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J Thorac Cardiovasc Surg 2007;133:1434-1438
© 2007 The American Association for Thoracic Surgery


General Thoracic Surgery

Lung-volume reduction surgery for pulmonary emphysema: Improvement in body mass index, airflow obstruction, dyspnea, and exercise capacity index after 1 year

David J. Lederer, MDa,b, Byron M. Thomashow, MDa,b, Mark E. Ginsburg, MDa,c, John H.M. Austin, MDa,d, Matthew N. Bartels, MD, MPHa,e, Chun K. Yip, MDa,b, Patricia A. Jellen, MSNa, Frances L. Brogan, MSNa, Steven M. Kawut, MD, MSb, Roger A. Maxfield, MDa,b, Angela M. DiMango, MDa,b, Paul F. Simonelli, MD, PhDa,b, Lyall A. Gorenstein, MDa,c, Gregory D.N. Pearson, MD, PhDa,d, Joshua R. Sonett, MDa,c,*

a New York Presbyterian Lung Volume Reduction Surgery Program, Columbia University College of Physicians and Surgeons, New York, NY
b Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY
c Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY
d Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY
e Department of Rehabilitation Medicine, Columbia University College of Physicians and Surgeons, New York, NY.

Received for publication June 12, 2006; revisions received November 15, 2006; accepted for publication December 12, 2006.

* Address for reprints: Joshua R. Sonett, MD, Columbia University College of Physicians and Surgeons, Division of Cardiothoracic Surgery, 622 W 168th St, PH 14, Room 104, New York, NY 10032. (Email: js2106{at}columbia.edu).


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 
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.



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



    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 
GoChronic 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 2000.1Go 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.2-4Go

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.4Go 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.5Go 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.5Go The BODE index was a better predictor of mortality than was FEV1 alone.


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TABLE 1 Components of body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index
 
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.6,7Go


    Materials and Methods
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 
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). 8Go 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.4Go All exercise testing was performed after pulmonary rehabilitation. The BODE index was calculated as described by Celli and colleauges5Go (Table 1).


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TABLE 2 Inclusion and exclusion criteria
 
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.9Go We therefore imputed missing 1-year data with the worst 1-year values in the entire cohort (worst rank score imputation).10Go 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
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 
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
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 
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 ß2-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.


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TABLE 3 Baseline characteristics
 
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.


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TABLE 4 Surgical outcomes
 
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 PaO 2 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.


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TABLE 5 One year outcomes after lung-volume reduction surgery
 
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
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 
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.11,12Go Imfeld and coworkers11Go 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.4Go 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.


See related editorial on page 1412.

 


    Acknowledgments
 
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.


    Footnotes
 
Supported by National Institutes of Health grant HL072739.


    References
 Top
 Abstract
 Introduction
 Materials and Methods
 Statistical Analysis
 Results
 Discussion
 References
 

  1. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance—United States, 1971-2000. MMWR Surveill Summ 2002;51:1-16.[Medline]
  2. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet 1981;1:681-686.[Medline]
  3. Celli BR, MacNee W, ATS/ERS Task Force Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. [published erratum appears in Eur Respir J. 2006;27:242] Eur Respir J 2004;23:932-946.[Free Full Text]
  4. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059-2073.[Medline]
  5. 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;350:1005-1012.[Medline]
  6. Lederer DJ, Jellen PA, Sonett JR, Austin JH, Brogan FL, Ginsburg ME, et al. Lung volume reduction surgery improves the BODE index. [abstract] Chest 2005;128:179S.[Abstract]
  7. Lederer DJ, Sonett JR, Jellen PA, Bartels MN, Yip CK, DiMango AM, et al. Pre-operative exercise capacity predicts BODE index improvement one year after lung volume reduction surgery [abstract]. Proc Am Thorac Soc 2006;3:A851.
  8. Rationale and design of the National Emphysema Treatment Trial (NETT): a prospective randomized trial of lung volume reduction surgery. J Thorac Cardiovasc Surg 1999;118:518-528.[Free Full Text]
  9. Butler CW, Snyder M, Wood DE, Curtis JR, Albert RK, Benditt JO. Underestimation of mortality following lung volume reduction surgery resulting from incomplete follow-up. Chest 2001;119:1056-1060.[Medline]
  10. Lachin JM. Worst-rank score analysis with informatively missing observations in clinical trials. Control Clin Trials 1999;20:408-422.[Medline]
  11. Imfeld S, Bloch KE, Weder W, Russi EW. The BODE index after lung volume reduction surgery correlates with survival. Chest 2006;129:873-878.[Medline]
  12. Cote CG, Celli BR. Pulmonary rehabilitation and the BODE index in COPD. Eur Respir J 2005;26:630-636.[Abstract/Free Full Text]

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