and services can be found online on the World Wide Web at: The online version of this article, along with updated information
) ISSN:0012-3692http://www.chestjournal.org/site/misc/reprints.xhtml(of the copyright holder.may be reproduced or distributed without the prior written permission Northbrook IL 60062. All rights reserved. No part of this article or PDFby the American College of Chest Physicians, 3300 Dundee Road,
2007Physicians. It has been published monthly since 1935. Copyright CHEST is the official journal of the American College of Chest
The Effects of Pulmonary Rehabilitationin the National Emphysema TreatmentTrial*
Andrew L. Ries, MD, MPH; Barry J. Make, MD; Shing M. Lee, ScM;Mark J. Krasna, MD; Matthew Bartels, MD; Rebecca Crouch, PT; andAlfred P. Fishman, MD; for the National Emphysema Treatment Trial ResearchGroup†
Study objectives: Pulmonary rehabilitation is an established treatment in patients with chroniclung disease but is not widely utilized. Most trials have been conducted in single centers. TheNational Emphysema Treatment Trial (NETT) provided an opportunity to evaluate pulmonaryrehabilitation in a large cohort of patients who were treated in centers throughout the UnitedStates.Design: Prospective observational study of cohort prior to randomization in a multicenter clinicaltrial.Setting: University-based clinical centers and community-based satellite pulmonary rehabilitationprograms.Patients and intervention: A total of 1,218 patients with severe emphysema underwent pulmonaryrehabilitation before and after randomization to lung volume reduction surgery (LVRS) orcontinued medical management. Rehabilitation was conducted at 17 NETT centers supple-mented by 539 satellite centers.Measurements and results: Lung function, exercise tolerance, dyspnea, and quality of life wereevaluated at regular intervals. Significant (p < 0.001) improvements were observed consistentlyin exercise (cycle ergometry, 3.1 W; 6-min walk test distance, 76 feet), dyspnea (University ofCalifornia, San Diego Shortness of Breath Questionnaire score, �3.2; Borg breathlessness score:breathing cycle, �0.8; 6-min walk, �0.5) and quality of life (St. George Respiratory Questionnairescore, �3.5; Quality of Well-Being Scale score, �0.035; Medical Outcomes Study 36-item shortform score: physical health summary, �1.3; mental health summary, � 2.0). Patients who had notundergone prior rehabilitation improved more than those who had. In multivariate models, onlyprior rehabilitation status predicted changes after rehabilitation. In 20% of patients, exerciselevel changed sufficiently after rehabilitation to alter the NETT subgroup predictive of outcome.Overall, changes after rehabilitation did not predict differential mortality or improvement inexercise (primary outcomes) by treatment group.Conclusions: The NETT experience demonstrates the effectiveness of pulmonary rehabilitation inpatients with severe emphysema who were treated in a national cross-section of programs.Pulmonary rehabilitation plays an important role in preparing and selecting patients for surgicalinterventions such as LVRS. (CHEST 2005; 128:3799–3809)
Abbreviations: LVRS � lung volume reduction surgery; NETT � National Emphysema Treatment Trial;QWB � quality of well-being; RV � residual volume; SF-36 � Medical Outcomes Study 36-item short form;TLC � total lung capacity; UCSD � University of California San Diego
P ulmonary rehabilitation enhances standard ther-apy for patients with emphysema by helping to
control and alleviate symptoms, to optimize func-tional capacity, and to reduce the medical andeconomic burdens of disabling lung disease.1–9 Mostclinical trials have been conducted in individualresearch-based centers, whereas the majority of pul-monary rehabilitation services are provided in clini-
cal, community-based programs. The National Em-physema Treatment Trial (NETT), a multicentertrial evaluating lung volume reduction surgery(LVRS) in patients with advanced emphysema, pro-vides a unique opportunity to examine the effective-ness of pulmonary rehabilitation administered in avariety of centers throughout the United States.10,11
In the NETT, all subjects who were eligible after the
initial evaluation completed 6 to 10 weeks of stan-dardized pulmonary rehabilitation prior to random-ization. The rehabilitation program was directly su-pervised by the NETT center where the patient hadenrolled, although portions of the program for somepatients were carried out at a satellite facility certi-fied by the supervising center.10 Although NETT
For editorial comment see page 3783
was not specifically designed to evaluate pulmonaryrehabilitation, it does allow a descriptive analysis ofchanges in health outcomes after pulmonary rehabil-itation in a large cohort of patients who are widelydistributed across the United States. The purpose ofthis report was to describe these analyses.
Materials and Methods
Study Design, Subjects, and Assessments
The overall design of the NETT and its preliminary resultshave been reported previously.10–13 The 17 participating NETTcenters randomly assigned 1,218 patients with emphysema (meanFEV1, 26.9% predicted) to either undergo LVRS with medicaltherapy or to receive continued medical management alone.11 Allpatients gave written informed consent on forms that had beenapproved by the human subjects committee at each center.
After an initial evaluation to establish preliminary eligibilityand before randomization, all subjects were required to completea comprehensive program of pulmonary rehabilitation regardlessof whether they had undergone pulmonary rehabilitation at anytime previously. Assessments were performed before and afterthis initial phase of rehabilitation. Only after successfully com-pleting rehabilitation were subjects eligible to enter the random-ized portion of the trial.
NETT Pulmonary Rehabilitation Program
The NETT rehabilitation program was designed to optimizephysical and psychosocial function and to improve each patient’sunderstanding of lung disease and his/her ability to manage it.Secondary goals included the provision of detailed information tothe patient about the complex NETT protocol to ensure, asfollows: (1) truly informed consent; (2) bonding with the NETTcenter to optimize continued participation in this difficult, long-term trial; and (3) adherence to recommendations for optimalmedical management. The basic principle of the rehabilitationprogram was a study-directed daily care program with specifiedcenter-based supervised sessions to ensure that all patientsreceived standardized educational and psychosocial treatmentand appropriate adjustment of exercise training. All patients wereexpected to continue their rehabilitation care plans daily at homethroughout the study.
The NETT pulmonary rehabilitation program was divided intothe following three phases: prerandomization; postrandomiza-tion; and long-term maintenance. The prerandomization phaseincluded a total of 16 to 20 supervised sessions that werecompleted over a period of 6 to 10 weeks. The comprehensiveprogram included components of exercise training (ie, lowerextremity, upper extremity, flexibility, and strength), education,psychosocial assessment and treatment, and nutritional assess-ment and treatment. Individual goals were established during aninitial rehabilitation evaluation during screening for the trial. Thefirst four rehabilitation sessions were provided at a NETT center.The remaining 12 to 16 sessions were provided either at the sameNETT center or at a satellite facility nearer to the patient’s homethat had been certified by the NETT center that remainedresponsible for patient management. Individual satellite centerscould be certified by more than one NETT center. The certifyingNETT center was responsible for ensuring that satellite centerstaff members were trained in NETT procedures and for over-seeing the patient’s rehabilitation program through regular com-munication including weekly progress reports and exercise ses-sion logs.
Each required session included supervised exercise trainingand either an education or psychosocial session. The exercise-training program incorporated lower extremity endurance exer-cise that was accomplished either by walking or by riding on abicycle (five times per week), supported or unsupported upperextremity exercise (three times per week), flexibility exercises(five times per week), and strength training with latex resistivebands and tubing, free weights, or circuit training (three timesper week). Each NETT center was responsible for developing aspecific exercise-training program consistent with the NETTprotocol and for ensuring compliance in its certified satellitecenters. The education program was tailored to the individualpatient, and covered both disease-specific and study-relatedtopics. Psychosocial assessment was performed by rehabilitationstaff during the initial evaluation, and was supplemented by theBeck Depression Inventory,14,15 the Self-Evaluation Question-naire of state and trait anxiety,16 and the Trail Making Test toassess divided attention and psychomotor functioning.17 Psycho-social counseling was provided by an appropriate mental healthprofessional. Patients with serious psychological problems werereferred to a psychologist or psychiatrist. After completingprerandomization pulmonary rehabilitation, each patient wasreevaluated at the NETT center and was allowed to proceed torandomization only after completing this evaluation.
The postrandomization phase included an additional 8 to 9weeks of supervised rehabilitation. LVRS patients began rehabil-itation activities in the hospital as soon as was practical aftersurgery. At the time of hospital discharge, they received aminimum of two rehabilitation sessions at the NETT center
*From the University of California, San Diego (Dr. Ries), SanDiego, CA; National Jewish Medical and Research Center (Dr.Make), Denver, CO; The Johns Hopkins University (Ms. Lee),Baltimore, MD; University of Maryland (Dr. Krasna), Balrimore,MD; Columbia University (Dr. Bartels), New York, NY; DukeUniversity (Ms. Crouch), Durham, NC; and the University ofPennsylvania (Dr. Fishman), Philadelphia, PA.†A complete list of participants and centers in the NETT islocated in the Appendix.The National Emphysema Treatment Trial (NETT) is supportedby contracts with the National Heart, Lung, and Blood Institute(N01HR76101, N01HR76102, N01HR76103, N01HR76104,N01HR76105, N01HR76106, N01HR76107, N01HR76108,N01HR76109, N01HR761010, N01HR761011, N01HR761012,N01HR761013, N01HR761014, N01HR761015, N01HR761016,N01HR76118, and N01HR761019), the Centers for Medicareand Medicaid Services (formerly the Health Care FinancingAdministration), and the Agency for Healthcare Research andQuality.Manuscript received April 16, 2005; revision accepted June 23,2005.Reproduction of this article is prohibited without written permissionfrom the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).Correspondence to: Andrew L. Ries, MD, MPH, UCSD MedicalCenter, 200 W Arbor Dr, No. 8377, San Diego, CA 92103-8377;e-mail: [email protected]
followed by supervised sessions at least once weekly over 8 weeksat either the NETT center or a satellite center. Similar to theprerandomization phase, supervised sessions included reinforce-ment education, and exercise, psychosocial, and nutrition com-ponents. For medical patients, this phase began immediatelyafter randomization. A minimum of two psychosocial sessions wasrequired to assist the patient in overcoming any disappointmentconcerning the assigned treatment arm.
The long-term maintenance phase continued for the durationof follow-up in the NETT. Each NETT center maintainedcontact through scheduled in-person visits that were supple-mented with regular telephone contact to assess adherence to therehabilitation treatment plan. When necessary, additional super-vised rehabilitation sessions could be prescribed.
Statistical Analysis
Measures of physiologic and psychosocial function before andafter rehabilitation were evaluated with descriptive statistics andpaired t tests. In addition to the analysis for all patients, stratifiedanalyses by prior rehabilitation experience and rehabilitationlocation were performed. All p values were based on two-sidedtests and were not corrected for multiple comparisons. A p valueof � 0.05 was considered to be significant. Multivariate analysesof determinants of change after rehabilitation were performed byforward stepwise linear regression. The dependent variablesanalyzed included maximum cycle ergometry workload, mea-sured in watts (a primary outcome measure in the NETT),10,11
total St. George Respiratory Questionnaire score,18 and theUniversity of California, San Diego (UCSD) Shortness of BreathQuestionnaire score.19 The following candidate-independentvariables were selected for univariate analysis: FEV1; inspiratorycapacity; residual volume (RV)/total lung capacity (TLC)ratio;diffusing capacity of the lung for carbon monoxide; cutaneousoxygen saturation on the oxygen titration walk; maximum work-load and perceived symptoms of breathlessness and musclefatigue on the cycle ergometry test; St. George RespiratoryQuestionnaire total and subscale scores; quality of well-being(QWB) score; Medical Outcomes Study 36-item short form(SF-36) subscale and physical and mental component scores;UCSD Shortness of Breath score; prior rehabilitation experience(yes/no); rehabilitation location (NETT center or satellite); andincome level. For the multivariate models, candidate-indepen-dent variables for all analyses included age, gender, NETTcenter, and prerandomization value for the dependent variable inaddition to any of the other independent variables for which theunivariate model p value was � 0.15. Independent variables forthe final multivariate model were then selected as predictive ifthe p value from stepwise forward selection was � 0.05.
In the primary report of the NETT results,11 key subgroupswere identified because of important findings of differentialoutcome by treatment group. Maximum exercise capacity afterrehabilitation and the distribution of emphysema proved to beimportant characteristics in defining these subgroups. Therefore,we examined the impact of pulmonary rehabilitation on subgroupassignment. Patients were categorized into high and low exercisecapacity groups based on the 40th percentile gender-specificvalues that previously had been identified in the NETT (women,25 W; men, 40 W) both before and after pulmonary rehabilita-tion.11 The McNemar test was used to test for the statisticalsignificance of change in subgroup assignment from prerehabili-tation to postrehabilitation. A separate analysis was performed forpatients with and without prior pulmonary rehabilitation.
Additional multivariate analyses were performed to evaluatethe potential effects of changes after pulmonary rehabilitation onpredicting differential mortality and a 10-W change in maximumcycle work (primary outcome measures in NETT) by treatment.
Mortality was analyzed using Cox regression. Improvement, asdefined by a change in the maximum cycle work of � 10 W, wasanalyzed using logistic regression. For these analyses, the inde-pendent variables selected for analysis included changes afterprerandomization pulmonary rehabilitation in maximum work-load, 6-min walk distance, St. George total score, QWB score,and UCSD Shortness of Breath Questionnaire score. The modelfor predicting differential outcome included the independentvariable, the treatment group assignment, and the interactionbetween them. All analyses were performed using a statisticalsoftware package (SAS, version 8.0; SAS Institute; Cary, NC).
Results
Study Patients
A total of 3,777 patients underwent comprehen-sive evaluation at 1 of the 17 participating centers. Ofthese patients, 1,796 met the preliminary eligibilitycriteria and began the prerandomization pulmonaryrehabilitation program. Over the next 10 weeks, 578of these patients did not proceed to randomizationfor a variety of reasons including the following: notcompleting the rehabilitation program or postpro-gram assessment; doing well in rehabilitation andbecoming unwilling to risk surgery; decline in func-tion during rehabilitation and being declared ineli-gible either by choice or by study investigators;making an informed choice not to continue afterfurther discussions during rehabilitation; illness orother complication rendering patients ineligible forsurgery; or exclusion by the surgeon. It should benoted that surgeons had the option to exclude anypatient they were unwilling to operate on at the timeof the preoperative evaluation that was requiredprior to randomization. Additional data were notavailable about these patients who were excludedfrom the study and further follow-up. The analysespresented in this article were based on completeprerandomization and postrandomization data thatwere collected on all patients in the final cohort whosuccessfully completed pulmonary rehabilitation andproceeded to randomization.
Effects of Prerandomization PulmonaryRehabilitation
The characteristics of the 1,218 patients at initialevaluation prior to rehabilitation are presented inTable 1. Of note, 777 patients (64%) had receivedprior pulmonary rehabilitation, and 786 patients(65%) had utilized one of the satellite rehabilitationcenters. As expected, on average, these patients hadsevere airflow obstruction and marked impairmentin exercise capacity, symptoms of dyspnea, andreduction in health-related quality of life. On theoxygen titration test, 58% required supplementaloxygen to maintain saturation levels of � 90% bycutaneous oximetry.
*Values are given as the mean � SD or No. (%). BD � bronchodilator; IC � inspiratory capacity; Dlco � diffusion capacity of the lung forcarbon monoxide. The Borg scale is a 10-point categoric perceived symptom scale in which the patient rates symptoms of breathlessness andmuscle fatigue at the end of the exercise tests; higher scores indicate worse symptoms.
†The St. George Respiratory Questionnaire is a 51-item respiratory disease-specific, health-related, quality-of-life questionnaire that is completedby the patient. The total score ranges from 0 to 100, with lower scores indicating better health-related quality of life.
‡The UCSD Shortness-of-Breath Questionnaire is a 24-item questionnaire about dyspnea with activities of daily living that is completed by thepatient. The total score ranges from 0 to 120, with lower scores indicating less shortness of breath.
§The QWB scale is a 77-item questionnaire that is completed by the patient with regard to general quality of life. The average daily total scoreranges from 0 to 1, where higher scores indicate better quality of life.
�SF 36 is a 36-item questionnaire completed by the patient with regard to general quality of life; scores on the eight subscales range from 0 to100, where higher scores indicate better quality of life. Scores on the physical and mental health summary scores are standardized to the normalUS population with a mean of 50 and an SD of 10, where higher scores indicate better quality of life.
Changes after pulmonary rehabilitation are pre-sented in Table 2 for (1) all patients (n � 1218), (2)patients with prior pulmonary rehabilitation (n � 777)and without prior pulmonary rehabilitation(n � 441), and (3) patients who completed pulmo-nary rehabilitation using a satellite center (n � 786)or solely a NETT center (n � 432). Overall, therewere highly statistically significant changes in allmeasures of exercise capacity, dyspnea, and qualityof life except for the SF-36 pain score. With theexception of slightly less hyperinflation (ie, a de-crease in the RV/TLC ratio of 0.6%), as expected,there were no significant changes in lung function.Improvements were significantly greater in patientswithout prior rehabilitation experience than for those
with prior rehabilitation for measures of maximumwork; 6-min walk distance; St. George total, activity,and impacts scores; UCSD Shortness of Breathscore; and SF-36 scores of physical health summary,and components of physical functioning, emotionalwell-being, and general health perceptions. Therewere no significant differences in changes for pa-tients who completed the prerandomization rehabil-itation program at satellite centers vs NETT centers.
Box plots for changes in maximum cycle workload,St. George Respiratory Questionnaire total score,and UCSD Shortness of Breath Questionnaire scorefor all patients, as well as for those with and withoutprior pulmonary rehabilitation experience, are pre-sented in Figure 1. These demonstrate greater im-
Table 2—Response to Rehabilitation: Changes from Prerehabilitation to Postrehabilitation for All Patients and byPrior Rehabilitation Experience*
*Values are given as the mean � SD. See Table 1 for abbreviations and explanations not given in the text.†p � 0.001 from the paired t test or signed rank test when nonnormal.‡p � 0.01 from the two-sample t test comparing patients with prior rehabilitation and those without prior rehabilitation. No differences wereobserved comparing rehabilitation at NETT centers only vs that at NETT plus satellite centers.
provements in patients without prior rehabilitation.Approximately half of the NETT patients demon-strated clinically important improvements for each ofthese measures based on investigator estimates ofminimal clinically important differences, as follows:cycle workload, 5 W; St. George Respiratory Ques-tionnaire total score, 4 U20; and UCSD Shortness ofBreath Questionnaire score, 5 U.21
Changes in the eight subscales of the SF-36 healthprofile are presented in Figure 2. After pulmonaryrehabilitation, seven of the eight subscales showedsignificant improvement. Only the bodily pain score,which had been nearly normal at baseline, failed toimprove.
Predictors of Improvement in PulmonaryRehabilitation
The results of the multivariate analyses of deter-minants of changes after pulmonary rehabilitationare presented in Table 3. In general, the amount ofvariability explained by the independent variableswas very small, suggesting that the changes afterpulmonary rehabilitation cannot be explained usingprerehabilitation measures. Because of significantdifferences between NETT centers with respect tochanges in maximum workload and St. George Re-spiratory Questionnaire total score, the estimates forthese dependent variables were adjusted by NETTclinic. There were no significant differences betweencenters for the UCSD Shortness of Breath Question-naire score.
Effect of Pulmonary Rehabilitation on NETTSubgroups
Prerandomization pulmonary rehabilitation had asignificant effect on NETT subgroup assignment
Figure 1. Box plots of changes from prerandomization pulmonary rehabilitation program in exercisecapacity (maximum workload), health-related quality of life (St. George Respiratory Questionnaire totalscore), and dyspnea (UCSD Shortness of Breath [SOB] Questionnaire score) for all 1,218 patients, aswell as for subgroups with and without prior pulmonary rehabilitation experience. Dashed linesrepresent the following estimated minimal clinically important differences: 5-W increase for maximumworkload; 4-U decrease for the St. George Respiratory Questionnaire total score; and 5-U decrease forthe UCSD Shortness of Breath Questionnaire score.
Figure 2. Changes in the subscales of the SF-36. PF � physicalfunctioning; RP � role limit (physical health problems); Pain � bodilypain; GH � general health perceptions; EF � energy/fatigue;SF � social functioning; RE � role limit (personal/emotional prob-lems); EW � emotional well-being (higher values indicate betterquality of life); Pre Rehab � prerehabilitation; Post Rehab �postrehabilitation.
based on maximum exercise capacity for all non-high-risk patients11,12 as well as for subgroups withand without prior rehabilitation experience (Table4). Overall, 20% of patients changed subgroup afterrehabilitation, 13.5% from the low exercise subgroupto the high exercise subgroup and 6.5% from the
high exercise subgroup to the low exercise sub-groups. The effect of rehabilitation on subgroupassignment was greater for patients without priorrehabilitation in whom 16.5% changed from the lowexercise subgroup to the high exercise subgroup and6.2% from the high exercise subgroup to the lowexercise subgroup.
Effects of Pulmonary Rehabilitation on PrimaryNETT Outcome Measures
In multivariate analyses, changes in exercise, dys-pnea, and quality of life after pulmonary rehabilita-tion were not significant predictors of differentialmortality and change in maximum cycle work (theprimary outcomes of NETT) by treatment group(data not shown).
Discussion
The NETT study provides a remarkable demon-stration of the effectiveness of pulmonary rehabilita-tion in a large cohort of patients with advancedemphysema who had been treated in a cross-sectionof programs in the United States. The study was notdesigned specifically to evaluate pulmonary rehabil-itation, and there was no comparison group withoutrehabilitation. Nevertheless, significant improve-
Table 4—Classification of Patients Into High and LowExercise NETT Subgroups Before and After PulmonaryRehabilitation for All Non-High-Risk Patients as wellas Those Patients With and Without Prior Experience
of Pulmonary Rehabilitation
Patients
Before
p Value*Low High
All non-high-risk patients (n � 1,078)After � 0.001
Low 369 70High 145 494
All non-high risk patients with priorrehabilitation (n � 672)
After 0.003Low 233 45High 78 316
All non-high risk patients with no priorrehabilitation (n � 406)
After � 0.001Low 136 25High 67 178
*From McNemar test.
Table 3—Multivariate Regression Model Estimates and 95% Confidence Limits for Change in Function or Qualityof Life Before and After Rehabilitation*
Outcome Covariate
Coefficients
p ValueEstimate† 95% CI
Change in maximum exercise capacity (R2 � 0.11)Age, yr � 0.17 � 0.27, � 0.07 0.001Gender (female vs male) � 4.09 � 5.44, � 2.74 � 0.001Prior participation in rehabilitation (no vs yes) 1.59 0.30, 2.89 0.02
Change in St. George Respiratory Questionnaire score (R2 � 0.25)Prior participation in rehabilitation (no vs yes) � 1.68 � 2.74, � 0.62 0.002IC in 0.1 L � 0.10 � 0.19, � 0.01 0.03SF-36 physical summary score � 0.16 � 0.25, � 0.08 � 0.001SF-36 mental summary score � 0.08 � 0.14, � 0.03 0.004UCSD SOB score 0.09 0.05, 0.13 � 0.001
Change in UCSD SOB score (R2 � 0.23)Prior participation in rehabilitation (no vs yes) � 2.70 � 4.10, � 1.31 � 0.001IC in 0.1 L � 0.30 � 0.42, � 0.18 � 0.001FEV1 % predicted � 0.18 � 0.27, � 0.08 � 0.001SF-36 physical summary score � 0.22 � 0.33, � 0.11 � 0.001St. George Respiratory Questionnaire score 0.16 0.09, 0.23 � 0.001
*SOB � shortness of breath. See Table 1 for other abbreviations not used in the text. Covariates included in the regression analyses weretreatment group, age, gender, center identification, prerehabilitation value for the dependent variable, plus candidate variables with p values� 0.15 in the univariate analysis, as indicated in the text. Variables identified in the final model were selected if the p values from forwardselection were � 0.05.
†Estimated increase or decrease in the change in functional outcome or quality-of-life outcome per unit increase in a continuous variable orcomparing two groups for binary variables after adjusting for the baseline value. The estimates for the change in maximum exercise capacity andSt. George Respiratory Questionnaire score were also adjusted for clinic because there were some differences by clinic.
ments in exercise capacity, dyspnea, and health-related quality of life were observed consistentlyacross many of the NETT centers (17) and satellitecenters (539). The only variable that consistentlydemonstrated an effect on rehabilitation outcomeswas whether the patient had rehabilitation experi-ence prior to enrolling in the NETT. As expected,those patients without prior rehabilitation experi-ence demonstrated the greatest gains.
These results confirm and extend those previouslypublished from single, specialized centers as well asother multicenter outcome studies9,22 and providestrong evidence that the benefits from pulmonaryrehabilitation as currently practiced are generaliz-able to community-based centers. In the overallanalyses, the magnitude of improvement in mostvariables was less than that typically observed insingle-center studies and less than the acceptedthresholds for clinically important differences. How-ever, patients in NETT were recruited regardless ofprior pulmonary rehabilitation experience, althoughall were required to complete the NETT pulmonaryrehabilitation program before randomization. Be-cause prior rehabilitation experience appears to haveblunted the response to pulmonary rehabilitation,the results in patients without prior rehabilitation(Table 2) may be a truer indication of the expectedresponse in this patient group. In these patients, theaverage changes after rehabilitation did reach thelevels generally considered to represent clinicallyimportant differences for the measures of exercisecapacity, dyspnea, and health-related quality of life.
It should also be noted that patients enrolled inthe NETT had more severe obstructive lung diseasethan that typically found in pulmonary rehabilitationprograms. The mean FEV1 in the NETT (26.9%predicted) was lower than that reported in any studyin one evidence-based review (range, 35 to 80%predicted; median, 43% predicted).1
We attempted to standardize the NETT rehabili-tation protocol by training all rehabilitation staff andcertifying satellite centers. Even among the 17NETT centers, there were some significant center-specific differences in the magnitude of change inmaximum exercise capacity and the St. George Re-spiratory Questionnaire score. There were no signif-icant center differences noted in the UCSD Short-ness of Breath Questionnaire score, indicating thatimprovements in dyspnea were quite consistent.
Although measured changes in the rehabilitationprogram were not predictors of a differential effecton the primary outcome measures in NETT bytreatment (survival or maximum exercise capacity),our experience suggests that pulmonary rehabilita-tion did play an important role in evaluating andpreparing patients for surgery and in maintaining
patients in the study. In designing the NETT proto-col, we were quite concerned about the difficulties inmaintaining subject compliance with the challengingstudy requirements. It was thought that close contactwith the pulmonary rehabilitation staff during theprerandomization and immediate postrandomizationphases would be important in ensuring that patientsfully understood the study requirements and werecommitted to returning for follow-up, regardless oftheir treatment assignment. Although there are nodata that are specific to the effect of rehabilitation,the impression of many centers was that this was acritical element in the extraordinary adherence totreatment achieved in the NETT.
Besides optimizing preoperative physical andemotional function, an important function of pulmo-nary rehabilitation was to help select appropriatepatients for surgery and to ensure that patients madea truly informed choice about treatment options.Although we cannot quantify it precisely, the expe-rience in the NETT was that many patients (perhaps10%) who came to the study eager for surgeryexperienced such positive effects from pulmonaryrehabilitation that they were subsequently unwillingto proceed to randomization and accept the surgicalrisks. Other patients, who might have initiallyseemed appropriate for surgery, were subsequentlyfound during pulmonary rehabilitation to be too ill orfragile for surgery.
In extrapolating NETT results to clinical practice,the subgroups identified on the basis of postrehabili-tation exercise capacity proved to be important.These results demonstrated that 20% of patientschanged their subgroup designation after rehabilita-tion. Although most of these changes (67%) werefrom the low exercise subgroup to the high exercisesubgroup, some patients (33%) changed from thehigh (33%) to the low exercise subgroup. Thisoccurred slightly more commonly in patients withprior rehabilitation experience (37% vs 27% of sub-group changes, respectively) who may have alreadyachieved maximum benefit from rehabilitation.However, this was also due to patients experiencingexacerbations during rehabilitation that impededtheir progress but were not severe enough to preventthem from completing the program and qualifyingfor randomization.
Despite the extensive requirements of NETT andthe out-of-pocket expenses, many patients traveledlong distances and made a considerable effort toparticipate. In designing the pulmonary rehabilita-tion program for the NETT, we were concernedabout the variability in services that might be pro-vided in so many satellite centers, but wanted tomake the protocol as available as possible to patientsthroughout the country. The fact that 65% of ran-
domized patients utilized satellite centers indicatesthe strong motivation of many patients and justifiesthe inclusion of geographically dispersed centers. Inretrospect, the relative consistency of improvementsfrom pulmonary rehabilitation observed across cen-ters in the NETT relieves these concerns.
Although these analyses focus on the prerandom-ization phase of pulmonary rehabilitation, it shouldbe remembered that the NETT rehabilitation pro-gram was designed to be a daily home-care programthat was continued throughout the study. Patientswere required to return for additional supervisedvisits after randomization and were monitored foradherence through regular telephone and in-personcontacts. Also, NETT centers had the option ofprescribing additional supervised rehabilitation ses-sions if they were deemed necessary. This is dis-tinctly different from the usual practice of pulmo-nary rehabilitation that is often restricted to onetreatment period of a few months duration andwithout allowance for continued follow-up, reassess-ment, or retreatment.
Overall, pulmonary rehabilitation in the NETTproduced significant benefits for these patients withadvanced emphysema and played an important rolein the selection of appropriate patients for possibleLVRS. The consistency of the results, both in theNETT centers and at the satellite centers, demon-strates the effectiveness of pulmonary rehabilitationin the management of patients with chronic lungdiseases.
Appendix: NETT Credit Roster
Members of the NETT Research Group
Office of the Chair of the Steering Committee, University ofPennsylvania, Philadelphia, PA: Alfred P. Fishman, MD (Chair);Betsy Ann Bozzarello; and Ameena Al-Amin.
Clinical Centers
Baylor College of Medicine, Houston, TX: Marcia Katz, MD(Principal Investigator); Carolyn Wheeler, RN, BSN (PrincipalClinic Coordinator); Elaine Baker, RRT, RPFT; Peter Barnard,PhD, RPFT; Phil Cagle, MD; James Carter, MD; Sophia Chat-ziioannou, MD; Karla Conejo-Gonzales; Kimberly Dubose, RRT;John Haddad, MD; David Hicks, RRT, RPFT; Neal Kleiman,MD; Mary Milburn-Barnes, CRTT; Chinh Nguyen, RPFT; Mi-chael Reardon, MD; Joseph Reeves-Viets, MD; Steven Sax, MD;Amir Sharafkhaneh, MD; Owen Wilson, PhD; Christine YoungPT; Rafael Espada, MD (Principal Investigator from 1996 to2002); Rose Butanda (from 1999 to 2001); Minnie Ellisor (2002);Pamela Fox, MD (from 1999 to 2001); Katherine Hale, MD(from 1998 to 2000); Everett Hood, RPFT (from 1998 to 2000);Amy Jahn (from 1998 to 2000); Satish Jhingran, MD (from 1998to 2001); Karen King, RPFT (from 1998 to 1999); Charles MillerIII, PhD (from 1996 to 1999); Imran Nizami, MD (Co-PrincipalInvestigator, from 2000 to 2001); Todd Officer (from 1998 to
2000); Jeannie Ricketts (1998 �2000); Joe Rodarte, MD (Co-Principal Investigator from 1996 to 2000); Robert Teague, MD(Co-Principal Investigator from 1999 to 2000); and KedrenWilliams (from 1998 to 1999).
Brigham and Women’s Hospital, Boston, MA: John Reilly, MD(Principal Investigator); David Sugarbaker, MD (Co-PrincipalInvestigator); Carol Fanning, RRT (Principal Clinic Coordina-tor); Simon Body, MD; Sabine Duffy, MD; Vladmir Formanek,MD; Anne Fuhlbrigge, MD; Philip Hartigan, MD; SarahHooper, EP; Andetta Hunsaker, MD; Francine Jacobson, MD;Marilyn Moy, MD; Susan Peterson, RRT; Roger Russell, MD;Diane Saunders; and Scott Swanson, MD (Co-Principal Investi-gator, from 1996 to 2001).
Cedars-Sinai Medical Center, Los Angeles, CA: Rob McKenna,MD (Principal Investigator); Zab Mohsenifar, MD (Co-PrincipalInvestigator); Carol Geaga, RN (Principal Clinic Coordinator);Manmohan Biring, MD; Susan Clark, RN, MN; Jennifer Cutler,MD; Robert Frantz, MD; Peter Julien, MD; Michael Lewis, MD;Jennifer Minkoff-Rau, MSW; Valentina Yegyan, BS, CPFT; andMilton Joyner, BA (from 1996 to 2002).
Cleveland Clinic Foundation, Cleveland, OH: Malcolm De-Camp, MD (Principal Investigator); James Stoller, MD (Co-Principal Investigator); Yvonne Meli, RN, C (Principal ClinicCoordinator); John Apostolakis, MD; Darryl Atwell, MD; JeffreyChapman, MD; Pierre DeVilliers, MD; Raed Dweik, MD; ErikKraenzler, MD; Rosemary Lann, LISW; Nancy Kurokawa, RRT,CPFT; Scott Marlow, RRT; Kevin McCarthy, RCPT; PricillaMcCreight, RRT, CPFT; Atul Mehta, MD; Moulay Meziane,MD; Omar Minai, MD; Mindi Steiger, RRT; Kenneth White,RPFT; Janet Maurer, MD (Principal Investigator, from 1996 to2001); Terri Durr, RN (from 2000 to 2001); Charles Hearn, DO(from 1998 to 2001); Susan Lubell, PA-C (from 1999 to 2000);Peter O’Donovan, MD (from 1998 to 2003); and Robert Schilz,DO (from 1998 to 2002).
Columbia University, New York, NY, in consortium with LongIsland Jewish Medical Center, New Hyde Park, NY: MarkGinsburg, MD (Principal Investigator); Byron Thomashow, MD(Co-Principal Investigator); Patricia Jellen, MSN, RN (PrincipalClinic Coordinator); John Austin, MD; Matthew Bartels, MD;Yahya Berkmen, MD; Patricia Berkoski, MS, RRT (Site coordi-nator, LIJ); Frances Brogan, MSN, RN; Amy Chong, BS, CRT;Glenda DeMercado, BSN; Angela DiMango, MD; Sandy Do,MS, PT; Bessie Kachulis, MD; Arfa Khan, MD; Berend Mets,MD; Mitchell O’ Shea, BS, RT, CPFT; Gregory Pearson, MD;Leonard Rossoff, MD; Steven Scharf, MD, PhD (Co-PrincipalInvestigator, from 1998 to 2002); Maria Shiau, MD; Paul Simo-nelli, MD; Kim Stavrolakes, MS, PT; Donna Tsang, BS; DeniseVilotijevic, MS, PT; Chun Yip, MD; Mike Mantinaos, MD (from1998 to 2001); Kerri McKeon, BS, RRT, RN (from 1998 to 1999);and Jacqueline Pfeffer, MPH, PT (from 1997 to 2002).
Duke University Medical Center, Durham, NC: Neil MacIn-tyre, MD (Principal Investigator); R. Duane Davis, MD (Co-Principal Investigator); John Howe, RN (Principal Clinic Coor-dinator); R. Edward Coleman, MD; Rebecca Crouch, RPT; DoraGreene; Katherine Grichnik, MD; David Harpole, Jr., MD; AbbyKrichman, RRT; Brian Lawlor, RRT; Holman McAdams, MD;John Plankeel, MD; Susan Rinaldo-Gallo, MED; Sheila Shearer,RRT; Jeanne Smith, ACSW; Mark Stafford-Smith, MD; VictorTapson, MD; Mark Steele, MD (from 1998 to 1999); and JenniferNorten, MD (from 1998 to 1999).
Mayo Foundation, Rochester, MN: James Utz, MD (PrincipalInvestigator); Claude Deschamps, MD (Co-Principal Investiga-tor); Kathy Mieras, CCRP (Principal Clinic Coordinator); MartinAbel, MD; Mark Allen, MD; Deb Andrist, RN; Gregory Augh-enbaugh, MD; Sharon Bendel, RN; Eric Edell, MD; MarleneEdgar; Bonnie Edwards; Beth Elliot, MD; James Garrett, RRT;Delmar Gillespie, MD; Judd Gurney, MD; Boleyn Hammel;
Karen Hanson, RRT; Lori Hanson, RRT; Gordon Harms, MD;June Hart; Thomas Hartman, MD; Robert Hyatt, MD; EricJensen, MD; Nicole Jenson, RRT; Sanjay Kalra, MD; PhilipKarsell, MD; Jennifer Lamb; David Midthun, MD; Carl Mot-tram, RRT; Stephen Swensen, MD; Anne-Marie Sykes, MD;Karen Taylor; Norman Torres, MD; Rolf Hubmayr, MD (from1998 to 2000); Daniel Miller, MD (from 1999 to 2002); SaraBartling, RN (from 1998 to 2000); and Kris Bradt (from 1998 to2002).
National Jewish Medical and Research Center, Denver, CO:Barry Make, MD (Principal Investigator); Marvin Pomerantz,MD (Co-Principal Investigator); Mary Gilmartin, RN, RRT(Principal Clinic Coordinator); Joyce Canterbury; Martin Carlos;Phyllis Dibbern, PT; Enrique Fernandez, MD; Lisa Geyman,MSPT; Connie Hudson; David Lynch, MD; John Newell, MD;Robert Quaife, MD; Jennifer Propst, RN; Cynthia Raymond,MS; Jane Whalen-Price, PT; Kathy Winner, OTR; MartinZamora, MD; and Reuben Cherniack, MD (Principal Investiga-tor, from 1997 to 2000).
Ohio State University, Columbus, OH: Philip Diaz, MD(Principal Investigator); Patrick Ross, MD (Co-Principal Investi-gator); Tina Bees (Principal Clinic Coordinator); Jan Drake;Charles Emery, PhD; Mark Gerhardt, MD, PhD; Mark King,MD; David Rittinger; and Mahasti Rittinger.
Saint Louis University, Saint Louis, MO: Keith Naunheim,MD (Principal Investigator); Robert Gerber, MD (Co-PrincipalInvestigator); Joan Osterloh, RN, MSN (Principal Clinic Coordi-nator); Susan Borosh; Willard Chamberlain, DO; Sally Frese;Alan Hibbit; Mary Ellen Kleinhenz, MD; Gregg Ruppel; CaryStolar, MD; Janice Willey; Francisco Alvarez, MD (Co-PrincipalInvestigator, from 1999 to 2002); and Cesar Keller, MD (Co-Principal Investigator, from 1996 to 2000).
Temple University, Philadelphia, PA: Gerard Criner, MD(Principal Investigator); Satoshi Furukawa, MD (Co-PrincipalInvestigator); Anne Marie Kuzma, RN, MSN (Principal ClinicCoordinator); Roger Barnette, MD; Neil Brister, MD; KevinCarney, RN, CCTC; Wissam Chatila, MD; Francis Cordova,MD; Gilbert D’Alonzo, DO; Michael Keresztury, MD; KarenKirsch; Chul Kwak, MD; Kathy Lautensack, RN, BSN; MadelinaLorenzon, CPFT; Ubaldo Martin, MD; Peter Rising, MS; ScottSchartel, MD; John Travaline, MD; Gwendolyn Vance, RN,CCTC; Phillip Boiselle, MD (from 1997 to 2000); and Gerald O’Brien, MD (from 1997 to 2000).
University of California, San Diego, San Diego, CA: AndrewRies, MD, MPH (Principal Investigator); Robert Kaplan, PhD(Co-Principal Investigator); Catherine Ramirez, BS, RCP (Prin-cipal Clinic Coordinator); David Frankville, MD; Paul Friedman,MD; James Harrell, MD; Jeffery Johnson; David Kapelanski,MD; David Kupferberg, MD, MPH; Catherine Larsen, MPH;Trina Limberg, RRT; Michael Magliocca, RN, CNP; Frank J.Papatheofanis, MD, PhD; Dawn Sassi-Dambron, RN; and Mel-issa Weeks.
University of Maryland at Baltimore, Baltimore, MD, inconsortium with Johns Hopkins Hospital, Baltimore, MD: MarkKrasna, MD (Principal Investigator); Henry Fessler, MD (Co-Principal Investigator); Iris Moskowitz (Principal Clinic Coordi-nator); Timothy Gilbert, MD; Jonathan Orens, MD; StevenScharf, MD, PhD; David Shade; Stanley Siegelman, MD; Ken-neth Silver, MD; Clarence Weir; and Charles White, MD.
University of Michigan, Ann Arbor, MI: Fernando Martinez,MD (Principal Investigator); Mark Iannettoni, MD (Co-PrincipalInvestigator); Catherine Meldrum, BSN, RN, CCRN (PrincipalClinic Coordinator); William Bria, MD; Kelly Campbell; PaulChristensen, MD; Kevin Flaherty, MD; Steven Gay, MD;Paramjit Gill, RN; Paul Kazanjian, MD; Ella Kazerooni, MD;Vivian Knieper; Tammy Ojo, MD; Lewis Poole; Leslie Quint,
MD; Paul Rysso; Thomas Sisson, MD; Mercedes True; BrianWoodcock, MD; and Lori Zaremba, RN.
University of Pennsylvania, Philadelphia, PA: Larry Kaiser,MD (Principal Investigator); John Hansen-Flaschen, MD (Co-Principal Investigator); Mary Louise Dempsey, BSN, RN (Prin-cipal Clinic Coordinator); Abass Alavi, MD; Theresa Alcorn,Selim Arcasoy, MD; Judith Aronchick, MD; Stanley Aukberg,MD; Bryan Benedict, RRT; Susan Craemer, BS, RRT, CPFT;Ron Daniele, MD; Jeffrey Edelman, MD; Warren Gefter, MD;Laura Kotler-Klein, MSS; Robert Kotloff, MD; David Lipson,MD; Wallace Miller, Jr., MD; Richard O’ Connell, RPFT; StaciOpelman, MSW; Harold Palevsky, MD; William Russell, RPFT;Heather Sheaffer, MSW; Rodney Simcox, BSRT, RRT; SusanneSnedeker, RRT, CPFT; Jennifer Stone-Wynne, MSW; GregoryTino, MD; Peter Wahl; James Walter, RPFT; Patricia Ward;David Zisman, MD; James Mendez, MSN, CRNP (from 1997 to2001); and Angela Wurster, MSN, CRNP (from 1997 to 1999).
University of Pittsburgh, Pittsburgh, PA: Frank Sciurba, MD(Principal Investigator); James Luketich, MD (Co-Principal In-vestigator); Colleen Witt, MS (Principal Clinic Coordinator);Gerald Ayres; Michael Donahoe, MD; Carl Fuhrman, MD;Robert Hoffman, MD; Joan Lacomis, MD; Joan Sexton; WilliamSlivka; Diane Strollo, MD; Erin Sullivan, MD; Tomeka Simon;Catherine Wrona, RN, BSN; Gerene Bauldoff, RN, MSN (from1997 to 2000); Manuel Brown, MD (from 1997 to 2002);Elisabeth George, RN, MSN (Principal Clinic Coordinator from1997 to 2001); Robert Keenan, MD (Co-Principal Investigatorfrom 1997 to 2000); Theodore Kopp, MS (from 1997 to 1999);and Laurie Silfies (from 1997 to 2001).
University of Washington, Seattle, WA: Joshua Benditt, MD(Principal Investigator), Douglas Wood, MD (Co-Principal In-vestigator); Margaret Snyder, MN (Principal Clinic Coordinator);Kymberley Anable; Nancy Battaglia; Louie Boitano; AndrewBowdle, MD; Leighton Chan, MD; Cindy Chwalik; Bruce Cul-ver, MD; Thurman Gillespy, MD; David Godwin, MD; JeanneHoffman; Andra Ibrahim, MD; Diane Lockhart; Stephen Mar-glin, MD; Kenneth Martay, MD; Patricia McDowell; DonaldOxorn, MD; Liz Roessler; Michelle Toshima; and Susan Golden(from 1998 to 2000).
Other Participants
Agency for Healthcare Research and Quality, Rockville, MD:Lynn Bosco, MD, MPH; Yen-Pin Chiang, PhD; Carolyn Clancy,MD; and Harry Handelsman, DO.
Centers for Medicare and Medicaid Services, Baltimore, MD:Steven M Berkowitz, PhD; Tanisha Carino, PhD; Joe Chin, MD;JoAnna Baldwin; Karen McVearry; Anthony Norris; Sarah Shirey;Claudette Sikora; and Steven Sheingold, PhD (from 1997 to2004).
Coordinating Center, The Johns Hopkins University, Balti-more, MD: Steven Piantadosi, MD, PhD (Principal Investigator);James Tonascia, PhD (Co-Principal Investigator); Patricia Belt;Amanda Blackford, ScM; Karen Collins; Betty Collison; RyanColvin, MPH; John Dodge; Michele Donithan, MHS; VeraEdmonds; Gregory L. Foster, MA; Julie Fuller; Judith Harle;Rosetta Jackson; Shing Lee, ScM; Charlene Levine; Hope Liv-ingston; Jill Meinert; Jennifer Meyers; Deborah Nowakowski;Kapreena Owens; Shangqian Qi, MD; Michael Smith; BrettSimon, MD; Paul Smith; Alice Sternberg, ScM; Mark Van Natta,MHS; Laura Wilson, ScM; and Robert Wise, MD.
Cost Effectiveness Subcommittee: Robert M. Kaplan, PhD(Chair); J. Sanford Schwartz, MD (Co-Chair); Yen-Pin Chiang,PhD; Marianne C. Fahs, PhD; A. Mark Fendrick, MD; Alan J.Moskowitz, MD; Dev Pathak, PhD; Scott Ramsey, MD, PhD;Steven Sheingold, PhD; A. Laurie Shroyer, PhD; Judith Wagner,PhD; and Roger Yusen, MD.
Cost Effectiveness Data Center, Fred Hutchinson CancerResearch Center, Seattle, WA: Scott Ramsey, MD, PhD (Princi-pal Investigator); Ruth Etzioni, PhD; Sean Sullivan, PhD; Doug-las Wood, MD; Thomas Schroeder, MA; Karma Kreizenbeck;Kristin Berry, MS; and Nadia Howlader, MS.
CT Scan Image Storage and Analysis Center, University ofIowa, Iowa City, IA: Eric Hoffman, PhD (Principal Investigator);Janice Cook-Granroth, BS; Angela Delsing, RT; Junfeng Guo,PhD; Geoffrey McLennan, MD; Brian Mullan, MD; Chris Piker,BS; Joseph Reinhardt, PhD; Blake Robinswood; Jered Sieren,RTR; and William Stanford, MD.
Data and Safety Monitoring Board: John A. Waldhausen, MD(Chair); Gordon Bernard, MD; David DeMets, PhD; MarkFerguson, MD; Eddie Hoover, MD; Robert Levine, MD;Donald Mahler, MD; A. John McSweeny, PhD; Jeanine Wiener-Kronish, MD; O. Dale Williams, PhD; and Magdy Younes, MD.
Marketing Center, Temple University, Philadelphia, PA: Ger-ard Criner, MD (Principal Investigator); and Charles Soltoff,MBA.
Project Office, National Heart, Lung, and Blood Institute,Bethesda, MD: Gail Weinmann, MD (Project Officer); JoanneDeshler (Contracting Officer); Dean Follmann, PhD; JamesKiley, PhD; and Margaret Wu, PhD (from 1996 to 2001).
Other Acknowledgments
Arthur Gelb, MD, Lakewood Regional Medical Center, Lake-wood, CA.
References1 American College of Chest Physicians and American Associ-
ation of Cardiovascular and Pulmonary Rehabilitation.Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based guidelines; ACCP/AACVPR Pulmonary RehabilitationGuidelines Panel. Chest 1997; 112:1363–1396
2 American College of Chest Physicians and American Associ-ation of Cardiovascular and Pulmonary Rehabilitation.ACCP-AACVPR Pulmonary Rehabilitation Guidelines Panel:pulmonary rehabilitation; joint ACCP/AACVPR evidencebased guidelines. J Cardiopulm Rehabil 1997; 17:371–405
3 American Thoracic Society. Standards for the diagnosis andcare of patients with chronic obstructive pulmonary disease(COPD) and asthma. Am Rev Respir Dis 1995; 152:S78–S121
4 Lacasse Y, Wong E, Guyatt GH, et al. Meta-analysis ofrespiratory rehabilitation in chronic obstructive pulmonarydisease. Lancet 1996; 348:1115–1119
5 Cambach W, Wagenaar RC, Koelman TW, et al. The long-term effects of pulmonary rehabilitation in patients withasthma and chronic obstructive disease: a research synthesis.
Arch Phys Med Rehabil 1999; 80:103–1116 Casaburi R, Petty TL. Principles and practice of pulmonary
tion: guidelines to success. 3rd ed. Philadelphia, PA: Lippin-cott Williams & Wilkins, 2000
8 American Association of Cardiovascular and Pulmonary Re-habilitation. Guidelines for pulmonary rehabilitation pro-grams. 3rd ed. Champaign, IL: Human Kinetics, 2004
9 California Pulmonary Rehabilitation Collaborative Group.Effects of pulmonary rehabilitation on dyspnea, quality of lifeand health care costs in California. J Cardiopulm Rehabil2004; 24:52–62
10 National Emphysema Treatment Trial Research Group. Ra-tionale and design of the National Emphysema TreatmentTrial (NETT): a prospective randomized trial of lung volumereduction surgery. Chest 1999; 116:1750–1761
11 National Emphysema Treatment Trial Research Group. Arandomized trial comparing lung-volume-reduction surgerywith medical therapy for severe emphysema. N Engl J Med2003; 348:2059–2073
12 National Emphysema Treatment Trial Research Group. Pa-tients at high risk of death after lung-volume-reductionsurgery. N Engl J Med 2001; 345:1075–1083
13 National Emphysema Treatment Trial Research Group. Costeffectiveness of lung-volume-reduction surgery for patientswith severe emphysema. N Engl J Med 2003; 348:2092–2102
14 Beck AT, Ward CH, Mendelson M, et al. An inventory formeasuring depression. Arch Gen Psychiatry 1961; 4:561–571
17 Reitan R. Validity of the trail making test as an indicator oforganic brain damage. Percept Mot Skills 1958; 8:271–276
18 Jones PW, Quirk FH, Baveystock CM, et al. A self-completemeasure of health status for chronic airflow limitation. AmRev Respir Dis 1992; 145:1321–1327
19 Eakin EG, Resnikoff PM, Prewitt LM, et al. Validation of anew dyspnea measure: the UCSD Shortness of Breath Ques-tionnaire. Chest 1998; 113:619–624
20 Jones PW. Interpreting thresholds for a clinically significantchange in health status in asthma and COPD. Eur Respir J2002; 19:398–404
21 Ries AL. Minimally clinically important difference for theUCSD Shortness of Breath Questionnaire, Borg Scale, andVisual Analog Scale. COPD: J Chronic Obstruct Pulm Dis2005; 2:105–110
22 Haggerty MC, Stockdale-Woolley R, ZuWallack R. Func-tional status in pulmonary rehabilitation participants. J Car-diopulm Rehabil 1999; 19:35–42
DOI 10.1378/chest.128.6.3799 2005;128; 3799-3809Chest
Bartels, Rebecca Crouch and Alfred P. FishmanAndrew L. Ries, Barry J. Make, Shing M. Lee, Mark J. Krasna, Matthew
*Treatment TrialThe Effects of Pulmonary Rehabilitation in the National Emphysema
August 3, 2009This information is current as of
& ServicesUpdated Information
http://www.chestjournal.org/content/128/6/3799.full.htmlhigh-resolution figures, can be found at:Updated Information and services, including
References
html#ref-list-1http://www.chestjournal.org/content/128/6/3799.full.accessed free at:This article cites 17 articles, 8 of which can be
Citations
html#related-urlshttp://www.chestjournal.org/content/128/6/3799.full.articles:This article has been cited by 5 HighWire-hosted
Open AccessoptionFreely available online through CHEST open access
Permissions & Licensing
http://www.chestjournal.org/site/misc/reprints.xhtml(figures, tables) or in its entirety can be found online at: Information about reproducing this article in parts
