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(Chest. 2005;128:3489-3499.)
© 2005 American College of Chest Physicians

Comparison of Lung Volume Reduction Surgery and Physical Training on Health Status and Physiologic Outcomes*

A Randomized Controlled Clinical Trial

Gunnar Hillerdal, MD, FCCP; Claes-Göran Löfdahl, MD; Kerstin Ström, MD; Bengt-Eric Skoogh, MD; Lennart Jorfeldt, MD; Folke Nilsson, MD; Dycke Forslund-Stiby, PT, MSc; Jonas Ranstam, PhD; Erik Gyllstedt, MD; of the Swedish VOLREM Group

* From the Department of Pulmonary Medicine (Dr. Hillerdal), Karolinska Hospital, Stockholm; Pulmonary Department (Dr. Löfdahl), University Hospital, Lund; Pulmonary Department (Dr. Ström), University Hospital, Umeå; Pulmonary Department (Dr. Skoogh), Sahlgrenska University Hospital, Gothenburg; Department of Pulmonary Physiology (Dr. Jorfeldt), Karolinska Hospital, Stockholm; the Department of Thoracic Surgery (Dr. Nilsson), Sahlgrenska University Hospital, Gothenburg; and Department of Thoracic Surgery (Mr. Forslund-Stiby, Dr. Ranstam, and Dr. Gyllstedt), University Hospital, Lund.

Correspondence to: Gunnar Hillerdal, MD, FCCP, Department of Pulmonary Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden; e-mail: gunnar.hillerdal{at}karolinska.se


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements.

Design: After an initial 6-week physical training program, researchers’ patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year.

Setting: All seven thoracic surgery centers in Sweden.

Patients: All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS.

Interventions: Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively.

Measurements and results: Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV1, residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months.

Conclusions: In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.

Key Words: emphysema • health status • lung function • Medical Outcomes Study Short-Form General Health Survey • St. George Respiratory Questionnaire


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Emphysema is a destructive lung disease causing a decrease in elastic retraction of the lung tissue, compensatory hyperinflation and, in advanced cases, a marked shortness of breath and impaired health status. Even with intense conservative treatment including physical training and other rehabilitative efforts, patients with severe emphysema perceive only small temporary beneficial effects.123

The conservative treatment regimens do not address the problem of diminished elastic recoil in emphysema. In the mid-1990s, lung volume reduction surgery (LVRS), described by Brantigan and Mueller4 in 1957, was reintroduced.5 The point of LVRS is to improve elastic retraction, and this procedure has reportedly achieved clinically significant improvements of lung function, exercise capacity, and quality of health in selected patients.

Until 1996, when this study was conceived, there were no published randomized controlled studies of LVRS. The need for such studies was emphasized in a number of editorials.6789 Therefore, all centers in Sweden performing thoracic surgery agreed to participate in a prospective randomized controlled trial comparing LVRS including an exercise training program with a training program alone. This meant that all patients considered for LVRS in Sweden, which has approximately 9 million inhabitants, were evaluated for the study. The aim of the present study is to compare LVRS and continued physical training with physical training alone for 1 year using measurement of health status as the primary end point. Since the start of this trial, a number of controlled studies have been published including the large US National Emphysema Treatment Trial (NETT).1011121314


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Design
Initially, all patients enrolled in the study participated in an intense physical training program for a minimum of 6 weeks. This was based on our own clinical experience that preoperative exercise training considerably reduces perioperative complications and mortality, which is also supported by published data from other groups.1011131415 Patients who failed to comply with the training program were excluded. After the initial training program, patients were randomized to either LVRS (surgical group [SG]) or to continued physical training (training group [TG]), provided they were still eligible according to the criteria, including willingness to participate. The SG also continued the training after surgery for 3 months, following the same regimen. Both groups were followed up for 1 year postoperatively or after randomization. After this, patients in the TG who still fulfilled the criteria were offered LVRS (Table 1 ). If a patient in the TG deteriorated very rapidly, the protocol allowed for "rescue LVRS." This paragraph was added at the request of the Ethics Committee. Symptomatic treatment with bronchodilators, inhaled steroids, and other drugs prescribed by physicians were allowed and continued during the study.


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  		Table 1.. Inclusion and Exclusion Criteria

 
Patient Enrollment and Randomization Procedure
All patients considered for LVRS in Sweden between March 1997 and March 2000 were evaluated for the study. Patients with severe emphysema were initially evaluated by pulmonologists. Potential candidates for LVRS were referred to the emphysema panel at one of the seven operating centers. These panels consisted of thoracic surgeons, pulmonologists, radiologists, clinical physiologists, and physical therapists. If LVRS was considered an option, the patients underwent a complete evaluation; if fulfilling inclusion criteria and having none of the exclusion criteria (Table 1), the patients were preliminarily accepted for the study. In each case, the panel assessed the criterion "locally worse areas" with the aid of CT scan and pulmonary scintigraphy.

A total of 304 patients were initially considered for LVRS (Fig 1 ). One hundred ninety patients were then excluded because they did not fulfill all inclusion criteria. Of these, 72 patients (38%) had emphysema that was technically inoperable or homogenous, 62 patients (33%) were in too poor general condition or were found to have other diseases (heart disease, bronchiectasis, significant reversibility), and 19 patients (10%) refused to participate after evaluation. Three patients were unable to fulfill the training program, and five patients died before starting training or during the period of prerandomization training, one from suicide. Thus, in all, 106 patients (50 patients, 31 patients, and 25 patients per year) were randomized, 53 to each group. No patients were unavailable for follow-up.



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  		Figure 1.. Patient flow.

 
Randomization was done according to separate lists, randomized for each center in blocks of four patients. The lists were kept at the study computer center. All randomization was strictly consecutive, and the randomization procedure (including the size of the blocks) was concealed from the participants.

Physical Training and Surgical Procedures
Physical training was done in small groups, according to a detailed protocol, at biweekly sessions led by a certified physical therapist and supplemented by a program of home exercise at least three times weekly. The groups included from one to five patients, depending on the number of patients enrolled in each center at that point in time. All patients exercised on a bicycle ergometer at a workload of 60 to 70% of their maximal exercise capacity3 and performed muscle strength training exercises. Oxygen supplementation was used during training if saturation fell to < 90%, with the purpose of maintaining oxygen saturation at ≥ 95%. The home training program involved muscle training and individualized instructions to achieve a similar workload. The supervised training continued for 3 months postoperatively in the SG and for a full year in the TG; we strongly recommended that SG patients continue their home exercise program.

Bilateral LVRS was performed by median sternotomy, as described by Cooper et al,5 in 42 patients and by video-assisted thoracoscopy in 3 patients, depending on local custom and experience. In four patients, in whom a gross difference between the left and right sides with an obvious unilateral target area was seen, unilateral LVRS was performed via thoracotomy. The most emphysematous areas targeted by chest CT scanning and ventilation/perfusion scanning were excised using various mechanical staplers. In order to minimize air leaks, staple lines were reinforced with bovine pericardial tissue or a substitute. At surgery, the excised lung volume was visually estimated by the thoracic surgeon to be approximately 20 to 30% of the total.

Measurements
Health status was measured after 6 weeks of exercise training, prior to randomization, and at 6 months and 12 months, using validated Swedish versions of the generic 36-item Medical Outcomes Study Short-Form General Health Survey (SF-36),16 with scores ranging from 0 (poor health status) to 100 (good health status) and the disease-specific St. George Respiratory Questionnaire (SGRQ),1718 with scores ranging from 0 (good health status) to 100 (poor health status). Both questionnaires are self-administered, and the scores were calculated according to the methods described in their respective manuals, which include how to deal with individual missing questionnaire items (partially missing information is imputed using the last observation carried forward principle). The SGRQ consists of 50 items forming three component scales: symptoms, activity, and impacts, as well as a total score including all items. The SF-36 includes eight scales: physical function, physical role limitation, pain, personal perceptions of health, vitality, social function, emotional role limitation, and mental health. For both questionnaires, the minimal important clinical difference was defined as a score of 4 scale points. The questionnaires were checked to ensure that all questions were answered before the patients left the clinic.

All functional tests were performed prior to randomization. Standard tests, such as measurements of static and dynamic volumes before and after bronchodilatation (FEV1, FVC, and vital capacity [VC]) as well as the incremental shuttle walking test19 were also performed 3 months, 6 months, 9 months, and 12 months after surgery (SG) or randomization (TG). No more than a 3-week difference from the optimal date was allowed.

Tests were standardized at all centers. Static volumes (total lung capacity [TLC], residual volume [RV], and functional residual capacity) were determined using a body plethysmograph and a near-maximal, incremental, symptom-limited bicycle exercise test (initial workload of 10 W with 10-W increments every minute)20 was carried out after 6 months and 12 months. Diffusion capacity of the lung for carbon monoxide (DLCO) was measured at baseline and after 12 months. Postbronchodilator FEV1 and VC and prebronchodilator static volumes and DLCO were used in all analyses and tables. We used the Coal and Steel Union tables21 for normal values.

In the shuttle walking test, the patients walk 10 m at a set speed; after each 10 m, the speed was increased in a standardized manner. The total distance walked was reported.19 The test was performed by licensed physical therapists who met before the study began in order to learn the method and subsequently met several times during the study in order to ensure that the method was standardized nationwide.

Data Evaluation and Statistics
The primary end point was health status measurement; secondary end points included survival, exercise capacity, and pulmonary function test findings. Patient number calculations showed that 45 patients in each group would be sufficient to assess an effect size (ie, difference relative to the SD) of 60% in relation to health status between groups, as measured using the total SGRQ scale after 12 months with a statistical power of 80%, 5% statistical significance, and two-sided tests. Questionnaires and other data were sent to the computer center, where secretaries who were unaware of the patients’ surgical status processed and fed the data into the computer.

We tested differences between groups with reference to changes from baseline in SGRQ scores, SF-36 scores, shuttle walking test results, maximal exercise capacity, and lung function variables using the Student t test. Changes from baseline within groups were tested using the paired t test. We based the power calculations on two-sided tests. Confidence intervals (CIs) for the means were calculated using the t distribution, and adjustments for differences in baseline characteristics (age, sex, shuttle walking test, maximal exercise capacity, lung function variables, and {alpha}1-antitrypsin deficiency) were done using analysis of covariance (ANCOVA) with treatment as a fixed effect and age and sex as covariates. The analysis was done on an intention-to-treat basis.

We compared mortality rates 1 year after randomization of the two groups using Kaplan-Meier analysis (log-rank test). All reported p values are for two-sided tests. The level of significance was set at 5%, and the confidence level was 95%. We used the statistical software (SPSS; Chicago, IL) to perform the statistical analysis.

Ethics and Safety
All patients were informed orally and in writing, and gave their oral consent. All seven medical ethics committees in Sweden, one at each regional hospital, approved the trial. A safety committee consisting of two independent experts reviewed the hospital records of deceased patients to suggest measures regarding patient safety.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Baseline Data, Withdrawals, and Rescue LVRS
Forty-five men and 61 women with a mean age of 62 years were randomized to the study. Their mean FEV1 and RV were 26% and 261% of predicted, respectively. The SG included 27 men and 26 women, and the TG included 18 men and 35 women, the difference being nonsignificant (two-sided Fisher Exact Test). Fourteen patients, 8 of whom underwent surgery, had homozygous {alpha}1-antitrypsin deficiency.

After the safety committee reviewed the data of the first five patients who died after surgery, a DLCO of ≤ 20% of predicted was added as an exclusion criterion. Before this, eight patients in the SG and two patients in the TG with levels at or below this were included in the study.

For logistical reasons, there was a waiting period of up to 6 weeks from the time of randomization until surgery actually took place. During this waiting period, four patients in the SG were withdrawn before surgery (three patients deteriorated, one of whom underwent transplantation, and one patient no longer wished to undergo surgery); therefore, LVRS was performed on 49 of the 53 patients randomized to surgery. In the TG, two patients withdrew their consent, two patients deteriorated and were unable to participate in the training program, and two patients acquired other diseases (heart disease and pulmonary fibrosis, respectively) [Fig 1].

Two patients in the TG underwent surgery during the follow-up period (114 days and 250 days after randomization, respectively) because of rapid deterioration ("rescue LVRS" according to the protocol). Since the analysis was based on intention to treat, these patients were included according to the original randomized group assignment.

The patients attended all supervised training sessions and stayed home only when they had an infection. All patients kept a diary describing their participation and compliance with the home training program; as far as can be judged, compliance was good. There was no noticeable difference between the TG and the SG in these aspects.

Health Status
In the SG, health status as measured by all SGRQ scales at 6 months and 12 months was improved. In the TG, the activity component deteriorated by 8 points, but otherwise there were no changes over time (Table 2 ). The differences between the two groups regarding changes from baseline at 6 months and 12 months were significant in most component scales (Table 3 ). In the SG, 32 patients improved ≥ 4 U at 6 months and 26 patients improved ≥ 4 U at 12 months. In the TG, 12 patients improved ≥ 4 U at 6 months and 10 patients improved ≥ 4 U at 12 months. Age, sex, and baseline characteristics, including differences in {alpha}1-antitrypsin levels, were not related to changes in SGRQ score. However, among operated patients, there appeared to be a negative linear relationship between baseline SGRQ total score and changes in SGRQ total score at 6 months and 12 months (p < 0.05). In other words, patients with the worst baseline scores improved the most. There was improvement in the SF-36 physical function, physical role limitation, and vitality at 6 months, and physical function, physical role limitation, personal perception of health, social function, and mental health at 12 months in the SG but not in the TG (Table 3).


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  		Table 2.. Health Status (SGRQ and SF-36) at Baseline and at 6 Months and 12 Months After Surgery*

 

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  		Table 3.. Age- and Sex-Adjusted Differences in Change of Health Status (SGRQ and SF-36) Between the SG and the TG at Baseline and Change in Quality of Life During the First 6 Months and the First 12 Months After Surgery or Randomization Using Intention-to-Treat Analysis With Replacement of Censored Observations According to Last-Observed Value Carried Forward*

 
Lung Function and Exercise Capacity
RV and TLC decreased in the SG but remained essentially unchanged in the TG (Table 4 ). No significant change in DLCO occurred in either group after 1 year. FEV1, VC, RV, and TLC demonstrated differences between the two groups both after 6 months (not RV) and 12 months with respect to changes from baseline (Table 5 , Fig 2 ). In the SG, there was improvement (p < 0.001 for FEV1 at both 6 months and 12 months), while in the TG the variables tended to decrease.


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  		Table 4.. Lung Function and Exercise Capacity at Baseline and at 6 Months and 12 Months After Surgery or Randomization for the SG and the TG*

 

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  		Table 5.. Age- and Sex-Adjusted Differences in Lung Function and Exercise Capacity Between the SG and the TG at Baseline and at 6 Months and 12 Months After Surgery or Randomization*

 


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  		Figure 2.. Absolute change (mean values and SD) as a percentage of predicted normal FEV1 from baseline in patients randomized to volume reduction surgery (SG) and to continued training (TG).

 
Shuttle walking test and exercise capacity demonstrated differences concerning changes from baseline (Table 5, Fig 3 ) between the two groups after 6 months and 12 months. Both variables improved in the SG, slightly more at 6 months than at 12 months. In the TG, we observed a tendency toward decreasing values.



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  		Figure 3.. Change in meters in shuttle walking test (SWT) [mean values and SD] from baseline in patients randomized to volume reduction surgery (SG) and to continued training (TG).

 
Mortality
There were seven deaths in the SG (13%) and two deaths in the TG (4%) [Fig 4 ]. This difference was not statistically significant (Kaplan-Meier analysis, p = 0.489). Six in-hospital deaths occurred after surgery (12%) caused by pneumonia and respiratory failure (on days 9, 15, 19, 42, 49, and 71). One surgically treated patient died suddenly at home 107 days after surgery. Respiratory failure was the cause of the two deaths in the TG (on days 178 and 215 after randomization).



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  		Figure 4.. Kaplan-Meier curve of actual mortality in patients randomized to volume reduction surgery (SG) and to continued training (TG).

 
Five patients in the SG group had a postbronchodilator FEV1 of ≤ 20% of the predicted value, and two of them died postoperatively. These two patients also had a DLCO of ≤ 20% of predicted value. SGRQ was measured at baseline in five of the six patients inpatients who died postoperatively and their SGRQ activity scores were significantly worse than that in patients surviving surgery (p < 0.001) [Table 6 ]. At the four centers with < 10 patients enrolled, there were two inpatient fatalities in 11 operated patients (18% mortality), whereas inpatient mortality was 11% at the other three centers. After considering DLCO and SGRQ activity score, there was no difference in postoperative mortality related to center size.


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  		Table 6.. Baseline Data for Patients Who Died During the Observation Year and Those Receiving Rescue LVRS. Within brackets, days after surgery or randomization, respectively*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study shows that improvements, not only in exercise capacity and lung function, but particularly in health status as measured by both a disease-specific and a general health questionnaire, can be obtained through LVRS in selected patients, compared with patients who only undergo physical training. The improvements are similar to those obtained in other studies,101112131415222324 both randomized and nonrandomized. These gains are, however, achieved at a cost: a considerable risk of mortality.

This study has limitations. For instance, not all of the 106 randomized patients contributed baseline information to all end points; at follow-up, information was missing for some of the patients as well. This is the reason we used the last-observed value carried forward technique. However, unless data missing from the two groups relate differently to outcome, this does not bias the results. We believe that our results display true effects of treatment, not selection.

Furthermore, the primary end point, health status measurement, is based on two assessments using questionnaires (SGRQ and SF-36), and both rely on assessment of subscores. This could create multiplicity problems in terms of statistical significance. Again, we do not believe this is a major issue because the overall outcome from both questionnaires is that the two groups show statistically significant treatment effects.

Compared with the NETT,13 the baseline SGRQ score of our patients was worse (total scores approximately 59 and 53, respectively). The baseline results of SF-36 also reflected severe impairment, especially in physical domain, as well as in general health and vitality. Moreover, although FEV1 was almost identical (26% or 27% of predicted in our study and 27% in the NETT), RV was 261% of predicted in our study and 222% in the NETT. In contrast, maximal workload capacity at randomization was considerably higher in our patients: 56 W and 51 W for SG and TG, respectively, compared with 39 for both groups in the NETT. This might possibly be related to the fact that the mean age of patients in our study was 62 years compared with 67 years in the NETT. These findings raise some intriguing questions about national differences in the subjective evaluation of health and how results from different countries should be compared.

The improvement of health status in operated patients was obvious, both in baseline measurements and in comparison with the group receiving physical training alone. The disease-specific SGRQ questionnaire has an empirically derived definition of clinically significant change in scores, 4 U being the minimal significant difference.25 Most interventions, such as physical training and pharmacologic treatment, in patients with COPD have demonstrated effects in the vicinity of this minimally important difference. The improvement obtained by LVRS compared with training alone in the present study was more pronounced, with a total score gain of – 14.7.

The generic health status questionnaire score (SF-36) also showed improvement after surgery compared with training alone. Improvement was most pronounced in physical measurements such as physical function, but also in domains such as social function and mental health, which showed significantly more improvement after LVRS than after physical training alone. The physical function domain is most closely related to the SGRQ measurement, and probably also reflects the improvement seen in these patients within work capacity measurements, such as the shuttle walking test. SF-36 has previously been used in other studies1123 of LVRS, as in our own study, which also showed improvement following surgery. In one of these studies,11 only one measure is presented, but which one is not clear. Another study23 showed changes in the same domains as seen in the patients in our study. In general, the generic questionnaires are insensitive to interventions in COPD.123 The improvement observed 6 months and 12 months after LVRS is therefore exceptional for a COPD intervention.

It could be argued that the operation per se has a strong placebo effect in patients who are expecting improvement, and that this could explain the improved health status. Our trial design does not exclude that possibility. However, the magnitude of the effect in both SF-36 and in SGRQ speaks against this explanation. Further, the duration of improvement 1 year after surgery is in our view also an argument against this explanation, as is the fact that the improvement in HQRL closely parallels improvement in function.

After an initial improvement in health status among operated patients, a slight deterioration seems to occur between 6 months and 12 months. This is consistent with observations made in other studies.11131415 In addition, it fits well with the general concept that COPD is a slowly progressive disease even with regard to HRQL measurements.26

Some of the criteria for LVRS, such as "locally worse areas," are by necessity arbitrary at this time. Experience among members of the panel is the most important factor in evaluating this, and consequently it is possible that patient selection is somewhat different in various studies. Until we can reach consensus on more precise criteria, we have to accept this. It should be pointed out that the criteria used for most groups are similar.

In the TG, both lung function tests and health status had a tendency to deteriorate after randomization, despite intense rehabilitation. This is in contrast to the findings of other studies123 on rehabilitation procedures in COPD, in which health status improved. However, the patients in these earlier studies had a better functional status initially than the patients in the present study. It is also possible that in our study improvement was already achieved during the prerandomization period, when no measurement of health status was done. In fact, many studies3 of the effects of training have been made for the comparatively short period of just 6 to 8 weeks, which was enough time to show improvement. In the randomized studies10111314 of LVRS vs training alone that have been published to date, most include a prerandomization exercise training period of at least 6 weeks. In these studies,10111314 as in ours, there was no additional improvement at 6 months or 12 months in the training group.

There was concern over the relatively high inpatient postsurgical mortality in the early phases of this study. Therefore, the safety committee reviewed the data and patient records. This led to the recommendation that patients with a DLCO < 20% of predicted should not be included. After the addition of this exclusion criterion, only one more inpatient fatality case was seen in the study. A very similar finding, with almost identical changes to the inclusion criteria during an ongoing study, was reported both in the NETT study1327 and in the study by Geddes et al.11

It is clear that in this trial, those patients who died in the hospital following surgery had more severe disease as a group than the others (Table 6). Their baseline lung function parameters, including FEV1 and DLCO, were worse and their health status was more severely deteriorated. In patients with an activity domain of SGRQ score of ≥ 93, mortality was 5 of 14 cases (36%), whereas no deaths were seen in patients in whom the score was < 93 (33 cases).

In previous reports,1115 there has been a wide variation in surgical deaths: the 90-day mortality rate has varied from 3 to 17%. In a meta-analysis22 of uncontrolled studies, median mortality was 7%. A controlled study11 from the United Kingdom showed an inpatient mortality rate of 17%, and the NETT27 reported a 30-day mortality rate of 16% in patients with FEV1 < 20% of predicted, but an overall mortality in the "other" group (ie, where high-risk patients were excluded) of 5.2%. These data are consistent with ours. Thus, careful evaluation and selection of patients is mandatory to achieve acceptable results from LVRS.

In conclusion, LVRS can now be regarded as an established form of treatment for diffuse but nonheterogeneous emphysema in selected patients, albeit at the risk of surgical mortality. The effects seem to be stable for at least a year, and no other method (with the exception of lung transplantation) can give such a large increase in health-related quality of life. Surgical mortality is increased in patients with highly limited physical activity (SGRQ activity score of ≤ 93%) and in patients with poor lung function, especially with DLCO < 20%.


   Acknowledgements
 
We thank the members of the Swedish VOLREM Group: Marianne Alton, Regional Hospital, Örebro; Per Jakobsson, University Hospital, Linköping; Per-Arne Kling, Blekinge Hospital, Karlskrona; Rune Lundgren, University Hospital, Umeå; Otto Nettelbladt, Academic Hospital, Uppsala; and Lotta Orre, MD, Karolinska Hospital, Stockholm. We are grateful to all staff at the various centers in Sweden from which patients were referred and where they were followed and treated after surgery at the regional hospitals. We are also grateful for the expertise and work by Professors Jacob Boe, Oslo, Norway, and Bo Simonsson, Lund, Sweden, in performing the safety evaluation.


   Footnotes
 
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; DLCO = diffusion capacity of the lung for carbon monoxide; LVRS = lung volume reduction surgery; NETT = National Emphysema Treatment Trial; SF-36 = Medical Outcomes Study Short-Form General Health Survey; SG = surgical group; SGRQ = St. George Respiratory Questionnaire; TG = training group; TLC = total lung capacity; VC = vital capacity

Supported by a generous grant from the Swedish Heart-Lung Foundation.

Received for publication January 5, 2004. Accepted for publication June 27, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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