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Substantial information regarding the role of lung volume reduction surgery (LVRS) in severe emphysema emanates from the National Emphysema Treatment Trial (NETT). The NETT was not a crossover trial and therefore was able to examine the effects of optimal medical management and LVRS on short- and long-term survival, as well as lung function, exercise performance, and quality of life. The NETT generated multiple insights into the preoperative, perioperative, and postoperative management of patients undergoing thoracotomy; described pain control techniques that were safe and effective; and emphasized the need to address nonpulmonary issues to optimize surgical outcomes. After the NETT, newer investigation has focused on bronchoscopic endobronchial interventions and other techniques less invasive than LVRS to achieve lung reduction. In this review, we summarize what we currently know about the role of LVRS in the treatment of severe emphysema as a result of insights gained from the NETT and provide a brief review of the newer techniques of lung volume reduction.

Rationale: To determine the effect of medical treatment versus lung volume reduction surgery (LVRS) on pulmonary hemodynamics.

Methods: Three clinical centers of the National Emphysema Treatment Trial (NETT) screened patients for additional inclusion into a cardiovascular (CV) substudy. Demographics were determined, and lung function testing, six-minute-walk distance, and maximum cardiopulmonary exercise testing were done at baseline and 6 months after medical therapy or LVRS. CV substudy patients underwent right heart catheterization at rest prerandomization (baseline) and 6 months after treatment.

Measurements and Main Results: A total of 110 of the 163 patients evaluated for the CV substudy were randomized in NETT (53 were ineligible), 54 to medical treatment and 56 to LVRS. Fifty-five of these patients had both baseline and repeat right heart catheterization 6 months postrandomization. Baseline demographics and lung function data revealed CV substudy patients to be similar to the remaining 1,163 randomized NETT patients in terms of age, sex, FEV1, residual volume, diffusion capacity of carbon monoxide, PaO2, PaCO2, and six-minute-walk distance. CV substudy patients had moderate pulmonary hypertension at rest (\documentclass[10pt]{article} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{pmc} \usepackage[Euler]{upgreek} \pagestyle{empty} \oddsidemargin -1.0in \begin{document} \begin{equation*}\overline{Ppa}\end{equation*}\end{document}, 24.8 ± 4.9 mm Hg); baseline hemodynamic measurements were similar across groups. Changes from baseline pressures to 6 months post-treatment were similar across treatment groups, except for a smaller change in pulmonary capillary wedge pressure at end-expiration post-LVRS compared with medical treatment (−1.8 vs. 3.5 mm Hg, p = 0.04).

Conclusions: In comparison to medical therapy, LVRS was not associated with an increase in pulmonary artery pressures.

Emphysema is disabling and progressive and hallmarked by decreased exercise tolerance and impaired quality of life. Hyperinflation is the sentinel physiological characteristic of emphysema that is responsible for exercise intolerance, dyspnea, impaired quality of life and high mortality. Medical treatment does not alter the progression of emphysema and has little effect on palliating dyspnea or improving functional performance or quality of life. Surgical interventions that reduce lung volume have been the focus of multiple interventions for decades; however, until recently, limited evidence has documented their effectiveness. Lung volume reduction surgery (LVRS) underwent rigorous study in the National Emphysema Treatment Trial (NETT), which demonstrated its short and long term effectiveness, associated morbidity and mortality and the essential factors that predict LVRS success or failure. Current investigation focuses on the use of less invasive techniques, predominantly bronchoscopic techniques that reduce lung volume without open thoracotomy. Herein, I summarize the major results of the NETT and briefly review newer bronchoscopic lung volume reduction techniques that show promise as alternative treatments for select COPD patients undergoing consideration for lung transplantation.

The objective of lung volume reduction surgery (LVRS) is the safe, effective, and durable palliation of dyspnea in appropriately selected patients with moderate to severe emphysema. Appropriate patient selection and preoperative preparation are prerequisites for successful LVRS. An effective LVRS program requires participation by and communication between experts from pulmonary medicine, thoracic surgery, thoracic anesthesiology, critical care medicine, rehabilitation medicine, respiratory therapy, chest radiology, and nursing. The critical analysis of perioperative outcomes has influenced details of the conduct of the procedure and has established a bilateral, stapled approach as the standard of care for LVRS. The National Emphysema Treatment Trial (NETT) remains the world's largest multi-center, randomized trial comparing LVRS to maximal medical therapy. NETT purposely enrolled a broad spectrum of anatomic patterns of emphysema. This, along with the prospective, audited collection of extensive demographic, physiologic, radiographic, surgical and quality-of-life data, has positioned NETT as the most robust repository of evidence to guide the refinement of patient selection criteria for LVRS, to assist surgeons in providing optimal intraoperative and postoperative care, and to establish benchmarks for survival, complication rates, return to independent living, and durability of response. This article reviews the evolution of current LVRS practice with a particular emphasis on technical aspects of the operation, including the predictors and consequences of its most common complications.

The primary purpose of the National Emphysema Treatment Trial (NETT) was to evaluate the clinical efficacy of lung volume reduction surgery (LVRS) compared with medical therapy as a treatment for advanced emphysema. Transitioning the results of a complex multicenter long-term clinical trial into routine clinical practice is challenging, particularly when the therapy examined is controversial, as was the case in NETT. Aspects of the “clinical art” used by the study investigators to select and treat patients are not always transparent to practitioners reading study publications. At the last NETT Steering Committee meeting, a roundtable discussion was held with investigators, coordinators, Steering Committee leadership, and Data Coordinating Center staff regarding the clinical aspects of patient evaluation and selection and performance of LVRS in advanced emphysema. The questions posed to the meeting participants were ones that are commonly asked by patients and their treating physicians who are considering LVRS and included the following: Why recommend LVRS to a patient? When should LVRS be recommended to a patient? What types of patients are candidates for LVRS? What are the important barriers to performing LVRS? What are the major messages delivered by NETT? It is hoped that answers from NETT investigators to some of these commonly encountered questions will provide clarity and guidance to clinicians faced with the responsibility of considering and discussing LVRS with their patients. NETT investigators were also queried regarding the future directions of research in emphysema and the role that NETT played in shaping that future. The following article is a summary of the highlights of these discussions.

Lung volume reduction surgery (LVRS) is one of a long lineage of surgical approaches to emphysema. The reintroduction of this operation in the mid-1990s led to great controversy over the value of the procedure and its long-term outcomes. The National Emphysema Treatment Trial (NETT) represented an historical scientific collaboration of the National Institutes of Health (NIH), the Centers for Medicare and Medicaid Services (CMS), and the Agency for Health Research and Quality (AHRQ). NETT was designed primarily as a pivotal surgical clinical trial, but also incorporated data collection to inform health policy and cost-benefit analyses. NETT faced challenges that included practical and ethical matters, statistical design and analysis issues, and intense public and political scrutiny. The study design required the development of methods for pulmonary rehabilitation, lung imaging, and exercise testing that have become templates for current clinical and research practice. During the course of the trial, the confidential deliberations of the Data and Safety Monitoring Board (DSMB) played an important role in the ultimate success of the trial and protection of research participants. Because of the importance of the NETT outcomes, the results were disseminated to the medical community and transformed into health policy in a rapid and efficient manner. In many ways, the story of NETT serves as a model for evaluation of new surgical approaches to chronic diseases.

Airflow limitation in COPD patients is not fully reversible. However, there may be large variability in bronchodilator responsiveness (BDR) among COPD patients, and familial aggregation of BDR suggests a genetic component. Therefore we investigated the association between six candidate genes and BDR in subjects with severe COPD. A total of 389 subjects from the National Emphysema Treatment Trial (NETT) were analyzed. Bronchodilator responsiveness to albuterol was expressed in three ways: absolute change in FEV1, change in FEV1 as a percent of baseline FEV1, and change in FEV1 as a percent of predicted FEV1. Genotyping was completed for 122 single nucleotide polymorphisms (SNPs) in six candidate genes (EPHX1, SFTPB, TGFB1, SERPINE2, GSTP1, ADRB2). Associations between BDR phenotypes and SNP genotypes were tested using linear regression, adjusting for age, sex, pack-years of smoking, and height. Genes associated with BDR phenotypes in the NETT subjects were assessed for replication in 127 pedigrees from the Boston Early-Onset COPD (EOCOPD) Study. Three SNPs in EPHX1 (p = 0.009 – 0.04), three SNPs in SERPINE2 (p = 0.004 – 0.05) and two SNPs in ADRB2 (0.04 – 0.05) were significantly associated with BDR phenotypes in NETT subjects. BDR. One SNP in EPHX1 (rs1009668, p = 0.04) was significantly replicated in EOCOPD subjects. SNPs in SFTPB, TGFB1, and GSTP1 genes were not associated with BDR. In conclusion, a polymorphism of EPHX1 was associated with bronchodilator responsiveness phenotypes in subjects with severe COPD.

The principal determining factors influencing the development of the airway disease and emphysema components of COPD have not been clearly defined. Genetic variability in COPD patients might influence the varying degrees of involvement of airway disease and emphysema. Therefore, we investigated genetic association of SNPs in COPD candidate genes for association with emphysema severity and airway wall thickness phenotypes.

Polymorphisms in six candidate genes were analyzed in 379 subjects of the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study with quantitative chest CT data. Genetic association with percent of lung below −950 hounsfield units (LAA950), airway wall thickness (WT), and derived square root wall area of 10 mm internal perimeter airways (SRWA) were investigated.

Three SNPs in EPHX1, five SNPs in SERPINE2, and one SNP in GSTP1 were significantly associated with LAA950. Five SNPs in TGFB1, two SNPs in EPHX1, one SNP in SERPINE2, and two SNPs in ADRB2 were associated with airway wall phenotypes in NETT.

In conclusion, several COPD candidate genes showed evidence for association with airway wall thickness and emphysema severity using CT in a severe COPD population. Further investigation will be required to replicate these genetic associations for emphysema and airway wall phenotypes.

The National Emphysema Treatment Trial (NETT) was a multicenter, randomized, controlled clinical trial, comparing the efficacy of lung volume reduction surgery (LVRS) plus medical management with rehabilitation to medical management with rehabilitation in 1,218 patients with severe emphysema. The NETT was a precedent-setting collaborative effort of three government agencies: the Centers for Medicare and Medicaid Services (CMS); the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH); and the Agency for Healthcare Research and Quality (AHRQ). NETT provided Medicare beneficiaries with controlled access to a promising but unproven procedure, while scientifically valid data on the efficacy and costs were collected to guide future use, coverage decisions, and policy. NETT demonstrates that collaboration among federal agencies and among health plans, researchers, and providers can successfully fulfill their differing missions simultaneously and is a productive approach to evaluating new treatments of mutual interest.

Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS).

Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS.

Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy.

Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information.

Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung.

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients.

Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival.

Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components.

Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.

Conclusions: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease.

Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Background

Hypoxemia, hypercarbia, and pulmonary arterial hypertension are known complications of advanced COPD. We sought to identify genetic polymorphisms associated with these traits in a population of patients with severe COPD from the National Emphysema Treatment Trial (NETT).

Methods

In 389 participants from the NETT Genetics Ancillary Study, single-nucleotide polymorphisms (SNPs) were genotyped in five candidate genes previously associated with COPD susceptibility (EPHX1, SERPINE2, SFTPB, TGFB1, and GSTP1). Linear regression models were used to test for associations among these SNPs and three quantitative COPD-related traits (Pao2, Paco2, and pulmonary artery systolic pressure). Genes associated with hypoxemia were tested for replication in probands from the Boston Early-Onset COPD Study.

Results

In the NETT Genetics Ancillary Study population, SNPs in microsomal epoxide hydrolase (EPHX1) [p = 0.01 to 0.04] and serpin peptidase inhibitor, clade E, member 2 (SERPINE2) [p = 0.04 to 0.008] were associated with hypoxemia. One SNP within surfactant protein B (SFTPB) was associated with pulmonary artery systolic pressure (p = 0.01). In probands from the Boston Early-Onset COPD Study, SNPs in EPHX1 and in SERPINE2 were associated with the requirement for supplemental oxygen.

Conclusions

In participants with severe COPD, SNPs in EPHX1 and SERPINE2 were associated with hypoxemia in two separate study populations, and SNPs from SFTPB were associated with pulmonary artery pressure in the NETT participants.

Background

Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity.

Methods

We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster.

Results

We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470.

Conclusions

Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.

Rationale: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known.

Objectives: To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT).

Methods: A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis.

Measurements and Main Results: There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV1 (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively).

Conclusions: LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.

Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Background: Thoracic gas compression (TGC) exerts a negative effect on forced expiratory flow. Lung resistance, effort during a forced expiratory manoeuvre, and absolute lung volume influence TGC. Lung volume reduction surgery (LVRS) reduces lung resistance and absolute lung volume. LVRS may therefore reduce TGC, and such a reduction might explain in part the improvement in forced expiratory flow with the surgery. A study was conducted to determine the effect of LVRS on TGC and the extent to which reduced TGC contributed to an improvement in forced expiratory volume in 1 second (FEV1) following LVRS.

Methods: The effect of LVRS on TGC was studied using prospectively collected lung mechanics data from 27 subjects with severe emphysema. Several parameters including FEV1, expiratory and inspiratory lung resistance (Rle and Rli), and lung volumes were measured at baseline and 6 months after surgery. Effort during the forced manoeuvre was measured using transpulmonary pressure. A novel method was used to estimate FEV1 corrected for the effect of TGC.

Results: At baseline the FEV1 corrected for gas compression (NFEV1) was significantly higher than FEV1 (p<0.0001). FEV1 increased significantly from baseline (p<0.005) while NFEV1 did not change following surgery (p>0.15). TGC decreased significantly with LVRS (p<0.05). Rle and maximum transpulmonary pressure (TPpeak) during the forced manoeuvre significantly predicted the reduction in TGC following the surgery (Rle: p<0.01; TPpeak: p<0.0001; adjusted R2 = 0.68). The improvement in FEV1 was associated with the reduction in TGC after surgery (p<0.0001, adjusted R2 = 0.58).

Conclusions: LVRS decreased TGC by improving expiratory flow limitation. In turn, the reduction in TGC decreased its negative effect on expiratory flow and therefore explained, in part, the improvement in FEV1 with LVRS in this cohort.

Lung volume reduction surgery (LVRS) has been shown to improve lung function and exercise tolerance in patients with severe emphysema. Some predictors of poor outcome have been described but the role of alpha1-antitrypsin (α1-AT) deficiency is still not well known. The aim of this study was to analyze the results of unilateral LVRS in our center according to the α1-AT status. The results of LVRS in 17 deficient patients and 35 nondeficient patients were analyzed at 3–6 months and 1 year after surgery. Compared with baseline, a significant improvement of FEV1, partial pressure in arterial blood (PaO2), dyspnea score and walking distance was observed in the two groups at 3–6 months after surgery and the studied parameters remained significantly improved at 1 year in the nondeficient group. By contrast, PaO2 and walking distance returned towards baseline in the deficient group at 1 year whereas improvement of FEV1 and dyspnea score was persistent. Mean values of FEV1 at baseline, 3–6 months, and 1 year were 22 ± 6%, 29 ± 11%, and 26 ± 9% and 28 ± 12%, 38 ± 17%, and 40 ± 17% predicted in the deficient group and in the non-deficient group, respectively. In conclusion, the functional benefit is short-lasting in α1-AT deficient patients after unilateral LVRS.

Pulmonary rehabilitation is an established treatment for patients with chronic lung disease. Benefits include improvement in exercise tolerance, symptoms, and quality of life, with a reduction in the use of health care resources. As an adjunct to surgical programs, such as lung volume reduction surgery, pulmonary rehabilitation plays an important role not just in preparing patients for surgery and facilitating recovery but also in selecting patients and ensuring informed choices about treatment options after optimal medical care. In the National Emphysema Treatment Trial (NETT), subjects completed 6–10 weeks of comprehensive pulmonary rehabilitation before randomization and continued rehabilitation throughout the trial, both at home and with intermittent supervision at either an NETT center or an NETT-certified satellite center. Sessions included a combination of upper and lower extremity exercise, education, and psychosocial support. Before randomization, pulmonary rehabilitation resulted in highly significant changes in exercise capacity, dyspnea, and quality of life. As expected, improvements were significantly greater in those without prior rehabilitation experience. Results for patients completing rehabilitation at satellites were similar to those at NETT centers. Prerandomization pulmonary rehabilitation had a significant effect on outcome after lung volume reduction surgery. NETT identified subgroups with differential outcome by treatment (surgical vs. nonsurgical), defined in part by postrehabilitation maximum exercise capacity. Overall, NETT demonstrated the effectiveness of pulmonary rehabilitation in improving function, symptoms, and health status in a large cohort of patients with advanced emphysema treated in a cross-section of programs in the United States.

PURPOSE

This study compared visuomotor speed and cognitive flexibility in emphysema patients treated either with standard multidisciplinary medical therapy (MT) or lung volume reduction surgery (LVRS), followed over a 2-year period.

METHODS

MT patients (n=544) and 542 LVRS patients completed the Trail Making Test (TMT) Parts A and B prior to randomization (baseline). Testing was repeated at 1 and 2 years.

RESULTS

There were no differences on scores for TMT Part A and B between the LVRS and MT groups at baseline or at years 1 and 2. No significant difference between MT and LVRS was noted in terms of overall change in TMT Part A and B over 2 years. The MT group had a significant improvement on TMT-Part A at each followup time compared to baseline (P<.03) but the LVRS group did not. Both the MT and LVRS groups had a significant decline in performance (increase in time to completion) on TMT-Part B when comparing year 1 to baseline (P<.0001).

CONCLUSION

Emphysema patients who received LVRS or MT as treatment performed similarly on measures of visuomotor speed and flexibility at baseline and 1 and 2 year followup. Both groups showed improvement on visuomotor speed during the first year yet overall cognitive flexibility declined. By the second year neither group had any significant change from baseline. These findings suggest that improvement on visuomotor speed and flexibility, observed in a previous 6-month study of LVRS subjects, was not sustained at 1 and 2 year followup.

Delineating the extent and distribution of emphysema is an essential component of the evaluation of candidates for lung volume reduction surgery (LVRS). Imaging also may identify contraindications to LVRS, including bronchiectasis and pleural scarring. The chest X-ray is of limited utility in LVRS evaluation. Chest computed tomography (CT) scanning is an essential component of the evaluation, demonstrating the presence of emphysema and its amount and distribution. Clinical experience has shown that a substantial minority of chest CT scans will also demonstrate pulmonary nodules, some of which represent lung cancers. Published series, including the National Emphysema Treatment Trial, consistently demonstrate that patients with upper lobe predominant or heterogeneous emphysema are most likely to benefit from LVRS. Heterogeneity and distribution can also be assessed by radionuclide ventilation perfusion scanning, but this modality adds little additional information to CT scanning.

It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach.

Purpose: The purpose of this study was to examine the therapeutic effects of lung volume reduction surgery (LVRS) and pulmonary rehabilitation on levels of dyspnea during functional activities in patients with diffuse emphysema. Methods: Fifteen subjects who had undergone LVRS participated in this study. A visual analog scale (VAS) Activity Dyspnea Scales (VADS) measurement tool developed for this study was determined reliable in 10 subjects. The VADS was used to assess changes in dyspnea with functional activity in 10 subjects prior to and following the interventions of LVRS and pulmonary rehabilitation. Results: Results of this study indicate that LVRS followed by pulmonary rehabilitation significantly reduces levels of dyspnea during functional activities. Conclusion: The VADS developed for this study is a valid and reliable method of assessing changes in levels of dyspnea during functional activities in the LVRS population.

BACKGROUND—Lung volume reduction surgery (LVRS) has recently re-emerged as a surgical option for the treatment of end stage chronic obstructive pulmonary disease (COPD) due to underlying severe emphysema. Advocates of LVRS claim that it represents a significant breakthrough in the management of this challenging group of patients while sceptics point to uncertainty about the effectiveness of the operation.
METHODS—A systematic review was conducted of the evidence on the effects of LVRS in patients with end stage COPD secondary to severe emphysema.
RESULTS—The most rigorous evidence on the effectiveness of LVRS came from case series. Seventy five potentially relevant studies were identified and 19 individual series met the methodological criteria for inclusion. The pattern of results was consistent across individual studies despite a significant degree of clinical heterogeneity. Significant short term benefits occurred across a range of outcomes which appeared to continue into the longer term. Physiological improvements were matched by functional and subjective improvements. Early mortality rates were low and late mortality rates compared favourably with those of the general COPD population. However, the entire research base for the intervention is subject to the limitations of study designs without parallel control groups.
CONCLUSIONS—LVRS appears to represent a promising option in the management of patients with severe end stage emphysema. However, until the results of ongoing clinical trials are available, the considerable uncertainty that exists around the effectiveness and cost effectiveness of the procedure will remain.



Lung volume reduction surgery (LVRS) is a costly procedure that can improve quality and quantity of life. Given the prevalence of emphysema, the costs involved with its management, and resource constraints on all health care delivery systems, evaluating the cost-effectiveness of LVRS is important. In this article, we describe the purposes and principles of cost-effectiveness analysis and how those principles were applied in evaluating LVRS. We present the results of the cost-effectiveness analysis that was conducted alongside the National Emphysema Treatment Trial and other economic studies of LVRS and discuss how these should be interpreted in the context of current reimbursement guidelines.

The National Emphysema Treatment Trial (NETT) has published many articles reporting the various outcomes of lung volume reduction surgery versus medical treatment for patients with severe emphysema. However, long and complex clinical trials like NETT that involve both medical and surgical issues generate multiple manuscripts over a period of years and report an array of various outcomes. As a result, the essential findings of the trial may appear to be fragmented to the clinician or clinical researcher or be lost among the many medical reports published each year. In this review, we summarize in one publication the major medical and surgical outcomes of NETT.

Rationale: Previous investigations have identified several potential predictors of outcomes from lung volume reduction surgery (LVRS). A concern regarding these studies has been their small sample size, which may limit generalizability. We therefore sought to examine radiographic and physiologic predictors of surgical outcomes in a large, multicenter clinical investigation, the National Emphysema Treatment Trial.

Objectives: To identify objective radiographic and physiological indices of lung disease that have prognostic value in subjects with chronic obstructive pulmonary disease being evaluated for LVRS.

Methods: A subset of the subjects undergoing LVRS in the National Emphysema Treatment Trial underwent preoperative high-resolution computed tomographic (CT) scanning of the chest and measures of static lung recoil at total lung capacity (SRtlc) and inspiratory resistance (Ri). The relationship between CT measures of emphysema, the ratio of upper to lower zone emphysema, CT measures of airway disease, SRtlc, Ri, the ratio of residual volume to total lung capacity (RV/TLC), and both 6-month postoperative changes in FEV1 and maximal exercise capacity were assessed.

Measurements and Main Results: Physiological measures of lung elastic recoil and inspiratory resistance were not correlated with improvement in either the FEV1 (R = −0.03, P = 0.78 and R = –0.17, P = 0.16, respectively) or maximal exercise capacity (R = –0.02, P = 0.83 and R = 0.08, P = 0.53, respectively). The RV/TLC ratio and CT measures of emphysema and its upper to lower zone ratio were only weakly predictive of postoperative changes in both the FEV1 (R = 0.11, P = 0.01; R = 0.2, P < 0.0001; and R = 0.23, P < 0.0001, respectively) and maximal exercise capacity (R = 0.17, P = 0.0001; R = 0.15, P = 0.002; and R = 0.15, P = 0.002, respectively). CT assessments of airway disease were not predictive of change in FEV1 or exercise capacity in this cohort.

Conclusions: The RV/TLC ratio and CT measures of emphysema and its distribution are weak but statistically significant predictors of outcome after LVRS.