J Thorac Cardiovasc Surg 2008;135:931-937
© 2008 The American Association for Thoracic Surgery
Cardiothoracic Transplantation |
Native lung volume reduction surgery relieves functional graft compression after single-lung transplantation for chronic obstructive pulmonary disease
T. Brett Reece, MDa,
John D. Mitchell, MDa,
Martin R. Zamora, MDb,
David A. Fullerton, MDa,
Joseph C. Cleveland, MDa,
Marvin Pomerantz, MDa,
Dennis M. Lyu, MDb,
Frederick L. Grover, MDa,
Michael J. Weyant, MDa,*
a Division of Cardiothoracic Surgery, University of Colorado Health Sciences Center, Denver, Colo
b Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colo
Received for publication June 23, 2007; revisions received September 20, 2007; accepted for publication October 22, 2007.
* Address for reprints: Michael J. Weyant, MD, 4200 E 9th Ave, Suite C310, Denver, CO 80262. (Email: michael.weyant{at}uchsc.edu).
 |
Abstract
|
|---|
Objective: Single-lung transplantation is an accepted treatment for end-stage lung disease caused by chronic obstructive pulmonary disease. A complication unique to single-lung transplantation for chronic obstructive pulmonary disease is graft dysfunction due to compression caused by native lung hyperinflation. We hypothesized that patients with functional compromise from native lung hyperinflation would benefit from native lung volume reduction surgery.
Methods: The charts of all patients undergoing single-lung transplantation for chronic obstructive pulmonary disease were reviewed for lung volume reduction surgery of their native lung. Data regarding length of stay, surgical morbidity and mortality, overall survival, type of lung volume reduction surgery, and pulmonary function were recorded to evaluate the effect of lung volume reduction surgery.
Results: Between February 1992 and May 2007, 206 single-lung transplantations were performed for chronic obstructive pulmonary disease. Ten (5%) patients had clinically significant graft compression from native lung hyperinflation. After excluding other causes for functional decline, these patients underwent a modified lung volume reduction surgery between 12 and 142 months after single-lung transplantation (mean, 50 months). Lung volume reduction surgery consisted of anatomic resection. Two (20%) of 10 patients died during their hospitalization. Of the remaining 8 patients, 7 (87.5%) have demonstrated functional improvement on the basis of forced expiratory volume in 1 second improving from 12% to 200% (mean improvement, 57%). Within 6 months of lung volume reduction surgery, mean 6-minute walk values improved significantly (866 to 1055 feet), whereas desaturation with exertion decreased significantly.
Conclusions: Lung volume reduction surgery by means of formal lobectomy in patients with native lung hyperinflation undergoing single-lung transplantation and significant graft compression appears feasible. Additionally, improvements in forced expiratory volume in 1 second can be accomplished in nearly all properly selected patients. Lung volume reduction surgery should be considered in patients with decreasing graft function caused by graft compression from native lung hyperinflation.
Abbreviations and Acronyms BOS = bronchiolitis obliterans syndrome; COPD = chronic obstructive pulmonary disease; CT = computed tomography; FEV1
= forced expiratory volume in 1 second; LVRS = lung volume reduction surgery; NLH = native lung hyperinflation; SLT = single-lung transplantation
|
Introduction
|
|---|
Single-lung transplantation (SLT) is an accepted treatment for end-stage lung disease caused by chronic obstructive pulmonary disease (COPD). SLT for COPD has accounted for almost 40% of lung transplantations according to the most recent report from the International Society for Heart and Lung Transplantation Registry.1
Moreover, from 1995 through 2005, more than 67% of lung transplantations for COPD were single-lung rather than double-lung transplantations.
A complication unique to SLT for COPD is graft dysfunction due to compression caused by native lung hyperinflation (NLH).2 Clinically relevant graft compression is characterized by a decrease in clinical function as measured by a decrease in forced expiratory volume in 1 second (FEV1), exercise tolerance, and increased oxygen requirements in the setting of radiographic evidence of graft compression. Lung volume reduction surgery (LVRS) has been proposed as a method of treatment for this phenomenon.3-7
Table 1 summarizes the most comprehensive reports in the literature on lung volume reduction surgery after single lung transplants for COPD.
The purpose of this study was to determine whether native lung resection improves overall lung function in the setting of transplant graft compression caused by NLH. We hypothesized that patients with graft compromise caused by NLH would benefit from LVRS of the native lung. This study reports our experience in 10 patients undergoing LVRS for NLH and graft compression after SLT for COPD.
|
Materials and Methods
|
|---|
Approval of this study was obtained from the Colorado Multiple Institutional Review Board. The charts of all patients undergoing SLT for COPD at our institution between February 1992 and May 2007 were reviewed to capture those patients undergoing LVRS for SLT graft compression. Functional decline was defined primarily as a decrease in FEV1, but a decrease in 6-minute walk values and an increase in the need for supplemental oxygen also contributed to this determination. Graft compression was suspected with chest radiographic findings of progressive mediastinal shift (
Figure 1). Chest computed tomography (CT) was used to confirm mediastinal shift in the setting of an incremental decrease in transplanted lung volume. Other CT findings included evidence of compression of the intragraft vasculature or a large bronchus. Patients underwent bronchoscopy with transbronchial biopsy to rule out airway stenoses or bronchomalacia or acute or chronic rejection. A careful evaluation was performed to rule out other causes of decreased allograft function, as shown in
Figure 2. The modified LVRS consisted of anatomic resections, both lobectomy and segmentectomy, rather than the more traditional extensive buttressed wedge resections.
View larger version (76K):
[in this window]
[in a new window]
|
Figure 1. Evolution of graft compression on chest radiographic analysis. These plain films show the progression of graft compression with increased right lung volume and mediastinal shift from after transplantation to before lung volume reduction surgery (LVRS). The last film demonstrates resolution of the compression after LVRS.
|
|
View larger version (17K):
[in this window]
[in a new window]
|
Figure 2. Algorithm for lung volume reduction surgery (LVRS) after single-lung transplantation for chronic obstructive pulmonary disease. The steps for working up a decrease in pulmonary function in single-lung transplantation for chronic obstructive pulmonary disease are shown. native lung hyperinflation (NLH) is a diagnosis of exclusion, and therefore every attempt is made to exclude infection, acute rejection, and bronchiolitis obliterans syndrome (BOS). The workup, in bold, includes findings and reasons for the test. FEV1, Forced expiratory volume in 1 second; CXR, chest radiography; VQ, ventilation/perfusion.
|
|
Data were recorded regarding outcomes of LVRS, including length of hospital stay, perioperative morbidity, and mortality. Date and timing of both the original transplantation and the LVRS were noted. Furthermore, the patient's overall survival and specific LVRS procedure were reviewed. Most importantly, pulmonary function test results were recorded from evaluation for transplantation to the present. The patients' FEV1, 6-minute walk values, and oxygen requirements were used as objective markers to determine the overall effect of LVRS procedure by comparing them at their peak after transplantation, before LVRS, and postoperatively after LVRS.
Statistical comparisons were performed by an independent statistician using repeated-measures analysis of variance, and differences were confirmed with Tukey HSD multiple-comparison analysis.
|
Results
|
|---|
From 404 lung transplantations, 206 SLTs were performed for COPD. Ten (5%) patients experienced significant functional graft compression and underwent LVRS. All patients underwent a modified LVRS consisting primarily of anatomic resections, as follows: 3 lower lobectomies, 5 upper lobectomies, a bilobectomy, and a lower lobe segmentectomy with upper lobe wedge resection. Three of the 10 patients also underwent intercostal muscle flap reinforcement of the bronchus. All LVRSs were performed by one of 3 surgical staff whose practice consists solely of thoracic surgery.
The mean time between transplantation and LVRS was 50 months (range, 12–142 months). The decrease in FEV1 between SLT and LVRS was 40% (range, 11%–70%) from transplantation to consideration for LVRS. Two patients died in the perioperative period at 17 and 34 days, respectively, after the operation. One death stemmed from bronchial stump complications, whereas the other patient was ultimately found to have bronchiolitis obliterans syndrome (BOS) on autopsy. Two other patients required reintubation during their hospital course. Three patients had postoperative pneumonia, 2 cases of which resulted in hospital deaths. Five had prolonged air leak of greater than 7 days. One patient had acute renal failure requiring hemodialysis. The intensive care unit stay averaged 13 days (range, 4–34 days). Hospital stay averaged 18 days (range, 8–34 days) after LVRS.
Follow-up of the survivors from LVRS averaged 21 months (range, 9–71 months). After discharge, all patients except 1 were still alive, with the 1 late death being a result of complications from posttransplantation lymphoproliferative disease. Of the 8 patients who left the hospital, 7 (87.5%) demonstrated significant functional recovery, as shown by improvement of FEV1 to the previous baseline value (
Figure 3). FEV1 improvement averaged 57% (range, 12%–200%). Improvement in FEV1 surpassed the previous posttransplantation peak in 1 patient. Among hospital survivors, 7 of 8 patients desaturated with exertion (decrease of 4% or to <90%) before LVRS, but none of the 8 decreased their oxygen saturation with exercise at their peak after transplantation. After LVRS, only 2 of 8 patients desaturated with exertion. Additionally, the impaired 6-minute walk values of these patients demonstrated s significant reduction from their peak after transplantation to the time of LVRS, with a return to baseline around 6 months after LVRS. Finally, mean oxygen saturation was 94.5% at rest after transplantation. This decreased significantly to 90% before LVRS, with significant recovery to 93.4% after LVRS. The results of the 6-minute walk and resting peripheral oxygen saturation measurements are depicted in
Figure 4. The specific procedures and outcomes of each patient are summarized in
Table 2.
View larger version (17K):
[in this window]
[in a new window]
|
Figure 3. Changes in forced expiratory volume in 1 second (FEV1). The graft depicts individual changes in FEV1 from after transplantation to after LVRS by each patient. On average, there was significant improvement, and all but 1 of the hospital survivors demonstrated benefit on the basis of FEV1 from the procedure. The mean FEV1 at each point is depicted by the thick gray line with the diamond markers. *Significant change from after transplantation and after lung volume reduction surgery (LVRS; P < .01).
|
|
View larger version (13K):
[in this window]
[in a new window]
|
Figure 4. Changes in pulmonary function: A, changes in 6-minute walk values; B, changes in room air oxygen saturation. These 2 graphs show the respective changes in mean distance during 6-minute walks and room air oxygen from after transplantation through the clinical native lung hyperinflation to after lung volume reduction surgery (LVRS). Both markers of clinical pulmonary function showed a decrease from peak after transplantation, which was recovered to baseline in the majority of patients within 6 months of LVRS. *Significant change from after transplantation and after LVRS, P < .01).
|
|
|
Discussion
|
|---|
Although the optimal approach to end-stage COPD is argued, the International Society for Heart and Lung Transplantation Registry demonstrates that SLT for COPD has been the most common lung transplantation procedure performed.1 The native lung in these patients can continue to overinflate, which does not usually affect overall pulmonary function. However, a small subset of these patients has compromised function of the transplanted lung as a result of compression by the native lung. This transplant lung compression can manifest with increased oxygen requirements, deterioration in pulmonary function tests, and significant reduction in exercise capacity. The algorithm used for evaluating these patients for LVRS is depicted in Figure 2. Although all patients are followed with serial chest radiography, chest CT scans can facilitate diagnosis in these patients, with demonstration of increasing native lung expansion at the cost of allograft volume. Other CT findings included evidence of compression of the intragraft vasculature or a large bronchus. Patients underwent bronchoscopy to rule out airway stenoses or bronchomalacia and transbronchial biopsies to evaluate for acute or chronic rejection. It is critical that chronic rejection or BOS is ruled out before LVRS because patients with BOS do very poorly with lung surgery. This might not always be possible, but the lack of a mosaic pattern or air trapping on CT scanning or patchy perfusion defects on perfusion scintigraphic analysis suggest the absence of BOS.8,9
The National Emphysema Treatment Trial showed that resection of focal areas of emphysematous lung can benefit select patients with COPD.10 LVRS is intended to relieve compression of more normal areas of lung through resection of the most diseased, least functional areas of the lung. This was shown to be most effective in patients with relatively focal disease (upper lobe predominant). In regard to the current study, all the patients have focal COPD limited to their native lung but were not believed to be LVRS candidates before transplantation. Similar to traditional LVRS, the most hyperinflated lobe or lobes of the native lung were targeted for resection in the present study.
Lung resections in patients undergoing lung transplantation are considered high risk for almost all patients. Pulmonary resection for these patients might be at even higher risk given the combination of immunosuppression and an extremely abnormal native lung. However, there is a growing body of literature documenting the feasibility of operating on these patients. Fitton and colleagues11 published a series of 12 lung resections performed on lung transplant recipients for various indications, including graft compression, infection, and neoplasm. Overall, their high-risk cohort did relatively well, with 85% surviving a month. Of note, the subgroup undergoing wedge resection did notably worse. A proposed mechanism is that these patients would have difficulty healing the long suture line of a wedge resection. They conclude that with medical optimization, lung resections in lung transplant recipients is high risk but can be undertaken with acceptable morbidity and chance for success. Other reports in the literature substantiate the feasibility of lung resections after lung transplantation.3,4
Several smaller series of LVRS in patients undergoing lung transplantation have been published, but they include limited data regarding outcome beyond a year of follow-up.3-7 Case reports of lung resections for NLH can be found back to 1996. These reports include both lobectomies and wedge resections. Schulman and associates12 reported using LVRS with disabling BOS. They performed a more traditional LVRS with native lung wedge resection. In their study the majority of patients showed some improvement in pulmonary function with relief of allograft compression. Although they found native lung LVRS for BOS salvaged some respiratory function, the benefits were concluded to be limited in magnitude and duration by the severity of the chronic rejection. They reported that 3 of 7 reported patients died within a year of their procedure after LVRS, despite documented early improvements in pulmonary function. Fitton and colleagues11 reported 4 native lung reductions for NLH in their report on lung resections in patients undergoing lung transplantation. Of the remaining 2 patients, one lived for more than 3 years after LVRS, and the other was still alive more than a year out at the time of their publication. These studies demonstrate that LVRS is feasible in patients undergoing lung transplantation but that patient selection, in particular avoiding operations in patients with BOS, and timing of surgical intervention are probably the most important determinants of longer-term postoperative outcomes for these patients.
The present series represents the largest series of native lung LVRS in SLT for COPD found in the literature. The development of NLH leading to clinically significant allograft compression has been uncommon, with 10 patients undergoing native lung LVRS among 206 SLTs for COPD. Overall, patients undergoing LVRS for NLH faired well in our study. Two patients died during their hospital course, which is consistent with the National Emphysema Treatment Trial mortality rate for LVRS in nonimmunosuppressed patients.2 The development of pneumonia was a difficult problem for these patients to overcome because the 2 deaths both included pneumonia. One of these 2 patients with pneumonia was found later to have BOS, which complicated the pulmonary course. One patient who had pneumonia during the hospital course left the hospital. Seventy percent of the patients enjoyed functional improvement on the basis of FEV1 or 6-minute walk values after LVRS. By using the algorithm depicted in Figure 2, patients can be well selected for LVRS to possibly reset the baseline of their pulmonary function to their peak after transplantation. This reestablishment of baseline lung function has been demonstrated by improved 6-minute walk values, oxygen requirements, room air saturations at rest, and FEV1.
Given the less-than-optimal reports of both wedge resections and traditional LVRS in the SLT literature, anatomic resections were chosen in an effort to facilitate pulmonary healing. This strategy appears to have been successful, but prolonged air leak still occurred in half of the patients and significantly extended hospital stays. The extended hospital stays and incidence of complications demonstrate the level of care needed for these patients. Although intense pulmonary rehabilitation was required for recovery from their lung resections, 7 of 8 patients discharged from the hospital saw improved pulmonary function, as demonstrated by their improved FEV1. In terms of late follow-up, 7 of 8 hospital survivors are alive at a mean of 20 months after LVRS.
These data demonstrate that LVRS by means of formal anatomic resection in patients undergoing SLT with significant graft compression from NLH is feasible. Although hospital stay and pulmonary rehabilitation can be intensive, improvements in lung function can be accomplished in nearly all properly selected patients, with excellent long-term survival. In conclusion, LVRS should be considered in patients with decreasing graft function caused by graft compression from NLH.
|
Footnotes
|
|---|
Read at the Thirty-third Annual Meeting of the Western Thoracic Surgical Association, Santa Ana Pueblo, NM, June 27–30, 2007.
|
References
|
|---|
- Trulock EP, Edwards LB, Taylor DO, Boucek MM, Keck BM, Hertz MI, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult lung and heart-lung transplantation report—2006. J Heart Lung Transplant 2006;25:880-892.[Medline]
- Weill D, Torres F, Hodges TN, Olmos JJ, Zamora MR. Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema. J Heart Lung Transplant 1999;18:1080-1087.[Medline]
- Anderson MB, Kriett JM, Kapelanski DP, Perricone A, Smith CM, Jamieson SW. Volume reduction surgery in the native lung after single lung transplantation for emphysema. J Heart Lung Transplant 1997;16:752-757.[Medline]
- Kuno R, Kanter KR, Torres WE, Lawrence EC. Single lung transplantation followed by contralateral bullectomy for bullous emphysema. J Heart Lung Transplant 1996;15:389-394.[Medline]
- Le Pimpec-Barthes F, Debrosse D, Cuenod CA, Gandjbakhch I, Riquet M. Late contralateral lobectomy after single-lung transplantation for emphysema. Ann Thorac Surg 1996;61:231-234.[Abstract/Free Full Text]
- Kroshus TJ, Bolman 3rd RM, Kshettry VR. Unilateral volume reduction after single-lung transplantation for emphysema. Ann Thorac Surg 1996;62:363-368.[Abstract/Free Full Text]
- Venuta F, De Giacomo T, Rendina EA, Della Rocca G, Flaishman I, Guarino E, et al. Thoracoscopic volume reduction of the native lung after single lung transplantation for emphysema. Am J Respir Crit Care Med 1998;157:292-293.[Medline]
- Konen E, Gutierrez C, Chaparro C, Murray CP, Chung T, Crossin J, et al. Bronchiolitis obliterans syndrome in lung transplant recipients: can thin-section CT findings predict disease before its clinical appearance?. Radiology 2004;231:467-473.[Abstract/Free Full Text]
- Hardoff R, Steinmetz AP, Krausz Y, Bar-Sever Z, Liani M, Kramer MR. The prognostic value of perfusion lung scintigraphy in patients who underwent single-lung transplantation for emphysema and pulmonary fibrosis. J Nucl Med 2000;41:1771-1776.[Abstract/Free Full Text]
- 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]
- Fitton TP, Bethea BT, Borja MC, Yuh DD, Yang SC, Orens JB, et al. Pulmonary resection following lung transplantation. Ann Thorac Surg 2003;76:1680-1685.[Abstract/Free Full Text]
- Schulman LL, O'Hair DP, Cantu E, McGregor C, Ginsberg ME. Salvage by volume reduction of chronic allograft rejection in emphysema. J Heart Lung Transplant 1999;18:107-112.[Medline]
This article has been cited by other articles:
|
|
|
|
 
G. Massard, N. Santelmo, P.-E. Falcoz, and R. Kessler
Noninfectious complications
Lung Transplantation,
June 7, 2010;
177 - 193.
[Abstract]
[Fulltext]
[PDF]
|
|
|
|
|
|
|
W. van der Bij and M. Reynaud-Gaubert
Outcome and functional results
Lung Transplantation,
June 7, 2010;
238 - 250.
[Abstract]
[Fulltext]
[PDF]
|
|
|
|
|
|
|
J. G. Augoustides, S. M. Watcha, A. Pochettino, and D. R. Jobes
Early tracheal extubation in adults undergoing single-lung transplantation for chronic obstructive pulmonary disease: pilot evaluation of perioperative outcome
Interact CardioVasc Thorac Surg,
October 1, 2008;
7(5):
755 - 758.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
