Volume 133, Issue 6 , Pages 1434-1438, June 2007
Lung-volume reduction surgery for pulmonary emphysema: Improvement in body mass index, airflow obstruction, dyspnea, and exercise capacity index after 1 year
Article Outline
Objectives
We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index.
Methods
In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient.
Results
Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P < .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year.
Conclusion
Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.
CTSNet classification: 11
Abbreviations and Acronyms: BODE, body mass index, airflow obstruction, dyspnea, and exercise capacity, COPD, chronic obstructive pulmonary disease, FEV1, forced expiratory volume in 1 second, IQR, interquartile range, LVRS, lung-volume reduction surgery, NETT, National Emphysema Treatment Trial
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, affecting 24 million Americans and accounting for 119,000 deaths in the year 2000.1 Affected patients suffer from dyspnea, functional impairment, recurrent bronchopulmonary infections, and respiratory failure. Although inhaled corticosteroids, long-acting bronchodilators, and pulmonary rehabilitation improve some outcomes of this disease, only long-term oxygen therapy and lung-volume reduction surgery (LVRS) have been shown to improve survival in selected patients with COPD.2, 3, 4
See related editorial on page 1412.
The National Emphysema Treatment Trial (NETT) showed that patients with both low postrehabilitation exercise capacity and predominantly upper-lobe pulmonary emphysema had improved survival, exercise capacity, and quality of life with LVRS relative to those who did not undergo surgery.4 A total of 1218 study subjects was used to detect these between-group differences.
The identification of a clinically meaningful surrogate end point that predicts survival for patients with COPD and is affected by therapeutic interventions offers the potential for designing appropriately powered clinical trials with a fraction of the time and resources required by trials such as NETT. The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index is such a potential surrogate end point in COPD.5 This multidimensional measure is composed of forced expiratory volume in 1 second (FEV1), the 6-minute walk distance, the modified Medical Research Council dyspnea score, and body mass index (Table 1). The BODE index is calculated by summing scores assigned to each of its four components, resulting in an overall score from 0 to 10; higher scores signify more severe disease. In a multinational cohort study, each 1-point increment in the BODE index conferred a 34% increased risk of death from all causes and a 62% increased risk of respiratory-related death.5 The BODE index was a better predictor of mortality than was FEV1 alone.
TABLE 1. Components of body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index
| Points on BODE index | ||||
|---|---|---|---|---|
| Variable | 0 | 1 | 2 | 3 |
| Forced expiratory volume in 1 s (% predicted) | ≥65 | 50–64 | 36–49 | ≤35 |
| 6-min walk distance (m) | ≥350 | 250–349 | 150–249 | ≤149 |
| Modified Medical Research Council dyspnea score⁎ | 0-1 | 2 | 3 | 4 |
| Body mass index (kg/m2) | >21 | ≤21 | ||
⁎The modified Medical Research Council dyspnea scale can range from 0 to 4, with a score of 4 indicating that the patient is too breathless to leave the house or becomes breathless when dressing or undressing. (Adapted with permission from Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:1005-12. Copyright © 2004 Massachusetts Medical Society. All rights reserved) |
In this study of patients undergoing LVRS after closure of NETT, we hypothesized that LVRS would improve the BODE index 1 year after surgery. We also explored preoperative predictors of improvement in the BODE index 1 year after surgery. These results have been published previously in abstract form.6, 7
Materials and Methods
We performed a prospective cohort study of patients undergoing LVRS at Columbia University Medical Center between January 2004 and August 2005. The Columbia University Medical Center institutional review board approved the study.
Patients were evaluated for LVRS by our multidisciplinary team with the methodology and selection criteria of NETT (Table 2).8 Postbronchodilator spirometry, plethysmography, single-breath carbon monoxide diffusing capacity, room air arterial blood gas analysis, 6-minute walk testing, and cardiopulmonary exercise testing were performed as previously described.4 All exercise testing was performed after pulmonary rehabilitation. The BODE index was calculated as described by Celli and colleauges5 (Table 1).
TABLE 2. Inclusion and exclusion criteria
| Inclusion criteria |
 History and physical examination consistent with pulmonary emphysema |
| Body mass index ≤31.1 kg/m2 for men or ≤32.3 kg/m2 for women |
| Prednisone dose ≤20 mg/d |
| Evidence of pulmonary emphysema on high-resolution computed tomographic scan |
| Forced expiratory volume in 1 s ≤45% predicted (and ≥15% for those >70 years old) |
| Total lung capacity ≥100% predicted, residual volume ≥150% predicted |
| Paco2 ≤60 mm Hg |
| Pao2 ≥45 mm Hg breathing room air |
| Completion of pulmonary rehabilitation |
| After rehabilitation, 6-min walk distance ≥140 m |
| Exclusion criteria |
| Current use of tobacco |
| Previous lung-volume reduction surgery, lung transplantation, or lobectomy |
| Clinically significant cardiac disease |
| Recurrent pulmonary infections |
| Pleural or interstitial lung disease |
| Systolic pulmonary artery pressure ≥45 mm Hg |
| Requirement for >6 L oxygen to maintain oxygen saturation ≥90% with exercise |
| Diffuse emphysema unsuitable for lung volume reduction surgery |
After pulmonary rehabilitation, patients who met all inclusion criteria and no exclusion criteria underwent LVRS. Surgical technique was either bilateral video-assisted thoracoscopic surgery or median sternotomy with the use of buttressed staple lines for resection. Patients underwent postoperative inpatient or outpatient rehabilitation as clinically indicated. One year after surgery, patients returned for repeated testing.
We confirmed deaths with the Social Security Death Index. Incomplete follow-up after LVRS, however, is likely due to worsened health status or death.9 We therefore imputed missing 1-year data with the worst 1-year values in the entire cohort (worst rank score imputation).10 For example, missing FEV1 values were replaced with the lowest FEV1 in the cohort (20%), whereas missing BODE index values were replaced with the highest BODE index in the cohort (6). This conservative approach was intended to minimize any effect of LVRS on these end points.
Statistical Analysis
Continuous variables were summarized by mean ± SD. Discrete ordinal variables were summarized by median, range, and interquartile range (IQR). Categorical variables were summarized by frequency and percentage. The Wilcoxon signed rank test was used to compare changes in continuous and ordinal discrete variables. The Spearman correlation coefficient was used to identify preoperative variables that were associated with the percentage reduction (improvement) in BODE index from baseline to 1-year follow-up.
Results
Twenty-three patients underwent LVRS during the study period (Table 3). The average age was 62 ± 6 years, and 65% were female. More than 90% received inhaled corticosteroids and long-acting β2-agonists, 48% used tiotropium, and 57% used long-term oxygen therapy. The median modified Medical Research Council dyspnea score was 3 (IQR 2-3). The average forced vital capacity was 59% ± 13% predicted, and the average FEV1 was 25% ± 5% predicted. All 23 patients had predominantly upper-lobe pulmonary emphysema, as demonstrated by computed tomography. Seven (30%) had low postrehabilitation exercise capacity as defined by NETT (maximal workload during cardiopulmonary exercise testing <25 W for women or <40 Watts for men), and 16 (70%) had high exercise capacity.
TABLE 3. Baseline characteristics
| Variable | |
|---|---|
| No. of patients | 23 |
| Age (y, mean ± SD) | 62±6 |
| Female (No.) | 15(65%) |
| Body mass index (kg/m2, mean ± SD) | 26±4 |
| Predominantly upper-lobe emphysema (No.) | 23(100%) |
| Resting pulmonary function | |
| FVC (% predicted, mean ± SD) | 59%±13% |
| FEV1 (% predicted, mean ± SD) | 25%±5% |
| FEV1/FVC ratio (%, mean ± SD) | 35%±8% |
| Residual volume (% predicted, mean ± SD) | 222%±45% |
| Diffusing capacity of carbon monoxide (% predicted, mean ± SD) | 25%±8% |
| Paco2 (mm Hg, mean ± SD) | 43±3 |
| Pao2 on room air (mm Hg, mean ± SD) | 66±10 |
| Exercise capacity | |
| Maximal workload (W, mean ± SD) | |
| Female (n = 15) | 34±10 |
| Male (n=8) | 46±16 |
| Low exercise capacity (No.) | 7(30%) |
| High exercise capacity (No.) | 16(70%) |
| Distance for 6-min walk (m, mean ± SD) | 417±73 |
Surgical outcomes are presented in Table 4. Fourteen patients (61%) underwent LVRS through bilateral video-assisted thoracoscopic surgery, and 9 (39%) by median sternotomy. All patients were extubated in the operating room. The median intensive care unit stay was 2 days (range 1-7 days), and the median hospital stay was 8 days (range 5-18 days). Nine patients (39%) had a prolonged air leak (>7 days), and there was 1 episode each of pneumonia, infected pleural space, arrhythmia, and transfusion of more than 2 units of packed red blood cells. There were no deaths, reintubations, or episodes of extended mechanical ventilation.
TABLE 4. Surgical outcomes
| Variable | |
|---|---|
| Hospital stay (d, median and range) | 8(5–18) |
| Intensive care unit stay (d, median and range) | 2(1–7) |
| Deaths (No.) | 0 |
| Complications (No.) | |
| Prolonged air leak (>7 days) | 9(39) |
| Pneumonia | 1(4) |
| Infected pleural space | 1(4) |
| Arrhythmia | 1(4) |
| Transfusion >2 units | 1(4) |
To date, 20 patients have completed 1-year follow-up and 3 have not. None of the 23 patients in the cohort underwent lung transplantation or died during follow-up. There were clinically significant improvements in forced vital capacity, FEV1, total lung capacity, single-breath carbon monoxide diffusing capacity, and Pao2 on room air (Table 5). Exercise capacity also improved, as measured by maximal workload during cardiopulmonary exercise testing and the 6-minute walk distance. Improved exercise capacity was accompanied by an improvement in peak minute ventilation. Exertional dyspnea, but not exertional fatigue, improved as well.
TABLE 5. One year outcomes after lung-volume reduction surgery
| Variable | Baseline (n = 23) | At 1 y (n = 23) | P value |
|---|---|---|---|
| Resting pulmonary function | |||
| Forced vital capacity (% predicted, mean ± SD) | 59±13 | 71±16 | .0007 |
| Forced expiratory volume in 1 s (% predicted, mean ± SD) | 25±5 | 33±11 | <.0001 |
| Total lung capacity (% predicted, mean ± SD) | 121±13 | 116±22 | .04 |
| Diffusing capacity of carbon monoxide (% predicted, mean ± SD) | 25±8 | 31±9 | <.0001 |
| Pao2 on room air (mm Hg, mean ± SD) | 66±10 | 70±9 | .049 |
| Cardiopulmonary exercise testing | |||
| Maximal workload (W, mean ± SD) | 39±14 | 45±18 | .02 |
| Maximum oxygen volume (mL/[min · kg], mean ± SD) | 12.0±2.5 | 12.6±3.6 | .48 |
| Peak minute ventilation, body temperature and pressure, saturated (L/min, mean ± SD) | 24±7 | 28±9 | .01 |
| Test of 6-min walk | |||
| Walk distance (m, mean ± SD) | 417±73 | 455±71 | .001 |
| Borg dyspnea score (median and interquartile range) | 4(4–5) | 3(1–4) | .003 |
| Borg fatigue score (median and interquartile range) | 3(1–4) | 3(0–4) | .77 |
| Modified Medical Research Council dyspnea score (median and interquartile range) | 3(2–3) | 1(0–2) | <.0001 |
| BODE index scores (median and interquartile range) | |||
| Total BODE index | 5(4–5) | 3(2–4) | <.0001 |
| Forced expiratory volume in 1 s BODE score | 3(3–3) | 3(2–3) | .002 |
| Walk distance BODE score | 0(0–0) | 0(0–0) | >.9999 |
| Modified Medical Research Council dyspnea BODE score | 2(1–2) | 0(0–1) | <.0001 |
| Body mass index BODE score | 0(0–0) | 0(0–1) | >.9999 |
The BODE index improved from a median of 5 (IQR 4-5) before surgery to a median of 3 (IQR 2-4) 1 year after surgery (P < .0001). Of the four BODE index components, only the FEV1 and dyspnea scores changed during the study period (Table 5).
Among the 20 patients with 1-year follow-up, preoperative 6-minute walk distance (r = −0.48, P = .03) and postwalk Borg fatigue score (r = −0.65, P = .002) were each inversely associated with improvement in the BODE index after 1 year.
Discussion
LVRS improved the BODE index 1 year after surgery in this post-NETT prospective study of patients with predominantly upper-lobe pulmonary emphysema. Complications were minimal, and there were no deaths. Furthermore, lower preoperative 6-minute walk distance and lower Borg fatigue scores after walk testing were each associated with greater improvements in the BODE index after 1 year.
We found improvements in the BODE index in 17 of 23 patients after 1 year. Our results build on previous reports of improvements in the BODE index 3 months after LVRS and after pulmonary rehabilitation.11, 12 Imfeld and coworkers11 found that improvement in the BODE index 3 months after LVRS was associated with lower subsequent mortality. Although encouraging, however, these data do not establish the BODE index as a validated surrogate end point, because no randomized trial has yet examined the BODE index. Future studies are needed to examine this issue.
Although we found meaningful improvements in both 6-minute walk distance and maximal workload during cardiopulmonary exercise testing, we did not detect a change in the 6-minute walk distance component of the BODE index. Our high mean baseline 6-minute walk distance (417 m) is well above the threshold value of 350 m below which the BODE index increases (Table 1). In fact, only 2 patients had a baseline 6-minute walk distance less than 350 m (each had a walk distance BODE score of 1), leaving little room for improvement.
Despite the insensitivity of the BODE index to improvements in 6-minute walk distance in our study, we identified lower preoperative 6-minute walk distance as a predictor of the magnitude of improvement in the BODE index after 1 year. This finding fits well with the current paradigm that LVRS confers the greatest benefit to those with the lowest exercise capacity.4 In addition, those patients who reported greater degrees of fatigue after 6-minute walk testing had smaller improvements in the BODE index. One interpretation of this finding is that LVRS benefits those whose exercise is limited by dyspnea (suggesting limitation by lung disease) rather than fatigue (which would suggest limitation by deconditioning or cardiac disease).
After the closure of NETT, we continued to use NETT selection criteria and protocols in our institutional approach to LVRS. We credit our early success to the strict patient selection of NETT and the efforts of our multidisciplinary LVRS team, which is composed of thoracic surgeons, pulmonologists, thoracic radiologists, a physiatrist, nurses, and physical and respiratory therapists.
There are several limitations to our study. First, our sample size was small. We suggest that our predictors of BODE improvement should be confirmed in a larger study. Second, as emphasized previously, our subjects were highly selected patients with emphysema at a single center, all with predominantly upper-lobe disease. Our results should not be applied to those patients who do not meet NETT criteria or to those with predominantly non–upper-lobe pulmonary emphysema. Finally, with no mortality and a short follow-up period, we are unable to determine whether changes in the BODE index after 1 year predict long-term prognosis. Longer follow-up of a larger cohort is needed.
In summary, we performed a prospective study of LVRS with no deaths with the inclusion criteria of NETT. LVRS significantly improved the BODE index and its FEV1 and dyspnea components after 1 year. Lower preoperative 6-minute walk distance and lower postwalk fatigue scores predicted greater improvements in the BODE index. We suggest future studies to confirm the BODE index as a useful surrogate end point.
We thank the physical therapists, respiratory therapists, and other staff members of the Jo-Ann F. LeBuhn Center for Chest Disease and Respiratory Failure at Columbia University Medical Center and New York Presbyterian Hospital.
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Supported by National Institutes of Health grant HL072739.
PII: S0022-5223(07)00292-9
doi:10.1016/j.jtcvs.2006.12.062
© 2007 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Refers to article:
- Lung-volume reduction surgery: A vanishing operation?
Volume 133, Issue 6 , Pages 1434-1438, June 2007
