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Division of Thoracic Surgery and Pulmonary Division, University Hospital, Zurich, Switzerland
Accepted for publication October 8, 2008.
* Address correspondence to Dr Weder, Division of Thoracic Surgery, Raemistr.100, University Hospital of Zurich, Zürich, CH- 8091, Switzerland (Email: walter.weder{at}usz.ch).
Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.
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Abstract |
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Methods: Two hundred fifty consecutive patients (105 women), mean (± standard deviation) age 64 ± 8.4 years, with advanced emphysema underwent bilateral thoracoscopic lung volume reduction surgery. Forced expiratory volume in 1 second was 28% ± 8% of predicted, 6-minute walking distance was 245 ± 118 m, and Medical Research Council dyspnea score was 3.5 ± 0.7. In 138 patients (55%) computed tomography revealed homogeneous emphysema (including 82 intermediate type) distribution and in 112 patients (45%) heterogeneous emphysema. Baseline characteristics were otherwise similar in the two groups that were prospectively observed for several years.
Results: Thirty-day mortality was 2.4%. Both groups revealed significant improvements 3 months after lung volume reduction surgery: in homogeneous emphysema, predicted forced expiratory volume in 1 second was 38% ± 14% (35% improvement), 6-minute walk distance was 324 ± 87 m, and dyspnea score was 1.8 ± 0.9 (p < 0.05 all outcomes). Corresponding results in heterogeneous emphysema were 44% ± 15% (61% improvement), 382 ± 95 m, and 1.3 ± 0.9 points (p < 0.05 versus baseline; not significant versus homogeneous). Median time until predicted forced expiratory volume in 1 second and 6-minute walk distance had returned to baseline was 36 months in both groups. One-year survival was similar in both groups. At 5 years, median survival without lung transplantation was 64% in the homogeneous and 73% in the heterogeneous group (Cox proportional hazard, 0.81; 95% confidence interval, 0.66 to 0.98; p = 0.03).
Conclusions: In selected patients with homogeneous pulmonary emphysema, lung volume reduction surgery can be successfully performed with low perioperative mortality. Significant improvements in dyspnea, lung function, and exercise capacity are maintained for several years.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Patients were selected for LVRS according to previously published criteria [15]. Briefly, severely symptomatic patients with advanced pulmonary emphysema (Modified Medical Research Council dyspnea score [16], [MRC] 
grade 2), severe airflow obstruction, and hyperinflation (forced expiratory volume in 1 second [FEV1] < 40% predicted, total lung capacity [TLC] > 120% predicted) were considered for LVRS if they have stopped smoking for at least 3 months. Emphysema distribution was assessed by computed tomography and lung perfusion scintigraphy, and classified into a markedly heterogeneous, a completely homogeneous, and an intermediate type as previously published [17]. For the purpose of the current analysis, the completely homogeneous and intermediate type emphysema showed a similar course of improvement by MRC dyspnea score, FEV1, residual volume [RV]/TLC, and walking distance (Fig 5) and were both termed "homogeneous," and the outcome of patients with homogeneous emphysema was compared with those with markedly heterogeneous emphysema. An extremely low functional reserve, ie, an FEV1 less than 20% predicted in combination with a diffusing capacity less than 20% predicted or advanced pulmonary parenchymal destruction (ie, "vanished lung") on computed tomography and comorbidities likely to entail a high perioperative mortality such as symptomatic cardiovascular disease or to affect survival such as malignant disorders were exclusion criteria for the operation from the beginning of the study.
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The lung was resected in areas that showed the most severe emphysematous destruction on imaging studies (computed tomographic scan and quantitative perfusion scan), typically either in the upper lobe or the basal segments of the lower lobe. In patients who had a combination of lower and upper lobe destruction, approximately 20% to 30% of the upper lobe was resected, in combination with the apical segment of the lower lobe. In homogeneously destroyed lungs, the site of resection was preferentially chosen in the upper lobes and the target amount of resection was the volume that was needed to restore the TLC as predicted, usually approximately 40% to 50% of both upper lobes.
Pulmonary function
Spirometry was performed and thoracic gas volumes were measured 10 minutes after inhalation of two puffs of salbutamol with a mass flowmeter and a body plethysmograph, respectively (6200 Autobox; Sensor Medics, Yorba Linda, CA). Diffusing capacity for carbon monoxide was measured with an infrared analyzer (Model 66200; Sensor Medics), which uses methane as an inert tracer gas. Criteria for acceptability and reproducibility and predicted normal values were according to the European Community of Coal and Steel [18].
Dyspnea was rated with the American Thoracic Society modified MRC dyspnea score [16].
Six-minute walking distance
The patients walked in the same hospital hallway without oxygen supplementation encouraged by a technician [19–21].
Arterial blood gases were sampled by puncturing the radial artery of the patient sitting at rest and breathing room air. Analysis was performed by an automated blood gas measurement system (AVL 995-S; AVL Medical Instruments, Schaffhausen, Switzerland).
Measurements were performed before LVRS, after 3 months, at 6 months, and then at semiannual intervals. Information on survival or death was obtained by contacting the physicians involved in the long-term care of the patients, and date of death was verified from their records.
Statistics
Data are expressed as mean (± standard deviation). Outcomes of patients with homogeneous versus heterogeneous emphysema were compared by Mann-Whitney U statistics and paired comparisons were performed by Mann-Whitney or Student's t tests. Frequency data were analyzed using 
2 statistics or Fisher's exact test where appropriate, and survival without lung transplantation was assessed by Kaplan–Meier and Cox proportional hazard analysis. A probability of less than 0.05 was considered significant.
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Results |
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Walking Distance
A significant improvement in walking distance was documented for up to 2 years after the intervention (Table 1). There was no statistical difference between the groups in the time until baseline values were reached again (hazard ratio, 0.96; 95% confidence interval, 0.8 to 1.1; log-rank test; p = 0.6; Fig 7).
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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We prospectively studied functional and symptomatic improvement and mortality in our single-center cohort of patients undergoing bilateral video-assisted LVRS since the start of our program 12 years ago. Shortness of breath, walking distance, and lung function improved to a degree comparable with the results of other large long-term series [3, 4, 10], with a low perioperative mortality of 2.4%. For example, the mean increase in FEV1 3 months after surgery in patients with homogeneous and heterogeneous emphysema of 0.24 L and 0.48 L, respectively, compares favorably with the corresponding improvement of 0.17 L reported by Geddes and associates [22] and the change in FEV1 at 6 months in the study by Ciccone and colleagies of 0.4 L [4]. Only three studies report detailed functional results beyond 2 years after bilateral LVRS in prospectively followed cohorts with more than 50 patients [4, 5, 23]. Results are comparable with our findings. Mean FEV1 was higher than preoperatively by 0.25 to 0.4 L at 6 months and between 0.08 and 0.2 L at 36 months. Ciccone and coworkers [4] found the mean FEV1 in the patients who could be followed at 5 years 0.1 L higher than before LVRS, which is similar to our results (Table 1). A principal aim of LVRS is the reduction in hyperinflation, which lasted up to 2 years in our patients with homogeneous emphysema. Only a few groups have studied the long-term effect of LVRS on hyperinflation. Fujimoto and colleagues [5] reported a reduction in hyperinflation for up to 3 years, and Ciccone and associates [4] found a reduction of RV/TLC lasting for up to 5 years. Changes in pulmonary function were associated with persistent improvements in exercise capacity. The mean increase in 6-minute walking distance 3 months after LVRS was 78 m in patients with homogeneous and 139 m in patients with heterogeneous emphysema, ie, almost twice as big as the minimally perceivable and clinically relevant change of approximately 50 m [24, 25] and greater than in several previously published series [4, 7, 26]. Furthermore, the course of the 6-minute walk distance after LVRS did not differ between the two groups (Fig 7).
When comparing functional results among various centers, emphysema morphology has to be strongly considered. The classification of emphysema morphology, which we have applied for the past 12 years, shares some similarities with the categories used in the NETT with respect to the distinction between heterogeneous and homogeneous emphysema. However, in the NETT, comparisons were performed between predominantly upper lobe and non–upper lobe subgroups whereas we categorized according to heterogeneity of disease independent of affected lobes. Therefore, a comparison between the NETT and our results is limited to some extent. Nonetheless, consistent with the NETT [10] and other trials [23, 27, 28], we found larger functional improvements in patients with heterogeneous as compared with homogeneous emphysema (Table 1). Patients with upper lobe predominance had better clinical and functional improvement than those with lower lobe predominance for reasons not completely understood. Most likely it is related more to the disease than a result of the surgical technique. This observation is consistent with other findings. Because the greater initial functional improvement in patients with heterogeneous emphysema also declined more rapidly in the first few months after LVRS, the intermediate to long-term results became similar between the two morphologic emphysema types as we had previously described [12]. Independent of the emphysema morphology, the values of FEV1 and the 6-minute walking distance had returned to values near baseline after a median period of 36 months (Fig 1), although patients perceived persistent improvements in dyspnea for a much longer time, ie, for 4 to 5 years (Table 1).
Our overall perioperative mortality was low with 2.4%. This is comparable to the perioperative mortality in other series of 2% to 4% [3, 4, 6, 10]. Even in patients with homogeneous emphysema, perioperative mortality was low (1%), and similar proportions of patients with homogeneous and heterogeneous emphysema survived for at least 1 year (93% and 94%, respectively). In a subgroup of NETT patients who had a very low FEV1 and diffusing capacity (<20% predicted) in combination with non–upper lobe emphysema, the 30-day mortality rate was excessively high (16%). We believe that excluding patients with homogeneous emphysema and extremely poor functional reserve has contributed to the relatively low perioperative and 1-year mortality in our series. During the subsequent years, heterogeneous disease was associated with superior survival even when corrected for potential confounders such as age, sex, body mass index, alpha1-antitrypsin deficiency, baseline pulmonary function, and exercise capacity in a Cox regression model (Fig 2). Although the 5-year survival without lung transplantation was lower in homogeneous compared with heterogeneous emphysema (64% versus 73%), it still compares favorably with that of patients in the medical arm of the NETT trial (42% 5-year survival). It is not clear whether the differences in intermediate and long-term survival associated with emphysema morphology in our cohort relate to differences in the disease process (ie, the amount of inflammation, for example) or to differences in mechanical properties of the lung. Furthermore, we cannot exclude that tissue was inadvertently removed less radically in homogeneous than in heterogeneous emphysema during LVRS.
The target location and the extent of resection may be relatively well defined in patients with a heterogeneous type of emphysema because the nonperfused area is functionless. In the homogeneous type, lung parenchyma with some function has to be resected by definition. We were very careful in selecting the ideal amount of resection and intended to achieve a lung size after surgery with a volume according to the predicted TLC. This was most easily achieved by resecting in both upper lobes. Furthermore, selection of patients with homogeneous emphysema has to be done even more carefully than that of patients with heterogeneous disease as tissue with some remaining function will be resected. Especially a very low diffusing capacity below 20% predicted and scarring of the lungs, which indicates a possibly difficult postoperative course, should be strictly respected.
In conclusion, we show that patients with severe emphysema associated with massive hyperinflation may benefit from LVRS independent of heterogeneity of emphysema in terms of symptoms, exercise capacity, and pulmonary function at a relatively low perioperative risk. Although long-term survival without lung transplantation is superior in patients with heterogeneous disease, LVRS may provide substantial symptomatic and functional improvements in selected patients with homogeneous emphysema.
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Discussion |
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Can you also briefly mention, for the intermediate and the homogeneous group of patients, what surgical techniques were utilized for these patients?
In the UK, David Waller and William Walker have advocated unilateral LVRS (lung volume reduction surgery) and have published good results on that. Does your group have any experience with unilateral LVRS for either the heterogeneous or nonheterogeneous group of patients?
Can you let us know your personal thoughts on why there's a faster decline in the pulmonary function measurements of the heterogeneous group of patients?
Lastly, I was hoping Walter would be here as he has been involved with airway bypass work as we have. Do you see the role of airway bypass in the treatment of the nonheterogeneous group of patients, and how would that compete with or complement the surgical options? Thank you.
DR TUTIC: Thank you very much for the questions.
In a previously published study we evaluated various physiologic parameters as well as clinical judgement as predictors of response to LVRS. Hyperinflation assessed by RV/TLC ratio among other factors correlated positively with outcome.
In patients with homogeneous emphysema we resect as much lung volume on each side that we restore the normal predicted TLC. Since there is no distinct target area defined like in a heterogeneous type of emphysema, we usually resect a hockey-stick shaped piece of lung in both upper lobes. In the intermediate heterogeneous type we select whenever possible an area for resection which has at least some destruction on CT.
We did not study the role of sequential unilateral LVRS and apply an unilateral approach for patients with a predominant unilateral emphysema or for redo-LVRS.
We assume that the faster decline of the improvement in FEV1 after LVRS in the heterogeneous type has to do with higher tension forces in the lung parenchyma after resection since we postulate that more volume is resected in the heterogeneous type.
DR DAVID A. WALLER (Leicester, UK): Could I just make a plea? I don't agree with the arbitrary division of emphysema into these groups because it's a spectrum.
DR TUTIC: We agree that emphysema morphology covers a large spectrum and our classification is a simplification but very helpful for patient selection for LVRS. However, it is not difficult to recognize the homogeneous type in the CT where no difference in destructions is seen throughout the whole lung. Additionally, it is straightforward to identify patients with a clear heterogeneity in emphysema destruction. Then we have the cases which are in between. This is indeed a melting pot of different subtypes of emphysema morphology.
DR WALLER: And all we really try to do is to remove as little functioning gas-exchanging tissue in this operation while reducing hyperinflation. And, therefore, I don't agree that it's related to morphology. It's related to physiology. And we hardly look at CT (computed tomographic) scans now. We look at ventilation–perfusion scans to select these cases.
So I agree with your conclusions, but I don't agree with your arbitrary division. Do you have any comment on that?
DR TUTIC: Perfusions scintigraphy is used additionally in all cases to confirm our assessment of the CT scans and to identify target areas for resection.
DR DANIEL L. MILLER (Atlanta, GA): See, in the U.S. our hands are tied because of being reimbursed by CMS (Centers for Medicare and Medicaid Services) at the 44 centers, it has to have heterogenic disease, which was found from the NET (National Emphysema Treatment) trial.
DR MILTON SAUTE (Petah-Tikva, Israel): Congratulations on your work. You didn't answer the first question of our colleague. How do you plan the operation in these homogeneous cases? First of all, what is the ideal case for a homogeneous resection? How do you perform the operation? Is it the same way as in a heterogeneous case?
DR TUTIC: It is a bilateral thoracoscopic stapler resection in all cases. In patients with homogeneous emphysema, we resect tissue which contributes to gas exchange. This means that we have to be cautious not to resect too much tissue. We resect approximately the volume to restore normal TLC, certainly not more. Usually the resection is performed in both upper lobes.
DR DIRK E. M. VAN RAEMDONCK (Leuven, Belgium): You've shown us a curve with freedom from transplantation.
DR TUTIC: Yes.
DR VAN RAEMDONCK: And I noticed that about 80% of the patients after 5 years were transplanted.
DR TUTIC: This is not the case.
DR VAN RAEMDONCK: Are these really transplanted patients or patients on the waiting list for transplantation?
DR TUTIC: These are patients without transplantation.
DR VAN RAEMDONCK: Without transplant?
DR TUTIC: Overall we have transplanted 9 patients after LVRS.
DR VAN RAEMDONCK: But your curve is going down to 20%—
DR TUTIC: The long-term survival for the homogeneous type is around 20% after 10 years.
DR VAN RAEMDONCK: —so it means that 80% were transplanted.
DR TUTIC: No, it includes the transplant free survival.
DR VAN RAEMDONCK: And if I remember well from the talks with Walter Weder, he's not transplanting many patients for emphysema but rather for cystic fibrosis.
DR TUTIC: Yes. In our transplant cohort only 28% are transplanted for emphysema which allows us to allocate lungs to patients with cystic fibrosis in 38%.
DR VAN RAEMDONCK: Okay.
DR TUTIC: The patients who were transplanted were excluded from the survival curve.
DR VAN RAEMDONCK: Okay. I see.
DR JESSICA S. DONINGTON (New York, NY): You showed us Kaplan–Meier curves demonstrating survival without transplantation for the heterogeneous and nonheterogeneous patient populations; is the difference between those curves mostly a result of respiratory failure causing death or an increased rate of patients who went on to transplantation?
DR TUTIC: Most patients died on the long term due to respiratory failure.
DR SEBASTIEN GILBERT (Pittsburgh, PA): I hope I didn't miss it in the presentation, but did you look at exercise capacity in your patients and stratify it according to what has been previously described in NETT as low- and high-exercise capacity. Also, in your heterogeneous distribution group, would patients with lower lobe predominant emphysema undergo LVRS or were they considered nonsurgical candidates?
DR TUTIC: Patients with lower lobe emphysema were not excluded from surgery. The improvement in FEV1 was less than in upper lobe emphysema but the difference did not reach statistical significance. We did not use exercise capacity for an outcome analysis. Patients who were not limited in their daily activity were not treated. Furthermore, the principal goal for most of the patients is not to prolong their survival which was the main parameter in the NETT rather than to improve quality of life.
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Acknowledgments |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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References |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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This article has been cited by other articles:
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  D. Van Raemdonck and V. Ninane Lung volume reduction for severe emphysema: do we need a scalpel or a scope? Eur. Respir. Rev., September 1, 2010; 19(117): 242 - 247. [Abstract] [Full Text] [PDF]
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 H. E. Fessler and D. Feller-Kopman Helping the homogeneous Eur. Respir. J., July 1, 2010; 36(1): 8 - 9. [Full Text] [PDF]
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), intermediate (gray-filled circles), homogeneous (
). (LVRS = lung volume reduction surgery.)
