.11 death per person-year in both treatment groups (risk ratio for death in the LVRS group, 1.01; P = 0.90). The overall mortality in the LVRS group was 0.09 death per person-year as compared with 0.10 death per person-year in the MT group (risk ratio, 0.89; P = 0.31); exercise capacity after 24 months had improved by more than 10 W in 16% of patients in the LVRS group as compared with 3% of patients in the MT group (P < 0.001). Among patients with predominantly upper-lobe emphysema and low exercise capacity, mortality was lower in the LVRS group than in the MT group (risk ratio for death, 0.47; P = 0.005). Among patients with non-upper-lobe emphysema and high exercise capacity, mortality was higher in the LVRS group than in the MT group (risk ratio, 2.06; P = 0.02). The authors concluded that overall, LVRS increases the chance of improved exercise capacity but does not confer a survival advantage over MT. They also indicate that LVRS yields a survival advantage for patients with both predominantly upper-lobe emphysema and low baseline exercise capacity. Another conclusion was that patients previously reported to be at high risk and those with non-upper-lobe emphysema and high baseline exercise capacity are poor candidates for LVRS because of increased mortality and negligible functional gain. This continuation of NETT trials provides further insights into the optimal selection of patients who might benefit from LVRS. Even though LVRS was associated with a greater chance of improvement in exercise capacity, lung function, quality of life, and dyspnea, the overall mortality was similar in the LVRS and MT groups when the previously identified high-risk patients were excluded (FEV1 ≤20% predicted, and either homogeneous emphysema or a DLCO ≤20% predicted). To summarize, 1) patients with predominantly upper-lobe emphysema and a low maximal workload after rehabilitation had lower mortality, a greater probability of improvement in exercise capacity, and a greater probability of improvement in symptoms if they underwent LVRS than if they received MT alone; 2) patients with predominantly non-upper-lobe emphysema and a high maximal workload after rehabilitation had higher mortality if they underwent LVRS than if they received MT alone, and they had little chance of functional improvement regardless of the treatment they received; and 3) overall, LVRS offered no reduction in mortality during an average of 29 months of follow up.