Effect of Lung-Volume–Reduction Surgery in Patients with Severe Emphysema
Duncan Geddes, F.R.C.P., Michael Davies, M.R.C.P., Hiroshi Koyama, Ph.D., David Hansell, F.R.C.R., Ugo Pastorino, M.D., John Pepper, F.R.C.S., Penny Agent, M.C.S.P., Paul Cullinan, M.R.C.P., Stephanie J. MacNeill, M.Sc., and Peter Goldstraw, F.R.C.S.
Background Although many patients with severe emphysema haveundergone lung-volume–reduction surgery, the benefitsare uncertain. We conducted a randomized, controlled trial ofthe surgery in patients with emphysema. Patients with isolatedbullae were excluded because such patients are known to improveafter bullectomy.
Methods Potentially eligible patients were given intensive medicaltreatment and completed a smoking-cessation program and a six-weekoutpatient rehabilitation program before random assignment tosurgery or continued medical treatment. After 15 patients hadbeen randomized, the entry criteria were modified to excludepatients with a carbon monoxide gas-transfer value less than30 percent of the predicted value or a shuttle-walking distanceof less than 150 m, because of the deaths of 5 such patients(3 treated surgically and 2 treated medically).
Results Of the 174 subjects who were initially assessed, 24were randomly assigned to continued medical treatment and 24to surgery. At base line in both groups, the median forced expiratoryvolume in one second (FEV1) was 0.75 liter, and the median shuttle-walkingdistance was 215 m. Five patients in the surgical group (21percent) and three patients in the medical group (12 percent)died (P=0.43). After six months, the median FEV1 had increasedby 70 ml in the surgical group and decreased by 80 ml in themedical group (P=0.02). The median shuttle-walking distanceincreased by 50 m in the surgical group and decreased by 20m in the medical group (P=0.02). There were similar changeson a quality-of-life scale and similar changes at 12 monthsof follow-up. Five of the 19 surviving patients in the surgicalgroup had no benefit from the treatment.
Conclusions In selected patients with severe emphysema, lung-volume–reductionsurgery can improve FEV1, walking distance, and quality of life.Whether it reduces mortality is uncertain.
Lung-volume–reduction surgery has been performed in thousandsof people with emphysema in recent years.1 More than 30 separatereports of over 2000 operations have found substantial and clinicallyrelevant improvements in lung function, walking distance, andquality of life.2,3,4,5,6,7,8 Nevertheless, the clinical benefitsof the procedure have been questioned; private insurers andgovernmental organizations have refused to pay for the operation.The American Thoracic Society, together with others, has emphasizedthe need for randomized, controlled trials.9,10,11,12 Such trialsare needed for several reasons. First, patient selection andmethods of rehabilitation may affect the apparent improvementsassociated with surgery. Second, surgery may produce an initialimprovement at the cost of a subsequent accelerated decline.Third, some series have included patients with bullae, whosecondition is known to improve after bullectomy. Fourth, thereis substantial operative morbidity, and reported operative mortalityvaries from 0 to 19 percent.1,2,3,4,5,6,7 Finally, lung-volume–reductionsurgery is expensive, and there are many millions of potentialcandidates. A true comparative analysis is therefore needed,with a control group randomly assigned to receive the same intensiverehabilitation and medical management as that given to the patientswho undergo surgery.
From April 1996 through February 1999, we enrolled patientswith emphysema but without isolated bullae in a randomized,controlled trial of lung-volume–reduction surgery. Wereport the results for 48 patients who were followed for periodsranging from 6 to 12 months.
Methods
Trial Design
Patients were enrolled between April 1996 and February 1999.They were referred by specialist pulmonary physicians to beconsidered for lung-volume–reduction surgery in the contextof a randomized, controlled trial. Patients were informed aboutthe trial and the risks and benefits of surgery. The entry criteriawere severe emphysema, as shown on computed tomography (CT),with no restriction on the pattern or distribution of the emphysema;an age of less than 75 years; a forced expiratory volume inone second (FEV1) greater than 500 ml; use of oxygen for lessthan 18 hours per day; a corticosteroid dose of less than 10mg per day; and a partial pressure of arterial carbon dioxideof less than 45 mm Hg. Patients with asthma, previous thoracicsurgery, or other serious medical conditions were excluded.
The patients were given medical treatment consisting of a smoking-cessationprogram; trial therapy with prednisolone (30 mg per day fortwo weeks); inhaled beta-adrenergic agonists and anticholinergicdrugs at optimal doses; oral theophylline, with the responsejudged on the basis of symptoms and spirometric measures; oralantibiotics to be kept at home for use when needed for chestinfections; and vaccination against influenza and pneumococcus.Patients without any clear contraindications on initial assessmentwere entered into a six-week program of outpatient rehabilitation,consisting of physiotherapy and occupational therapy, with nursing,dietetic, and social services. Physiotherapy included gradedwalking, arm and leg exercises, and thoracic-mobility exercises.Occupational therapy consisted of stress management, adviceon energy conservation, and work advice. Patients were contactedby telephone regularly by their physiotherapists for assessmentand to encourage adherence to the rehabilitation program.
After rehabilitation the patients were reassessed by the trialphysicians. Those wishing to proceed were assessed by a surgeon,together with a physician and a physiotherapist, to confirmtheir suitability for surgery and were then randomly assignedto surgery or to continued medical treatment. Both groups werereassessed 3, 6, and 12 months after randomization and at yearlyintervals thereafter. The patients assigned to medical treatmentwere told that they would be offered surgery if the trial showeda significant benefit of surgery after the interim or finalanalysis. An independent data-monitoring committee was set upto conduct the interim analysis and advise on the subsequentconduct of the trial.
Five of the first 15 patients (3 assigned to surgery and 2 tomedical treatment) died early in the trial. These patients hadcarbon monoxide gas-transfer values less than 30 percent ofthe predicted value or shuttle-walking distances of less than150 m (see below), whereas survivors had higher values. Theentry criteria were subsequently modified to exclude patientswith these low values for carbon monoxide gas transfer or walkingdistance.
Initial Assessment and Follow-Up
The patients were interviewed and examined to evaluate theirmobility, general health, smoking status, and willingness toparticipate. Pulmonary-function testing consisted of measurementsof FEV1, forced vital capacity, single-breath carbon monoxidegas transfer, arterial-blood gases, total lung capacity, residualvolume (by whole-body plethysmography), and maximal inspiratoryand expiratory mouth pressures. Exercise tolerance was assessedby the shuttle-walking test, as validated by use in patientswith chronic lung disease.13 This test measures the distancewalked on a level surface when the patient is asked to walkat set speeds that increase after each 10 m.
Imaging consisted of chest radiography and CT scanning (withan electron-beam scanner; Imatron, South San Francisco, Calif.),including inspiratory and expiratory thin sections and contiguous10-mm sections at full inspiration.
Echocardiography, electrocardiography, thallium scanning, andstandard biochemical and hematologic tests were performed inall subjects. Smoking status at enrollment and at randomizationwas tested by measurement of urinary cotinine. Quality of lifewas assessed with use of the 36-item Short-Form Health-RelatedQuestionnaire (SF-36), in which the score ranges from 0 (indicatinglow quality) to 100 (indicating high quality).14
Lung function, shuttle-walking distance, and quality of lifewere assessed 3, 6, 12, and 24 months after randomization tomedical or surgical treatment.
Outcome Measures
The primary outcome measures were mortality and changes in FEV1,shuttle-walking distance, and quality of life at six months.The secondary outcome measures were: changes in forced vitalcapacity, total lung capacity, residual volume, inspiratoryand expiratory mouth pressures, and arterial-blood gas values.
Surgery
Bilateral lung resection was performed through median sternotomyor by thoracoscopy. Lung resection was performed with the useof various mechanical staplers, with or without bovine-pericardial-stripreinforcement. The site and extent of resection were decidedon the basis of CT scanning, together with the findings at surgery.Air leaks were prevented by the use of Tisseal (human fibringlue), if required. Pleurodesis was not performed, but a pleuraltent was fashioned to minimize air leak. Anesthesia was inducedand maintained with propofol, and a lumbar or thoracic epiduralinfusion of diacetylmorphine was instituted. The patient underwentextubation immediately after recovering consciousness at theend of the procedure, with permissive hypercapnia during artificialventilation. Postoperative analgesia was maintained with theepidural infusion. Standard prophylactic treatment includedantibiotics and subcutaneous low-molecular-weight heparin.
Statistical Analysis
Statistical calculations based on a mean (±SD) FEV1 of0.9± 0.4 liter showed that 50 patients would be requiredto demonstrate a 30 percent difference after six months witha power of 90 percent (with a type I error of 0.05) in a between-groupcomparison.13 An independent institute (Clinical Trials Unit,Institute of Cancer Research, England) performed the randomization.The patients were stratified according to their FEV1 values(at least 0.75 liter or less than 0.75 liter) and the presenceor absence of 1-antitrypsin deficiency as determined by serumimmunoturbidometry.
Categorical variables were analyzed by Fisher's exact test.15Comparisons between the two groups were performed by the Wilcoxonrank-sum test.15 We tested whether changes from base line weresignificantly different from zero within each group by usingthe Wilcoxon matched-pairs signed-rank test.15 Mortality ratesin the two groups were compared with use of life-table analysiswith a log-rank test. Relative risks of death at all time pointswere obtained with use of Cox's regression model. The vitalstatus of each patient through the end of May 1999 was ascertained.Analyses were performed with the statistical software packagesSAS and Stata. The results are shown for all patients unlessotherwise specified and are expressed as median values withinterquartile ranges. All reported P values are for two-sidedtests. The trial was approved and monitored by the Royal BromptonHospital research ethics committee, and all patients gave writteninformed consent.
Results
Recruitment
One hundred seventy-four patients were referred, and 48 wererandomly assigned to treatment, 24 to each group. The reasonsfor exclusion were low results on tests of lung function orwalking distance (78 patients), reluctance to take part in thestudy (32 patients), other lung disease (8 patients), continuedsmoking (5 patients), and geographic or other reasons (3 patients).After randomization, one patient in the surgical group withdrewfrom the trial before surgery. The base-line characteristicsof the patients, including the distribution of emphysema onCT, did not differ significantly between the groups (Table 1).Six patients in the medical group (25 percent) and seven inthe surgical group (29 percent) were women. The median age was60 years (interquartile range, 53 to 69) for medically treatedpatients and 62 years (interquartile range, 56 to 67) for surgicallytreated patients. Among the medically treated patients, thedistribution of emphysema according to CT scanning was generalizedin 12 patients, predominantly in the upper zone in 9, and predominantlyin the lower zone in 3. Among the surgically treated patients,the corresponding numbers were 14, 8, and 2 patients.
Table 1. Outcome Measures at Base Line and after Lung-Volume–Reduction Surgery or Continued Medical Treatment.
Primary Outcomes
There were five deaths in the surgical group (21 percent) andthree in the medical group (12 percent). The operative mortality(in-hospital deaths after surgery) was 6 percent (1 of 18) amongthose who met the modified criteria and 17 percent (4 of 23)overall, not including the patient who withdrew after assignmentto surgery. The early deaths in the surgical group (on days2, 11, 15, and 74 after surgery) were due to respiratory failure,with or without infection. One other surgically treated patientdied suddenly at home 287 days after surgery. Deaths in themedical group (on days 72, 242, and 475 after randomization)were due to respiratory failure. Analysis of the entire studygroup showed no significant difference in survival between groups(relative risk of death in the surgical as compared with themedical group, 1.74; 95 percent confidence interval, 0.47 to6.46; P=0.29, by the log-rank test).
The median changes in FEV1, shuttle-walking distance, and SF-36scores from base line to months 3, 6, and 12 are shown in Figure 1and Figure 2. These changes were calculated for patients whohad both sets of measures (i.e., for survivors at each timepoint) and are therefore not identical to the values shown inTable 1. The values improved in the surgical group and tendedto worsen in the medical group. The changes from base line differedsignificantly between the medical and surgical groups at 6 monthsfor FEV1 (–80 ml and +70 ml, respectively; P=0.02), shuttle-walkingdistance (–20 m and +50 m, P=0.02), and SF-36 scores (–12and +22, P=0.003); for FEV1 at 3 months; and for shuttle-walkingdistance and SF-36 score at 12 months.
Figure 1. Median Changes in Forced Expiratory Volume in One Second and Forced Vital Capacity in the Groups Receiving Surgical and Medical Treatment.
The median changes were obtained by comparing the responses of each subject with his or her base-line values, and they therefore differ from the values shown in Table 1. P values are for the comparison between the two groups at each time point. I bars show 95 percent confidence intervals.
Figure 2. Median Changes in Shuttle-Walking Distance and Score on the 36-Item Short-Form Questionnaire (SF-36) Measuring Quality of Life in the Groups Receiving Surgical and Medical Treatment.
The median changes were obtained by comparing the responses of each subject with his or her base-line values, and they therefore differ from the values shown in Table 1. P values are for the comparison between the two groups at each time point. The SF-36 score ranges from 0 (indicating a low quality of life) to 100 (indicating a high quality of life). I bars show 95 percent confidence intervals.
Secondary Outcomes
The median changes in forced vital capacity, percentage of predictedtotal lung capacity, and percentage of predicted residual volumefrom base line to months 3, 6, and 12 are shown in Figure 1and Figure 3. These changes were calculated for patients whohad both sets of measures (i.e., for survivors at each timepoint) and are therefore not identical to the values shown inTable 1. All differences between the surgical and the medicalgroups were significant, except that forced vital capacity didnot differ significantly between the groups at three months.The value for inspiratory mouth pressure, a measure of diaphragmfunction, increased in the surgical group and decreased in themedical group. There were no other significant changes in secondaryoutcomes.
Figure 3. Median Absolute Changes in Residual Volume and Total Lung Capacity, as a Percentage of the Predicted Value, in the Groups Receiving Surgical and Medical Treatment.
The median changes were obtained by comparing the responses of each subject with his or her base-line values, and they therefore differ from the values shown in Table 1. P values are for the comparison between the two groups at each time point. I bars show 95 percent confidence intervals.
Five of the 19 surviving surgically treated patients had nobenefit after surgery. None of the patients resumed smoking.These patients had base-line characteristics similar to thoseof the patients who showed improvement after surgery, exceptthat their emphysema was more diffusely distributed accordingto CT scanning. In the surgical group, the mean hospital staywas 19 days (range, 8 to 64). Postoperative complications includedpersistent air leak in three patients and infection in two patients.
After analysis of the results, the 21 patients in the medicalgroup who completed at least six months of the trial were reassessed.Eight no longer met the criteria for surgery because of a declinein lung function, five no longer wanted to be considered forsurgery, and eight were offered surgery. Six underwent surgery.All six patients were alive 3 to 10 months after surgery. FEV1improved by a mean of 0.27 liter; two of the six patients hadno clinical benefit.
Discussion
In a randomized, controlled trial, we found statistically significantbenefits in terms of FEV1, shuttle-walking distance, and qualityof life at various follow-up times. Mortality was similar inthe two groups, but the study had too few patients for us toevaluate this end point adequately. Although most patients whounderwent surgery had considerable benefit, a few did not. Incontrast, the condition of most of the patients treated medicallygot worse. We therefore consider these changes to be clinicallysignificant for the surgical group as a whole.
A review of 722 patients who underwent lung-volume–reductionsurgery between October 1995 and January 1996 showed that 12months after surgery, 23 percent had died.12 Our results aresimilar. Nevertheless, the mortality early in our trial wasunacceptably high, and therefore the entry criteria were modified.These early operative deaths may have been in part attributableto the inexperience of the surgical team as well as to the severityof the patients' emphysema.
The rate of decline in lung function after randomization wassimilar in the two groups, with a yearly decrease of 100 mlin FEV1. This result suggests that surgery produced a one-timebenefit but did not modify the subsequent natural history ofthe disease. The rate of decline in our patients was higherthan the average for ex-smokers with chronic obstructive pulmonarydisease but similar to that reported in another study of lung-volume–reductionsurgery.12 This is not surprising, given the fact that moreseverely affected patients are selected for the operation.
The chief weaknesses of this study were the small number ofpatients enrolled and the need to modify the entry criteriaafter the first 15 patients had undergone randomization. Thenumber of patients was limited for two reasons. First, therewas reluctance on the part of referring physicians and patientsalike to be subjected to the uncertainty of randomization, particularlyin the face of reports about the benefits of surgery. Many patientsrefused to participate, and some arranged to have surgery elsewhere.Second, all patients were told at entry that they would be offeredthe operation if the trial showed positive results. We thereforeconducted an interim analysis and allowed patients assignedto medical treatment to proceed to surgery.
Although some centers have reported no deaths at all after lung-volume–reductionsurgery, and others have had good results even in the most severelyaffected patients, the 6 percent mortality among our patientswho met the modified entry criteria is in line with generalexperience. The reductions in total lung capacity and residualvolume are also similar to those in other studies, whereas thechanges in FEV1 (an increase of 17.6 percent at three monthsand 9.5 percent at six months) are at the lower end of reportedbenefits. This is likely to reflect in part our rigid exclusionof patients with isolated bullae, for whom surgery has a well-establishedrole. The inclusion of such patients in previous reports mayaccount for the more remarkable successes of up to 80 percentimprovement in FEV1. During the period of this trial, sevenpatients with localized bullae underwent bullectomy at our institution(outside the trial); their mean FEV1 rose from 1.22 to 1.98liters (an increase of 62 percent). The substantial improvementsin walking distance (19 percent at three months, and 24 percentat six months) and quality of life are similar to those foundby others. They are probably due to changes in both lung anddiaphragmatic function, but we recognize that the placebo effectof surgery may have played a part.
Our randomized, controlled trial has confirmed the benefitsof lung-volume–reduction surgery that were suggested byother studies.16,17 Although only a small proportion of patientswith chronic obstructive pulmonary disease may benefit fromthe surgery, their number may be large. The selection criterianeed to be improved before the operation becomes routine.
Supported by research funding from the Royal Brompton Hospital.
We are indebted to Julia Bott for help in the design of thestudy.
Source Information
From the Departments of Respiratory Medicine (D.G., M.D., H.K., P.A., P.C., S.J.M.), Radiology (D.H.), and Thoracic Surgery (U.P., J.P., P.G.), Royal Brompton Hospital, London.
Address reprint requests to Professor Geddes at the Royal Brompton Hospital, London SW3 6LR, United Kingdom.
References
Russi EW, Weder W. Surgical lung volume reduction for severe pulmonary emphysema -- a new review series. Eur Respir J 1999;13:480-481. [Medline]
Cooper JD, Patterson GA, Sundaresan RS, et al. Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema. J Thorac Cardiovasc Surg 1996;112:1319-1330. [Free Full Text]
Kotloff RM, Tino G, Bavaria JE, et al. Bilateral lung volume reduction surgery for advanced emphysema: a comparison of median sternotomy and thoracoscopic approaches. Chest 1996;110:1399-1406. [Free Full Text]
McKenna RJ Jr, Brenner M, Gelb AF, et al. A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. J Thorac Cardiovasc Surg 1996;111:317-322. [Free Full Text]
Russi EW, Stammberger U, Weder W. Lung volume reduction surgery for emphysema. Eur Respir J 1997;10:208-218. [Abstract]
Argenziano M, Thomashow B, Jellen PA, et al. Functional comparison of unilateral versus bilateral lung volume reduction surgery. Ann Thorac Surg 1997;64:321-327. [Free Full Text]
Szekely LA, Oelberg DA, Wright C, et al. Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery. Chest 1997;111:550-558. [Free Full Text]
Sciurba FC. Early and long-term functional outcomes following lung volume reduction surgery. Clin Chest Med 1997;18:259-276. [CrossRef][Medline]
Fein AM, Branman SS, Casaburi R, et al. Lung volume reduction surgery: this official statement of the American Thoracic Society was adopted by the ATS board of directors, May 1996. Am J Respir Crit Care Med 1996;154:1151-1152. [Medline]
Weinmann GG, Hyatt R. Evaluation and research in lung volume reduction surgery. Am J Respir Crit Care Med 1996;154:1913-1918. [Medline]
Lomas DA, Caine N, Wells FC. Health technology assessment: time for a randomised controlled trial of the role of lung volume reduction surgery in the treatment of emphysema. Thorax 1997;52:755-756. [Medline]
Fessler HE, Wise RA. Lung volume reduction surgery: is less really more? Am J Respir Crit Care Med 1999;159:1031-1035. [Free Full Text]
Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax 1992;47:1019-1024. [Free Full Text]
Mahler DA, Mackowiak JI. Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with COPD. Chest 1995;107:1585-1589. [Free Full Text]
Altman DG. Practical statistics for medical research. London: Chapman & Hall, 1991.
Meyers BF, Yusen RD, Lefrak SS, et al. Outcome of Medicare patients with emphysema selected for, but denied, a lung volume reduction operation. Ann Thorac Surg 1998;66:331-336. [Free Full Text]
Wilkens H, Demertzis S, Schäfers H-J, Sybrecht GW. Lung volume reduction surgery compared to conservative treatment in patients with severe emphysema. Am J Respir Crit Care Med 1999;159:Suppl:A926-A926.abstract
Snell, G. I., Hopkins, P., Westall, G., Holsworth, L., Carle, A., Williams, T. J.
(2009). A Feasibility and Safety Study of Bronchoscopic Thermal Vapor Ablation: A Novel Emphysema Therapy. Ann. Thorac. Surg.
88: 1993-1998
[Abstract][Full Text]
Criner, G. J., Belt, P., Sternberg, A. L., Mosenifar, Z., Make, B. J., Utz, J. P., Sciurba, F., for the National Emphysema Treatment Trial Researc,
(2009). Effects of Lung Volume Reduction Surgery on Gas Exchange and Breathing Pattern During Maximum Exercise. Chest
135: 1268-1279
[Abstract][Full Text]
Chan, K. M., Martinez, F. J., Chang, A. C.
(2009). Nonmedical Therapy for Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc
6: 137-145
[Abstract][Full Text]
Weder, W., Tutic, M., Lardinois, D., Jungraithmayr, W., Hillinger, S., Russi, E. W., Bloch, K. E.
(2009). Persistent Benefit From Lung Volume Reduction Surgery in Patients With Homogeneous Emphysema. Ann. Thorac. Surg.
87: 229-237
[Abstract][Full Text]
Moser, C., Opitz, I., Zhai, W., Rousson, V., Russi, E.W., Weder, W., Lardinois, D.
(2008). Autologous fibrin sealant reduces the incidence of prolonged air leak and duration of chest tube drainage after lung volume reduction surgery: a prospective randomized blinded study.. J. Thorac. Cardiovasc. Surg.
136: 843-849
[Abstract][Full Text]
Snyder, M. L., Goss, C. H., Neradilek, B., Polissar, N. L., Mosenifar, Z., Wise, R. A., Fishman, A. P., Benditt, J. O., for the National Emphysema Treatment Trial Researc,
(2008). Changes in Arterial Oxygenation and Self-Reported Oxygen Use after Lung Volume Reduction Surgery. Am. J. Respir. Crit. Care Med.
178: 339-345
[Abstract][Full Text]
Clini, E. M., Ambrosino, N.
(2008). Nonpharmacological treatment and relief of symptoms in COPD. Eur Respir J
32: 218-228
[Abstract][Full Text]
Celli, B. R.
(2008). Update on the Management of COPD. Chest
133: 1451-1462
[Abstract][Full Text]
Ramsey, S. D., Sullivan, S. D., Kaplan, R. M.
(2008). Cost-Effectiveness of Lung Volume Reduction Surgery. Proc Am Thorac Soc
5: 406-411
[Abstract][Full Text]
Brister, N. W., Barnette, R. E., Kim, V., Keresztury, M.
(2008). Anesthetic Considerations in Candidates for Lung Volume Reduction Surgery. Proc Am Thorac Soc
5: 432-437
[Abstract][Full Text]
DeCamp, M. M. Jr., McKenna, R. J. Jr., Deschamps, C. C., Krasna, M. J.
(2008). Lung Volume Reduction Surgery: Technique, Operative Mortality, and Morbidity. Proc Am Thorac Soc
5: 442-446
[Abstract][Full Text]
Ingenito, E. P., Wood, D. E., Utz, J. P.
(2008). Bronchoscopic Lung Volume Reduction in Severe Emphysema. Proc Am Thorac Soc
5: 454-460
[Abstract][Full Text]
Cazzola, M., MacNee, W., Martinez, F. J., Rabe, K. F., Franciosi, L. G., Barnes, P. J., Brusasco, V., Burge, P. S., Calverley, P. M. A., Celli, B. R., Jones, P. W., Mahler, D. A., Make, B., Miravitlles, M., Page, C. P., Palange, P., Parr, D., Pistolesi, M., Rennard, S. I., Rutten-van Molken, M. P., Stockley, R., Sullivan, S. D., Wedzicha, J. A., Wouters, E. F., on behalf of the American Thoracic Society/Europea,
(2008). Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J
31: 416-469
[Abstract][Full Text]
Palange, P., Ward, S. A., Carlsen, K-H., Casaburi, R., Gallagher, C. G., Gosselink, R., O'Donnell, D. E., Puente-Maestu, L., Schols, A. M., Singh, S., Whipp, B. J.
(2007). Recommendations on the use of exercise testing in clinical practice. Eur Respir J
29: 185-209
[Abstract][Full Text]
Wood, D. E., McKenna, R. J. Jr, Yusen, R. D., Sterman, D. H., Ost, D. E., Springmeyer, S. C., Gonzalez, H. X., Mulligan, M. S., Gildea, T., Houck, W. V., Machuzak, M., Mehta, A. C.
(2007). A multicenter trial of an intrabronchial valve for treatment of severe emphysema. J. Thorac. Cardiovasc. Surg.
133: 65-73
[Abstract][Full Text]
Polkey, M. I.
(2006). Surgical procedures in emphysema: any impact on dynamic hyperinflation?. ERR
15: 96-99
[Abstract][Full Text]
Polkey, M. I., Hopkinson, N. S.
(2006). Bronchoscopic lung volume reduction. ERR
15: 99-103
[Abstract][Full Text]
Moore, A. J., Stubbings, A., Swallow, E. B., Dusmet, M., Goldstraw, P., Porcher, R., Moxham, J., Polkey, M. I., Ferenczi, M. A.
(2006). Passive properties of the diaphragm in COPD. J. Appl. Physiol.
101: 1400-1405
[Abstract][Full Text]
Mineo, T. C., Pompeo, E., Mineo, D., Ambrogi, V., Ciarapica, D., Polito, A.
(2006). Resting energy expenditure and metabolic changes after lung volume reduction surgery for emphysema.. Ann. Thorac. Surg.
82: 1205-1211
[Abstract][Full Text]
Naunheim, K. S., Wood, D. E., Mohsenifar, Z., Sternberg, A. L., Criner, G. J., DeCamp, M. M., Deschamps, C. C., Martinez, F. J., Sciurba, F. C., Tonascia, J., Fishman, A. P.
(2006). Long-Term Follow-Up of Patients Receiving Lung-Volume-Reduction Surgery Versus Medical Therapy for Severe Emphysema by the National Emphysema Treatment Trial Research Group. Ann. Thorac. Surg.
82: 431-443
[Abstract][Full Text]
Tutic, M., Lardinois, D., Imfeld, S., Korom, S., Boehler, A., Speich, R., Bloch, K. E., Russi, E. W., Weder, W.
(2006). Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation.. Ann. Thorac. Surg.
82: 208-213
[Abstract][Full Text]
Higuchi, T, Reed, A, Oto, T, Holsworth, L, Ellis, S, Bailey, M J, Williams, T J, Snell, G I
(2006). Relation of interlobar collaterals to radiological heterogeneity in severe emphysema. Thorax
61: 409-413
[Abstract][Full Text]
Lopez, A. D., Shibuya, K., Rao, C., Mathers, C. D., Hansell, A. L., Held, L. S., Schmid, V., Buist, S.
(2006). Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J
27: 397-412
[Full Text]
Naunheim, K. S., Wood, D. E., Krasna, M. J., DeCamp, M. M. Jr, Ginsburg, M. E., McKenna, R. J. Jr, Criner, G. J., Hoffman, E. A., Sternberg, A. L., Deschamps, C., National Emphysema Treatment Trial Research Group,
(2006). Predictors of operative mortality and cardiopulmonary morbidity in the National Emphysema Treatment Trial. J. Thorac. Cardiovasc. Surg.
131: 43-53
[Abstract][Full Text]
Miller, J. D., Malthaner, R. A., Goldsmith, C. H., Goeree, R., Higgins, D., Cox, P. G., Tan, L., Road, J. D., Canadian Lung Volume Reduction Surgery Study,
(2006). A Randomized Clinical Trial of Lung Volume Reduction Surgery Versus Best Medical Care for Patients With Advanced Emphysema: A Two-Year Study From Canada. Ann. Thorac. Surg.
81: 314-321
[Abstract][Full Text]
Celli, B. R.
(2006). Chronic Obstructive Pulmonary Disease: From Unjustified Nihilism to Evidence-based Optimism.. Proc Am Thorac Soc
3: 58-65
[Abstract][Full Text]
Krachman, S. L., Chatila, W., Martin, U. J., Nugent, T., Crocetti, J., Gaughan, J., Criner, G. J., for the National Emphysema Treatment Trial Researc,
(2005). Effects of Lung Volume Reduction Surgery on Sleep Quality and Nocturnal Gas Exchange in Patients With Severe Emphysema. Chest
128: 3221-3228
[Abstract][Full Text]
Hillerdal, G., Lofdahl, C.-G., Strom, K., Skoogh, B.-E., Jorfeldt, L., Nilsson, F., Forslund-Stiby, D., Ranstam, J., Gyllstedt, E., of the Swedish VOLREM Group,
(2005). Comparison of Lung Volume Reduction Surgery and Physical Training on Health Status and Physiologic Outcomes: A Randomized Controlled Clinical Trial. Chest
128: 3489-3499
[Abstract][Full Text]
Barnes, P. J., Stockley, R. A.
(2005). COPD: current therapeutic interventions and future approaches. Eur Respir J
25: 1084-1106
[Abstract][Full Text]
Mineo, T. C., Ambrogi, V., Mineo, D., Fabbri, A., Fabbrini, E., Massoud, R.
(2005). Bone Mineral Density Improvement After Lung Volume Reduction Surgery for Severe Emphysema. Chest
127: 1960-1966
[Abstract][Full Text]
McKeoughl, Z J, Alison, J A, Bayfield, M S, Bye, P T.P
(2005). Supported and unsupported arm exercise capacity following lung volume reduction surgery: a pilot study. Chronic Respiratory Disease
2: 59-65
[Abstract]
Yusen, R. D., Littenberg, B.
(2005). Integrating Survival and Quality of Life Data in Clinical Trials of Lung Disease: The Case of Lung Volume Reduction Surgery. Chest
127: 1094-1096
[Full Text]
Miller, J. D., Berger, R. L., Malthaner, R. A., Celli, B. R., Goldsmith, C. H., Ingenito, E. P., Higgins, D., Bagley, P., Cox, G., Wright, C. D.
(2005). Lung Volume Reduction Surgery vs Medical Treatment: For Patients With Advanced Emphysema. Chest
127: 1166-1177
[Abstract][Full Text]
Hopkinson, N. S., Toma, T. P., Hansell, D. M., Goldstraw, P., Moxham, J., Geddes, D. M., Polkey, M. I.
(2005). Effect of Bronchoscopic Lung Volume Reduction on Dynamic Hyperinflation and Exercise in Emphysema. Am. J. Respir. Crit. Care Med.
171: 453-460
[Abstract][Full Text]
Hillier, J. E., Toma, T. P., Gillbe, C. E.
(2004). Bronchoscopic Lung Volume Reduction in Patients with Severe Emphysema: Anesthetic Management. Anesth. Analg.
99: 1610-1614
[Abstract][Full Text]
Tutic, M., Bloch, K. E., Lardinois, D., Brack, T., Russi, E. W., Weder, W.
(2004). Long-term results after lung volume reduction surgery in patients with {alpha}1-antitrypsin deficiency. J. Thorac. Cardiovasc. Surg.
128: 408-413
[Abstract][Full Text]
Ost, D., Glassman, L., Fein, A. M., Marcus, P.
(2004). Innovations in Lung Volume Reduction: The Non-Cutting Edge. Chest
126: 6-9
[Full Text]
Sutherland, E. R., Cherniack, R. M.
(2004). Management of Chronic Obstructive Pulmonary Disease. NEJM
350: 2689-2697
[Full Text]
Lee, S. M, Wise, R., Sternberg, A. L, Tonascia, J., Piantadosi, S., National Emphysema Treatment Trial Research Group,
(2004). Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial. Clin Trials
1: 326-338
[Abstract]
Laghi, F., Jubran, A., Topeli, A., Fahey, P. J., Garrity, E. R. Jr, de Pinto, D. J., Tobin, M. J.
(2004). Effect of Lung Volume Reduction Surgery on Diaphragmatic Neuromechanical Coupling At 2 Years. Chest
125: 2188-2195
[Abstract][Full Text]
Meyers, B. F., Yusen, R. D., Guthrie, T. J., Patterson, G. A., Lefrak, S. S., Davis, G. E., Cooper, J. D.
(2004). Results of lung volume reduction surgery in patients meeting a National Emphysema Treatment Trial high-risk criterion. J. Thorac. Cardiovasc. Surg.
127: 829-835
[Abstract][Full Text]
Dolmage, T.E., Waddell, T.K., Maltais, F., Guyatt, G.H., Todd, T.R.J., Keshavjee, S., van Rooy, S., Krip, B., LeBlanc, P., Goldstein, R.S.
(2004). The influence of lung volume reduction surgery on exercise in patients with COPD. Eur Respir J
23: 269-274
[Abstract][Full Text]
Mineo, T.C., Ambrogi, V., Pompeo, E., Elia, S., Mineo, D., Bollero, P., Nofroni, I.
(2004). Impact of lung volume reduction surgery versus rehabilitation on quality of life. Eur Respir J
23: 275-280
[Abstract][Full Text]
Mink, S. N., Gonzalez, X., Duke, K., Bautista, E., Tan, L.
(2004). Lung Volume Reduction Surgery in Canine Model of Predominantly Upper Lobe Emphysema: Advantages of New Surgical System. Chest
125: 633-643
[Abstract][Full Text]
Maxfield, R. A.
(2004). New and Emerging Minimally Invasive Techniques for Lung Volume Reduction. Chest
125: 777-783
[Abstract][Full Text]
Lomas, D A
(2004). Lung volume reduction surgery: where are we now?. Chronic Respiratory Disease
1: 2-4
Chatila, W. M., Wynkoop, W. A., Vance, G., Criner, G. J.
(2004). Smoking Patterns in African Americans and Whites With Advanced COPD. Chest
125: 15-21
[Abstract][Full Text]
Celli, B. R.
(2003). A 62-Year-Old Woman With Chronic Obstructive Pulmonary Disease. JAMA
290: 2721-2729
[Full Text]
Decramer, M.
(2003). Treatment of chronic respiratory failure: lung volume reduction surgery versus rehabilitation. Eur Respir J
22: 47s-56s
[Abstract][Full Text]
Sin, D. D., McAlister, F. A., Man, S. F. P., Anthonisen, N. R.
(2003). Contemporary Management of Chronic Obstructive Pulmonary Disease: Scientific Review. JAMA
290: 2301-2312
[Abstract][Full Text]
Jorgensen, K., Houltz, E., Westfelt, U., Nilsson, F., Schersten, H., Ricksten, S.-E.
(2003). Effects of Lung Volume Reduction Surgery on Left Ventricular Diastolic Filling and Dimensions in Patients With Severe Emphysema. Chest
124: 1863-1870
[Abstract][Full Text]
Russi, E.W., Bloch, K.E., Weder, W.
(2003). Lung volume reduction surgery: what can we learn from the National Emphysema Treatment Trial?. Eur Respir J
22: 571-573
[Full Text]
Oey, I. F., Morgan, M. D.L., Singh, S. J., Spyt, T. J., Waller, D. A.
(2003). The long-term health status improvements seen after lung volume reduction surgery. Eur. J. Cardiothorac. Surg.
24: 614-619
[Abstract][Full Text]
Munro, P. E., Bailey, M. J., Smith, J. A., Snell, G. I.
(2003). Lung Volume Reduction Surgery in Australia and New Zealand: Six Years On: Registry Report. Chest
124: 1443-1450
[Abstract][Full Text]
Snell, G. I., Holsworth, L., Borrill, Z. L., Thomson, K. R., Kalff, V., Smith, J. A., Williams, T. J.
(2003). The Potential for Bronchoscopic Lung Volume Reduction Using Bronchial Prostheses: A Pilot Study. Chest
124: 1073-1080
[Abstract][Full Text]
Calverley, P M A
(2003). Closing the NETT on lung volume reduction surgery. Thorax
58: 651-653
[Full Text]
Laghi, F., Tobin, M. J.
(2003). Disorders of the Respiratory Muscles. Am. J. Respir. Crit. Care Med.
168: 10-48
[Abstract][Full Text]
Wijkstra, P. J., Lacasse, Y., Guyatt, G. H., Casanova, C., Gay, P. C., Meecham Jones, J., Goldstein, R. S.
(2003). A Meta-analysis of Nocturnal Noninvasive Positive Pressure Ventilation in Patients With Stable COPD. Chest
124: 337-343
[Abstract][Full Text]
Meyers, B F, Patterson, G A
(2003). Chronic obstructive pulmonary disease * 10: Bullectomy, lung volume reduction surgery, and transplantation for patients with chronic obstructive pulmonary disease. Thorax
58: 634-638
[Abstract][Full Text]
Appleton, S., Adams, R., Porter, S., Peacock, M., Ruffin, R.
(2003). Sustained Improvements in Dyspnea and Pulmonary Function 3 to 5 Years After Lung Volume Reduction Surgery. Chest
123: 1838-1846
[Abstract][Full Text]
Takayama, T., Shindoh, C., Kurokawa, Y., Hida, W., Kurosawa, H., Ogawa, H., Satomi, S.
(2003). Effects of Lung Volume Reduction Surgery for Emphysema on Oxygen Cost of Breathing. Chest
123: 1847-1852
[Abstract][Full Text]
National Emphysema Treatment Trial Research Group,
(2003). A Randomized Trial Comparing Lung-Volume-Reduction Surgery with Medical Therapy for Severe Emphysema. NEJM
348: 2059-2073
[Abstract][Full Text]
National Emphysema Treatment Trial Research Group,
(2003). Cost Effectiveness of Lung-Volume-Reduction Surgery for Patients with Severe Emphysema. NEJM
348: 2092-2102
[Abstract][Full Text]
Drazen, J. M., Epstein, A. M.
(2003). Guidance Concerning Surgery for Emphysema. NEJM
348: 2134-2136
[Full Text]
Goldstein, R S, Todd, T R J, Guyatt, G, Keshavjee, S, Dolmage, T E, van Rooy, S, Krip, B, Maltais, F, LeBlanc, P, Pakhale, S, Waddell, T K
(2003). Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease. Thorax
58: 405-410
[Abstract][Full Text]
Yusen, R. D., Lefrak, S. S., Gierada, D. S., Davis, G. E., Meyers, B. F., Patterson, G. A., Cooper, J. D.
(2003). A Prospective Evaluation of Lung Volume Reduction Surgery in 200 Consecutive Patients. Chest
123: 1026-1037
[Abstract][Full Text]
Ciccone, A. M., Meyers, B. F., Guthrie, T. J., Davis, G. E., Yusen, R. D., Lefrak, S. S., Patterson, G. A., Cooper, J. D.
(2003). Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema. J. Thorac. Cardiovasc. Surg.
125: 513-525
[Abstract][Full Text]
MacNee, W, Calverley, P M A
(2003). Chronic obstructive pulmonary disease * 7: Management of COPD. Thorax
58: 261-265
[Abstract][Full Text]
Ingenito, E. P., Berger, R. L., Henderson, A. C., Reilly, J. J., Tsai, L., Hoffman, A.
(2003). Bronchoscopic Lung Volume Reduction Using Tissue Engineering Principles. Am. J. Respir. Crit. Care Med.
167: 771-778
[Abstract][Full Text]
Ingenito, E. P., Loring, S. H., Moy, M. L., Mentzer, S. J., Swanson, S. J., Reilly, J. J.
(2003). Physiological characterization of variability in response to lung volume reduction surgery. J. Appl. Physiol.
94: 20-30
[Abstract][Full Text]
Beckles, M. A., Spiro, S. G., Colice, G. L., Rudd, R. M.
(2003). The Physiologic Evaluation of Patients With Lung Cancer Being Considered for Resectional Surgery. Chest
123
: 105S-114S
[Abstract][Full Text]
Mineo, T. C., Ambrogi, V., Pompeo, E., Bollero, P., Mineo, D., Nofroni, I.
(2002). Body weight and nutritional changes after reduction pneumoplasty for severe emphysema: A randomized study. J. Thorac. Cardiovasc. Surg.
124: 660-667
[Abstract][Full Text]
Stoica, S. C., Craig, S. R., Soon, S. Y., Walker, W. S.
(2002). Spontaneous rupture of the right hemidiaphragm after video-assisted lung volume reduction operation. Ann. Thorac. Surg.
74: 929-931
[Abstract][Full Text]
Bloch, K. E., Weder, W., Boehler, A., Zalunardo, M. P., Russi, E. W.
(2002). Successful Lung Volume Reduction Surgery in a Child With Severe Airflow Obstruction and Hyperinflation due to Constrictive Bronchiolitis*. Chest
122: 747-750
[Abstract][Full Text]
Bellemare, F., Cordeau, M.-P., Couture, J., Lafontaine, E., Leblanc, P., Passerini, L.
(2002). Effects of Emphysema and Lung Volume Reduction Surgery on Transdiaphragmatic Pressure and Diaphragm Length*. Chest
121: 1898-1910
[Abstract][Full Text]
Bloch, K. E., Georgescu, C. L., Russi, E. W., Weder, W.
(2002). Gain and subsequent loss of lung function after lung volume reduction surgery in cases of severe emphysema with different morphologic patterns. J. Thorac. Cardiovasc. Surg.
123: 845-854
[Abstract][Full Text]
Polkey, M. I.
(2002). Muscle Metabolism and Exercise Tolerance in COPD*. Chest
121
: 131S-135S
[Abstract][Full Text]
Pompeo, E., Mineo, T. C.
(2002). Long-term outcome of staged versus one-stage bilateral thoracoscopic reduction pneumoplasty. Eur. J. Cardiothorac. Surg.
21: 627-633
[Abstract][Full Text]
Marchand, E., De Leyn, P., Gayan-Ramirez, G., Palecek, F., Verbeken, E., Decramer, M.
(2002). Effects of lung volume reduction surgery in hamsters with elastase-induced emphysema. Eur Respir J
19: 422-428
[Abstract][Full Text]
Fujimoto, T., Teschler, H., Hillejan, L., Zaboura, G., Stamatis, G.
(2002). Long-term results of lung volume reduction surgery. Eur. J. Cardiothorac. Surg.
21: 483-488
[Abstract][Full Text]
MINEO, T. C., POMPEO, E., ROGLIANI, P., DAURI, M., TURANI, F., BOLLERO, P., MAGLIOCCHETTI, N.
(2002). Effect of Lung Volume Reduction Surgery for Severe Emphysema on Right Ventricular Function. Am. J. Respir. Crit. Care Med.
165: 489-494
[Abstract][Full Text]
Hamacher, J., Buchi, S., Georgescu, C.L., Stammberger, U., Thurnheer, R., Bloch, K.E., Weder, W., Russi, E.W.
(2002). Improved quality of life after lung volume reduction surgery. Eur Respir J
19: 54-60
[Abstract][Full Text]
FESSLER, H. E., SCHARF, S. M., PERMUTT, S.
(2002). Improvement in Spirometry following Lung Volume Reduction Surgery . Application of a Physiologic Model. Am. J. Respir. Crit. Care Med.
165: 34-40
[Abstract][Full Text]
Toma, T P, Goldstraw, P, Geddes, D M
(2002). Lung volume reduction surgery. Thorax
57: 5-5
[Full Text]
NAKANO, Y., COXSON, H. O., BOSAN, S., ROGERS, R. M., SCIURBA, F. C., KEENAN, R. J., WALLEY, K. R., PARE, P. D., HOGG, J. C.
(2001). Core to Rind Distribution of Severe Emphysema Predicts Outcome of Lung Volume Reduction Surgery. Am. J. Respir. Crit. Care Med.
164: 2195-2199
[Abstract][Full Text]
Kerstjens, H. A M, Groen, H. J, van der Bij, W.
(2001). Recent advances: Respiratory medicine. BMJ
323: 1349-1353
[Full Text]
Kotloff, R. M., Hansen-Flaschen, J., Lipson, D. A., Tino, G., Arcasoy, S. M., Alavi, A., Kaiser, L. R.
(2001). Apical Perfusion Fraction as a Predictor of Short-term Functional Outcome Following Bilateral Lung Volume Reduction Surgery. Chest
120: 1609-1615
[Abstract][Full Text]
British Thoracic Society Standards of Care Subcomm,
(2001). Pulmonary rehabilitation. Thorax
56: 827-834
[Full Text]
National Emphysema Treatment Trial Research Group,
(2001). Patients at High Risk of Death after Lung-Volume-Reduction Surgery. NEJM
345: 1075-1083
[Abstract][Full Text]
Madani, A., Keyzer, C., Gevenois, P.A.
(2001). Quantitative computed tomography assessment of lung structure and function in pulmonary emphysema. Eur Respir J
18: 720-730
[Abstract][Full Text]
Stirling, G. R., Babidge, W. J., Peacock, M. J., Smith, J. A., Matar, K. S., Snell, G. I., Colville, D. J., Maddern, G. J.
(2001). Lung volume reduction surgery in emphysema: a systematic review. Ann. Thorac. Surg.
72: 641-648
[Abstract][Full Text]
Berger, R. L., Celli, B. R., Meneghetti, A. L., Bagley, P. H., Wright, C. D., Ingenito, E. P., Gray, A., Snider, G. L.
(2001). Limitations of randomized clinical trials for evaluating emerging operations: the case of lung volume reduction surgery. Ann. Thorac. Surg.
72: 649-657
[Abstract][Full Text]
Meyers, B. F., Yusen, R. D., Lefrak, S. S., Cooper, J. D.
(2001). Improved long-term survival seen after lung volume reduction surgery compared to continued medical therapy for emphysema. Ann. Thorac. Surg.
71: 2081-2081
[Full Text]
GELB, A. F., McKENNA, R. J. Jr., BRENNER, M., EPSTEIN, J. D., ZAMEL, N.
(2001). Lung Function 5 yr after Lung Volume Reduction Surgery for Emphysema. Am. J. Respir. Crit. Care Med.
163: 1562-1566
[Abstract][Full Text]
Ellis, J R C, Gleeson, F V
(2001). Lung cancer screening. Br. J. Radiol.
74: 478-485
[Abstract][Full Text]
Gelb, A. F., McKenna, R. J. Jr, Brenner, M.
(2001). Expanding Knowledge of Lung Volume Reduction. Chest
119: 1300-1303
[Full Text]
PAUWELS, R. A., BUIST, A. S., CALVERLEY, P. M. A., JENKINS, C. R., HURD, S. S.
(2001). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease . NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary. Am. J. Respir. Crit. Care Med.
163: 1256-1276
[Full Text]
(2000). Randomized Trial of Lung Volume Reduction Surgery. JWatch General
2000: 1-1
[Full Text]
1-antitrypsin deficiency as determined by serum immunoturbidometry. 
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