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* A complete list of NETT investigators is located in the Appendix.
Correspondence to: Steven Piantadosi, MD, PhD, The National Emphysema Treatment Trial Coordinating Center, Johns Hopkins Center for Clinical Trials, Room 5010, Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe St, Baltimore, MD 21205
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Abstract |
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 TOP Abstract IntroductionTerminologyPresent State of Treatment...Surgery for EmphysemaExisting Data on LVRSRationale for the TrialOutcome MeasuresStudy DesignTreatments in the NETTStatistical ConsiderationsPatient Rights and...ConclusionAppendix: NETT InvestigatorsReferences |
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Key Words: emphysema • lung function • lung volume reduction surgery • maximum exercise capacity • median sternotomy • medical vs surgical treatment • pulmonary rehabilitation • randomized clinical trial • video-assisted thoracoscopic surgery
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Introduction |
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TOPAbstractIntroductionTerminologyPresent State of Treatment...Surgery for EmphysemaExisting Data on LVRSRationale for the TrialOutcome MeasuresStudy DesignTreatments in the NETTStatistical ConsiderationsPatient Rights and...ConclusionAppendix: NETT InvestigatorsReferences |
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Terminology |
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TOPAbstractIntroductionTerminologyPresent State of Treatment...Surgery for EmphysemaExisting Data on LVRSRationale for the TrialOutcome MeasuresStudy DesignTreatments in the NETTStatistical ConsiderationsPatient Rights and...ConclusionAppendix: NETT InvestigatorsReferences |
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1-antitrypsin deficiency.
It is a chronic progressive disorder that ultimately leads to
disability and early death. Emphysema is estimated to be present in 2
million adults in the United States, and, along with other forms of
COPD, accounts for > 90,000 deaths annually.2 |
Present State of Treatment for Emphysema |
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TOPAbstractIntroductionTerminologyPresent State of Treatment...Surgery for EmphysemaExisting Data on LVRSRationale for the TrialOutcome MeasuresStudy DesignTreatments in the NETTStatistical ConsiderationsPatient Rights and...ConclusionAppendix: NETT InvestigatorsReferences |
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Long-term domiciliary oxygen therapy in hypoxemic patients is the only
treatment for COPD that has been documented to decrease mortality
rates.14
15
Adjunctive forms of therapy, such as the use
of mucolytics to control respiratory secretions or narcotics to reduce
the sensation of dyspnea, have been used in selected COPD
patients.16
In patients with
1-protease inhibitor deficiency, protective
serum levels of the enzyme may be restored by regular infusions of
exogenous 1-protease inhibitor,17
but it is unclear whether restoring serum levels protects against
progression of the disease or prolongs survival.11
In
patients with far-advanced COPD, single or double lung transplantation
has been used as a last resort, but this option is limited by the small
number of donor organs.
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Surgery for Emphysema |
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TOPAbstractIntroductionTerminologyPresent State of Treatment...Surgery for EmphysemaExisting Data on LVRSRationale for the TrialOutcome MeasuresStudy DesignTreatments in the NETTStatistical ConsiderationsPatient Rights and...ConclusionAppendix: NETT InvestigatorsReferences |
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In 1957, Brantigan and Mueller19 reported the surgical excision of lung tissue to reduce the volume of the hyperinflated lung parenchyma, so-called "lung volume reduction surgery" (LVRS). Although 75% of patients reported clinical improvement, the lack of objective documentation for benefit from the procedure and an operative mortality of 18% prevented widespread acceptance of the procedure.
In more recent years, the concept of reducing lung volume surgically in patients with emphysema has been reexplored. In 1991, Wakabayashi et al20 reported using a carbon dioxide laser to shrink bullous areas of the lung using a thoracoscopic approach. In 1995, Cooper et al21 reported a modification of the volume reduction operation of Brantigan and Mueller,19 in which lung tissue was resected from both lungs via a median sternotomy (MS). In the initial 20 patients reported, there was no operative mortality, and the operation produced an 82% mean increase in the FEV1 and significant improvement in the distance walked in 6 min. Moreover, many patients were able to discontinue the use of supplemental oxygen. Subsequent randomized prospective studies suggested that the results using stapled resection were superior to those obtained by laser ablation22 and that bilateral resection was superior to unilateral resection.23
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Existing Data on LVRS |
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The favorable results reported in the series reported earlier contrasted with data collected from 722 Medicare claims that used the LVRS billing code between October 1995 and January 1996.30 Mortality rates 3 and 12 months postsurgery were 14.4% and 23%, respectively. For these patients, acute-care hospitalizations and use of long-term care and rehabilitation services were greater postsurgery than presurgery (304 stays for 160 patients postsurgery vs 197 stays for 123 patients presurgery; the inpatient stay associated with the LVRS was excluded from these analyses). The average number of days hospitalized was greater postsurgery than presurgery.
During the development of the NETT protocol, the historical experience with LVRS at the original 18 clinical centers was reviewed by the NETT Coordinating Center at the request of the NETT Steering Committee. The centers collectively reported 1,741 patients who had undergone LVRS by bilateral, unilateral, laser, and excision procedures. The number of patients per center undergoing LVRS ranged between 13 and 371. Data were requested on baseline prognostic variables (eg, age, sex, and pulmonary function tests), pulmonary function tests performed 6 months postoperatively, the 6-min walk test, vital status, and duration of survival. Investigators also were asked to assess each patient for whether they had benefitted from the LVRS; each investigator could use their discretion regarding the criteria for the assessment of benefit or lack of benefit. Analyses were conducted on all 1,741 patients regardless of the type of procedure used for LVRS.
The analyses showed that considerable historical data were missing, making it difficult to draw statistical inferences. For example, only 25% of the 1,741 patients had sufficient baseline and follow-up data on prognostic variables for meaningful analyses. Inferences from the historical data were compromised not only by the missing values but also by the potential for strong biases in follow-up and functional assessment. In general, investigators seemed inclined to attribute benefit to the procedure, as seen in the requested subjective assessment of benefit or no benefit. Logistic regression techniques were used on one half of the historical data set to identify baseline characteristics that would be predictive of benefit. The other half of the data set was used to determine the sensitivity and specificity of the characteristics identified as predictive of benefit. The best sensitivity and specificity for prediction of benefit were approximately 62% and 64%, respectively. In summary, the historical data did not provide convincing evidence for efficacy for or reliable characterization of a subset of patients likely to benefit from LVRS.
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Rationale for the Trial |
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Investigators at a number of medical centers across the United States tried to reproduce the data given in the initial reports of success with LVRS. At several of these sites, mortality rates were inordinately high, raising questions about the risk/benefit ratio of medical therapy vs medical therapy plus surgical intervention. Among the questions raised were the following: How long would the benefit from surgery last? What is the optimal technique for performing the procedure? What are the clinical outcomes beyond the first few months after surgery? Can a subset of patients who would benefit from the procedure be defined?
Thus, key questions remain about whether the benefits of LVRS outweigh the associated risks and costs, and about issues of efficacy, safety, and patient selection. These questions are particularly pertinent for this group of individuals, who suffer from advanced emphysematous lung disease and who are willing to try any new form of treatment that has the potential for relieving their considerable discomfort in breathing.
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Outcome Measures |
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The other primary measure of outcome, the maximum exercise capacity, was chosen as a measure of integrated cardiopulmonary and physical performance. It is determined by maximal, incremental, symptom-limited exercise using a cycle ergometer. This test affords several advantages over the 6-min walk test: it is easier to standardize, it is more reproducible, it is not difficult to administer, and it entails less of a learning effect. Exercise capacity was favored over pulmonary function tests as a primary measure of outcome because studies to date have not documented a consistent relationship between improvement in functional status and changes in pulmonary function, particularly in patients treated medically.
Secondary Measures
The following secondary measures will be in used in the assessment
of outcomes.
Quality of Life and Related Disease-Specific Symptoms: These are possibly the most important outcome measures to the patients participating in the trial, and will be measured both by general and disease-specific instruments. General quality of life will be assessed by the Medical Outcomes Study Short Form 36-item questionnaire (SF-36)31 and the utility-weighted Quality of Well-Being Scale (QWB).32 The SF-36 is widely used; its inclusion in the NETT battery will allow the comparison of results from NETT with results from other studies. The QWB is widely used to provide an estimate of quality-adjusted life years, an important measure for the cost-effectiveness analysis. Disease-specific quality of life will be assessed using the St. George’s Respiratory Questionnaire (SGRQ),33 an instrument that has been developed and validated in patients with COPD. The University of California, San Diego Shortness of Breath Questionnaire (SOBQ),34 and the modified Borg scale for perceived dyspnea35 36 will be used to assess dyspnea, the most important symptom of chronic lung disease. The SOBQ is sensitive to small changes in perceived breathlessness and provides information about breathlessness during the daily activities of patients that can be helpful in their clinical evaluation and in their management in rehabilitation. The modified Borg scale is used at the start and close of the 6-min walk testing and the maximum exercise testing to obtain ratings of perceived dyspnea and muscle fatigue before and after exercise. The SF-36, QWB, SGRQ, and SOBQ are self-administered scales that can be completed within 60 min.
Cost-effectiveness Analysis: This analysis will be performed using incremental quality-adjusted life years as the denominator and incremental costs as the numerator. Costs will include resources consumed during the course of care; values or prices will be assigned to each resource. Costs of therapy include medical and surgical care, nonmedical care related to the treatment, the time of family or friends (valued to dollars) for caring for the patient, and the value of the patient’s time obtaining treatment. The analysis will be completed both from this general societal perspective and from the Medicare perspective. The latter includes only the costs that Medicare covers. Details about the cost-effectiveness analysis will be published elsewhere.
Pulmonary Function and Gas Exchange: These will be assessed in all patients at the time of the initial evaluation and at all follow-up visits. Tests will include spirometry, plethysmographic determination of the functional residual capacity, the single-breath diffusing capacity, arterial blood gas levels at rest, and the maximal inspiratory and expiratory mouth pressures. Selected clinics will assess pulmonary mechanics in greater detail, including determinations of lung elastic recoil pressures, flow-volume relationships, pulmonary resistance, respiratory muscle function, and arterial blood gas levels during maximum exercise.
Radiologic Studies: These studies will include standard chest radiographs, volumetric and high-resolution CT scans, and nuclear perfusion scans. Chest radiographs and CT scans will be performed at the time of initial evaluation and at two follow-up visits; perfusion scans will be performed at the initial evaluation only. CT scans will be used to verify the presence of emphysema and to assess the distribution and severity of the disease.
Oxygen Requirement: The requirement of patients for supplemental oxygen will be assessed on entry into the study and in follow-up. This will be done by adjusting the oxygen concentration of inspired air to maintain the oxygen saturation of arterial blood at > 90% while the patient walks on a treadmill, on a level grade, at one mile per hour.
6-Min Walk Distance: This exercise parameter is included largely because of its widespread use by investigators who have previously reported on the results of LVRS. However, it has been designated as a secondary, rather than a primary, measure of outcome because the test is difficult to standardize.37 The test will be performed initially and during follow-up.
Cardiovascular Measures: All patients will undergo echocardiographic studies at the time of initial assessment. All patients with evidence of abnormally high pulmonary arterial pressures will undergo right heart catheterization as part of their evaluation for inclusion in the trial. Patients with pulmonary hypertension are ineligible, because of the possibility of increased surgical risk. All patients will undergo at least one follow-up echocardiographic study. At selected clinics, patients will undergo initial and follow-up right heart catheterization.
Attention and Psychomotor Functioning: The Trail Making Test38 39 will be used at baseline and at annual follow-up visits to evaluate changes in cognitive ability or performance over time. The test is included because it is informative, simple to administer, and sensitive to hypoxia.
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Study Design |
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The trial has three components:
Patient Participation
The recruitment goal for the trial is 2,500 patients; 6% of these
are expected to be of minority background, and 30% are expected to be
women. The study duration is set at 4.5 years with a 6-month close-out
period.
Patients with moderate to severe emphysema who have been nonsmokers for 6 months prior to randomization and are judged to be free of other diseases, disabilities, or circumstances likely to interfere with therapy, data collection, or both for the duration of the trial, will be offered the opportunity to enroll in the NETT.
At all clinical centers, participants, after enrollment and pulmonary rehabilitation, will be randomized to a program of medical therapy or to a program of medical therapy plus LVRS in a 1:1 ratio. At those clinical centers that offer LVRS by both MS and video-assisted thoracoscopic surgery (VATS), those patients randomized to the surgical arm will participate in a second randomization between the two surgical approaches, also in a 1:1 ratio.
Screening Process
Patients may either self-refer for evaluation at a NETT clinical
center or be referred by their physician. Patients, their physician, or
both will be asked to provide a brief history, chest radiograph, ECG
report, and the results of spirometry. These data will be reviewed at
the clinical center. Those patients without identifiable
contraindication will be invited to the clinical center for evaluation
and testing. All patients who initiate screening at a NETT clinic are
included in the NETT registry. Patients who are found to be ineligible
for randomization remain in the registry and will be followed for vital
status.
Patients invited for further evaluation will undertake a process designed to establish eligibility to be enrolled in the NETT and provide the baseline assessments that will serve as reference data for the duration of the trial. The evaluation process is outlined in Tables 1 , 2.
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Inclusion Criteria
The inclusion criteria were designed to enroll patients with
severe obstructive lung disease primarily due to emphysema. The
criteria were formulated to include patients with a diverse
distribution of emphysema to examine the effect of the anatomic
distribution of disease on the response to therapy. The inclusion
criteria include the following: (1) radiographic evidence of bilateral
emphysema; (2) studies demonstrating severe airflow obstruction and
hyperinflation; and (3) participation in pulmonary rehabilitation with
the attainment of preset performance goals (Table 3
).
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Treatments in the NETT |
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Smoking Cessation: Although eligibility for participation in NETT requires smoking cessation for at least 6 months before randomization and biochemical validation at the time of screening, it is anticipated that some participants may resume smoking during NETT. Relapses will be treated in line with the Agency for Health Care Policy and Research guidelines, including counseling, referral to group programs, and nicotine replacement therapy.
Bronchodilators: In general, treatment will include both an anticholinergic bronchodilator and a ß2-agonist. The preferred route of administration is by metered-dose inhaler.
Oxygen Therapy:
Oxygen will be administered chronically to maintain
the level of arterial oxygen saturation at 
90% during
activities of daily living.
Immunization: Influenza immunization and pneumococcal vaccination are to be used in accord with Centers for Disease Control and Prevention guidelines.
Additional Measures: Additional measures will be tailored to individual needs. These may include bronchodilators such as theophylline, administered orally, corticosteroids, administered by inhalation or orally, and antibiotics for the treatment of respiratory infections.
Pulmonary Rehabilitation: The rehabilitation program in NETT is designed to optimize the ability of the patient to perform the activities of daily living and to understand and manage the chronic disease. For participants undergoing medical therapy alone, the goal of the NETT rehabilitation program is to optimize exercise capacity. For participants undergoing medical therapy plus LVRS, the goals are to achieve as much physical fitness as possible before surgery to effect early postoperative mobilization and to provide a baseline of optimized preoperative exercise capacity for comparison with the postoperative exercise capacity.
All participants will engage in pulmonary rehabilitation, which will be conducted in three phases: prerandomization (16 to 20 sessions over 6 to 10 weeks); postrandomization (10 sessions over 8 to 9 weeks); and long-term maintenance (duration of the trial). The rehabilitation programs will be supervised by a NETT clinical center; portions of the program may be carried out at a NETT-certified rehabilitation facility closer to the participant’s home. The long-term maintenance program will be conducted at home or at a fitness center with continued monitoring performed by a NETT clinical center.
Components of the pulmonary rehabilitation program include the following:
Surgical Treatment
Based on the consensus that the excision of lung tissue using LVRS
is more effective than laser ablation or lung plication in relieving
symptoms and improving pulmonary function, and to ensure consistency
among participating centers, only stapled LVRS with excision will be
used in the trial. In addition, all patients treated surgically will
undergo bilateral reduction surgery because of the evidence that the
bilateral procedure affords greater and more consistent benefits than
does the unilateral procedure.
The surgical approach will not be uniform at all the centers. MS will be performed at 8 of the 17 centers, bilateral VATS will be performed at 3 centers, and 6 centers will randomize patients to either MS or VATS. Patients will be scheduled for surgery within 2 weeks of randomization. If exacerbation of the patient’s underlying disease or other illness causes delay beyond this time limit, surgery will be postponed until after the acute illness has subsided. Further pulmonary rehabilitation and additional testing may be required to ensure that candidates continue to satisfy inclusion criteria.
The surgical procedure is directed at excising functionally useless lung tissue. The areas to be resected are identified by preoperative CT scans and perfusion scans. Based on published experience, most patients can be expected to have heterogeneous disease, which is most severe in the upper lobes; in relatively few patients, emphysema will predominate in the lower lobes. The surgical procedure entails removal of approximately 25 to 30% of the total lung tissue from each side. Surgeons are permitted to reinforce the staple lines using buttress material to minimize the incidence and severity of air leaks. Removed tissue will be weighed, and portions will be stored for possible use in future studies. For each patient, details of the operation will be recorded that pay special attention to the extent of adhesions, intraoperative difficulties, and problems with intraoperative hemodynamics.
Intraoperative management of anesthesia has been standardized. Preoperatively, in MS patients, thoracic epidural catheters will be placed for intra- and postoperative pain control. It is expected that extubation will be performed within 2 h, either in the operating room or the recovery area. Patients will be admitted either to the ICU or to another designated unit in line with the standard of care for patients undergoing major thoracic surgery at the respective institution. Starting on the first postoperative day, patients will receive vigorous chest respiratory therapy and physical therapy to enhance mobilization.
Based on previous experience, the most significant postoperative
complication is expected to be air leaks that last > 7 days. This
problem is likely to affect 
40% of surgical patients regardless of
the technique used for LVRS. Other significant complications to be
anticipated include respiratory failure, especially if reintubation is
necessary, cardiac dysrhythmia, and GI complications.
Individual centers may choose to discharge patients with air leaks controlled by the use of Heimlich valves on the chest tube(s). The date of discharge from the surgical facility, as well as the disposition of the patient (home or another in-patient facility, for example), will be recorded.
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Statistical Considerations |
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The primary treatment comparisons will be between medical therapy and LVRS of either type (MS or VATS). However, the structure and size of the trial will also permit important subset analyses to be conducted, as well as comparisons of morbidity, mortality, and other outcomes within the surgery group. These differences will be assessed with lower power than the primary comparison, but they should permit clinically important differences to be detected. An important objective of the trial is to gather information to characterize any subset of patients who might receive disproportionate benefit (or risk) from the surgical procedure.
Power and Sample Size
This trial is designed primarily to determine the difference in
survival rates between the medical therapy and LVRS groups. The
required sample size has been calculated to be 2,500 patients
(ie, 1,250 patients per group).41
The accrual
rate required to reach the target of 2,500 patients in 4.5 years is 2.7
patients per clinic per month. Overall, the trial will have high power
to meet other objectives such as detecting a difference in maximum
exercise capacity (or other continuously distributed random variables).
Analyses
In the initial analysis for any variable, patients will be counted
in the treatment group to which they were randomly assigned without
regard to dropouts, drop-ins, or course of therapy (ie, the
intention-to-treat principle). All events occurring from randomization
on will be counted in the treatment group to which the patient was
randomly assigned. Analyses will be conducted to assess whether any
observed treatment effect is consistent across subsets of patients
(defined by baseline characteristics, eg, age, race, and
gender). Analyses will be conducted separately in the prospectively
defined subset of patients who are thought most likely to benefit. This
approach will be taken for analyses of mortality, complications, and
functional outcomes.
Attempts will be made to define a subset of patients who benefit from treatment (either LVRS or medical therapy). "Benefit" will be defined objectively by a quantitative algorithm based on functional capacity, and all patients will be classified accordingly. The association between benefit and baseline prognostic factors will be assessed using a multiple logistic regression model. The model will be built on a random subset of patients (50%) and validated on the remaining patients. The sensitivity and specificity of the "best" such model will be calculated from the logistic classification method using standard methods. A similar procedure will be used to identify subsets of patients who may be at high short-term risk from treatment. These analyses will be conducted separately in medical and surgical patients, as well as in the combined group.
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Patient Rights and Responsibilities |
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Participation in NETT and Impact on Participation in Transplant
Program
Participation in the trial does not preclude a patient from
undergoing or remaining on the active list for lung transplantation.
Although individual patients may be asked by NETT staff to consider
delaying a transplant at certain times during the protocol, the final
choice will be made by the patient in consultation with their private
physician and will be directed by their clinical situation.
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Conclusion |
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The NETT represents a novel paradigm for evaluating new medical and surgical treatments. The agreement between NHLBI and HCFA to cosponsor NETT specifies that NHLBI will provide scientific and administrative leadership and monitoring (and associated costs) and that HCFA will bear the costs of the clinical services associated with the protocol. The Agency for Health Care Policy and Research contributes support for the cost-effectiveness analysis. NETT could serve as a model for evaluating the benefit and appropriate use of new therapies.
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Appendix: NETT Investigators |
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Clinical Centers
Baylor College of Medicine, Houston, TX:
Rafael Espada, MD
(principal investigator); Joseph Rodarte, MD (co-principal
investigator); Charles Miller, III, PhD (principal clinic coordinator);
Peter Barnard, PhD, RPFT; James Carter, MD; Kimberly DuBose, CRTT;
Tonya Flanigan, RN; Pam Fox, MD; John Haddad, MD, Kathryn Hale, MD;
Everett Hood, RRT; Amy Jahn, RRT; Karen King, RPFT; Chinh Nguyen, RPFT;
Sherl Norman, PTA; Todd Officer, MS; Michael Reardon, MD; Jeannie
Ricketts; Steven Sax, MD; Michael Tucker, RRT; and Kedren Williams.
Brigham and Women’s Hospital, Boston, MA: John Reilly, MD (principal investigator); David Sugarbaker, MD (co-principal investigator); Carol Fanning, RRT (principal clinic coordinator); Karyn Birkenmaier, MS; Simon Body, MD; Carolyn Catanzano, BS; Sabine Duffy, MD; Vladmir Formanek, MD; Anne Fuhlbrigge, MD; Philip Hartigan, MD; Andetta Hunsaker, MD; Francine Jacobson, MD; Linda Mark, BS; Roger Russell, MD; Diane Sauders, MED; Gloria Simons, RN; and Scott Swanson, MD.
Cedars-Sinai Medical Center, Los Angeles, CA: Rob McKenna, MD (principal investigator); Zab Mohsenifar, MD (co-principal investigator); Carol Geaga, RN (principal clinic coordinator); Denise Aberle, MD; Jane Brown, RN, MPH; Susan Clark, RN, MN; Christopher Cooper, MD; Rogel Ferrill, RCPT, RCP; Robert Frantz, MD; Arthur Gelb, MD; Jonathan Goldin, MbChb, PhD, FRCR; Jane Gordon, MA; MFCC; David Head, MD; Milton Joyner, BA; Peter Julien, MD, Michael Levine, MD; Michael Lewis, MD; Marcia Pendio, LCSW; Jeffrey Silverman, MD; Peggy Walker, RRT, RCP; Brenda Williams, BSN, RN; Valentina Yegyan, BS, CPFT; and Charles Yoou, CRTT, CPFT, RCP.
Cleveland Clinic Foundation, Cleveland, OH: Janet Maurer, MD (principal investigator); Malcolm DeCamp, MD (co-principal investigator); Yvonne Meli, RN, C (principal clinic coordinator); Luisa Aviv, LISW; Charles Hearn, DO; Erik Kraenzler, MD; Scott Marlow, RRT; Kevin McCarthy, RCPT; Atul Mehta, MD; Moulay Meziane, MD; Peter O’Donovan, MD; Robert Schilz, DO; and Eugene Sullivan, MD.
Columbia University, New York, NY: Mark Ginsburg, MD (principal investigator); Steven Scharf, MD, PhD (co-principal investigator); Patricia Jellen, MSN, RN (principal clinic coordinator); Asnake Asegu, BS, RRT, RPFT; John Austin, MD; Matthew Bartels, MD; Yahya Berkman, MD; Patricia Berkoski, BS, RRT; Frances Brogan, MSN, RN; Elise Delphin, MD; Glenda Demercado, BSN, RT; Angela DiMango, MD; Lisa DePrisco, BS, CRTT, CPFT; John Gonzales, RT; Jill Gotthelf, BS, CRTT; Peter Herman, MD; Arfa Khan, MD; Mike Mantinaos, MD; Kerri McKeon, BS, RRT, RN; Berend Mets, MD; Gregory Pearson, MD; Jacqueline Pfeffer, MPH, PT; Leonard Rossoff, MD; Arlene Sunshine, MD; Paul Simonelli, MD; Kim Stavrolakes, MS, PT; Byron Thomashow, MD; Denise Vilotijevic, MS, PT; and Chun Yip, MD.
Duke University Medical Center, Durham, NC: Neil MacIntyre, MD (principal investigator); R. Duane Davis, MD (co-principal investigator); John Howe, RN (principal clinic coordinator); Rebecca Crouch, RPT; Katherine Grichnik, MD; David Harpole, Jr, MD; Abby Krichman, RRT; Brian Lawlor; Holman McAdams, MD; Jennifer Norten, PhD; Susan Rinaldo-Gallo, MED; Mark Steele, MD; and Victor Tapson, MD.
Mayo Foundation, Rochester, MN: Rolf Hubmayr, MD (principal investigator); Claude Deschamps, MD (co-principal investigator); Sara Bartling, BA, RN (principal clinic coordinator); Gregory Aughenbaugh, MD; Kristin Bradt; Marlene Edgar, CPFT; Beth Elliott, MD; Eric Edell, MD; James Garrett, BS, RRT, RCP; Karen Hanson, RRT, RCP; Lori Hanson; Gordon Harms, MD; Tom Hartman, MD; Sanjay Kalra, MD; Philip Karsell, MD; David Midthun, MD; Daniel Miller, MD; Carl Mottram, BA, RRT, RPFT; Kari Odenbrett, BS; Stephen Swensen, MD; Anne-Marie Sykes, MD; Norman Torres, MD; and James Utz, MD.
National Jewish Medical and Research Center, Denver, CO: Reuben Cherniack, MD (principal investigator); Barry Make, MD, FACP, FCCP, FAACVPR (co-principal investigator); Mary Gilmartin, BSN, RRT (principal clinic coordinator); Bonnie Buquor, RN; Joyce Canterbury, MED, MSHA; Martin Carlos, BA, RRT; Paul Chetham, MD; Enrique Fernandez, MD; Lisa Geyman, MSPT; David Lynch, MD; John Newell, MD; Marvin Pomerantz, MD; Cynthia Raymond, MS; Beth Safilian, MS; Rickey Tolliver, MPH; Jane Whalen-Price, BS, PT; Kathy Winner, BS, OT; and Martin Zamora, MD.
Ohio State University, Columbus, OH: Philip Diaz, MD (principal investigator); Patrick Ross, MD, PhD (co-principal investigator); Moira Kelsey, RN, MS (principal clinic coordinator); Stephanie Dinant, BS, RRT; Mark King, MD; Ronald Harter, MD; Elisa Mikelinich, RRT; David Rittenger, RRT; and Scott Shaffer, BA.
Saint Louis University, Saint Louis, MO: Keith Naunheim, MD (principal investigator); Cesar Keller, MD (co-principal investigator); Joan Osterloh, RN, BSN (principal clinic coordinator); Francisco Alvarez, MD; Susan Borosh, RRT; Charles Bowen, MD; Sally Frese, RN, MSN; James Glockner, MD; Elisabeth Heiberg, MD; Alan Hibbett, MPH, RPFT; Mary Ellen Kleinhenz, MD; Dinah McCain, PT; Gregg Ruppel, MED, RRT, RPFT; and W. Sherman Turnage, MD.
Temple University, Philadelphia, PA: Gerard Criner, MD (principal investigator); Satoshi Furukawa, MD (co-principal investigator); Anne Marie Kuzma, RN, MSN (principal clinic coordinator); Roger Barnette, MD; Phillip Boiselle, MD; Neil Brester, MD; Gilbert D’Alonzo, DO; Mary Gilmartin, RN, BSN; Michael Keresztury, MD; Linda Kish; Kathy Lautensack, RN, BSN; Edward Leonard, MD; Vadim Leyenson, MD; Madelina Lorenzon, CPFT; Gerald O’Brien, MD; Timothy O’Grady, MD; Peter Rising, MS; Scott Schartel, MD; and John Travaline, MD.
University of California, San Diego, San Diego, CA: Andrew Ries, MD, MPH (principal investigator); Robert Kaplan, PhD (co-principal investigator); Catherine Ramirez, BS, RCP (principal clinic coordinator); Nancy Brewer, AS; Henri Colt, MD; Stephen Crawford, MD; David Frankville, MD; Paul Friedman, MD; Jeffery Johnson, BS; David Kapelanski, MD; Catherine Larsen, MPH; Trina Limberg, BS; Michael Magliocca, RN, CNP; Linda Olson, MD; Frank J. Papatheofanis, MD, PhD; Lela Prewitt; Pamela Resnikoff, MD; and Dawn Sassi-Dambron, RN.
University of Maryland at Baltimore, Baltimore, MD: Mark Krasna, MD (principal investigator); Jonathan Orens, MD (co-principal investigator); Iris Moskowitz, BS (principal clinic coordinator); Michele Altemus, PT; Daniel Bochicchio, MD; E. James Britt, MD; Laura Cook, RN, MS; Henry Fessler, MD; Dino Gaetani; Ileana Gheorghiu, MD; Timothy Gilbert, MD; Jawad Hasnain, MD; Ava Kearney; Sandra Kim, PT; Karen King, CRNP; Susan Markus, RN; Naomi Miller, PT; Ron Schneider; David Shade; Kenneth Silver, MD; Karen Smith; Cynthia Turner, BS; Clarence Weir, BA; Jane Wheeler, MD; and Charles White, MD.
University of Michigan, Ann Arbor, MI: Fernando Martinez, MD (principal investigator); Mark Iannettoni, MD (co-principal investigator); Catherine Meldrum, BSN; RN (principal clinic coordinator); Joy Alexander; William Bria, MD; Kelly Campbell, CPFT; Paul Christensen, MD; Catherine Foss, RPFT; Paramjit Gill, RN; Paul Kazanjian, MD; Ella Kazerooni, MD; Vivian Knieper; Nancy Lowenbergh, RN; Mary Meldrum, RRT; Rebecca Miller; Tammy Ojo, MD; Diana Piergentili; Lewis Poole; Leslie Quint, MD; Paul Rysso, CPFT; Michael Spear, RPFT; Mercedes True, RPFT; and Brian Woodcock, MD.
University of Pennsylvania, Philadelphia, PA: Larry Kaiser, MD (principal investigator); John Hansen-Flaschen, MD (co-principal investigator); Angela Wurster, MSN, CRNP (principal clinic coordinator); Abass Alavi, MD; Theresa Alcorn, BA; Judith Aronchick, MD; Selim Arcasoy, MD; Stanley Aukberg, MD; Bryan Benedict, AAS, RRT; Susan Craemer, BS, RRT, CPFT; Jeffrey Edelman, MD; Warren Gefter, MD; Laura Kotler-Klein, MSS; Robert Kotloff, MD; Scott Manaker, MD, PhD; James Mendez, MSN, CRNP; Wallace Miller, Jr, MD; Wallace Miller, Sr, MD; Harold Palevsky, MD; William Russell, AAS, RPFT; Rodney Simcox, BSRT, RRT; Susanne Snedeker, AAS, RRT, CPFT; and Gregory Tino, MD.
University of Pittsburgh, Pittsburgh, PA: Robert Keenan, MD (principal investigator); Frank Sciurba, MD (co-principal investigator); Elisabeth George, RN, MSN (principal clinic coordinator); Gerald Ayres; Gerene Bauldoff, RN, MSN; Manuel Brown, MD; Philip Costello, MD; Michael Donahoe, MD; Carl Fuhrman, MD; Robert Hoffman, MD; Michael Holbert, MD; Pamela Johnson; Theodore Kopp, MS; Joan Lacomis, MD; Joan Sexton, MS; Laurie Silfies, BS; William Slivka; Diane Strollo, MD; Erin Sullivan, MD; and William Tullock, MD.
University of Washington, Seattle, WA: Joshua Benditt, MD (principal investigator), Douglas Wood, MD (co-principal investigator); Margaret Snyder, MN (principal clinic coordinator); Kymberley Anable; Nancy Battaglia, MS; Louie Boitano, MS; Andrew Bowdle, MD; Leighton Chan, MD; Cindy Chwalik, MS; Bruce Culver, MD; David Godwin, MD; Susan Golden, BS; Andra Ibrahim, MD; Diane Lockhart, BSN; Stephen Marglin, MD; Patricia McDowell; Katrice Nellum; and Gail Van Norman, MD.
Other Participants
Agency for Health Care, Policy and Research, Rockville, MD:
Lynn Bosco, MD, MPH; Yen-Pin Chiang, PhD; Carolyn Clancy, MD; and Harry
Handelsman, DO.
Coordinating Center, The Johns Hopkins University, Baltimore, MD: Steven Piantadosi, MD, PhD (Director); James Tonascia, PhD (co-investigator); Patricia Belt, BS; Karen Collins; Betty Collison; Christopher Dawson; Dawn Dawson; Michele Donithan, MHS; Vera Edmonds; Judith Harle; Rosetta Jackson; Shing Lee, MSc; Charlene Levine, BS; Jill Meinert; Deborah Nowakowski; Daniel Reshef, MD; Michael Smith, BS; Brett Simon, MD; Alice Sternberg, ScM; Mark Van Natta, MHS; and Robert Wise, MD.
Cost Effectiveness Subcommittee: Robert M. Kaplan, PhD (Chair); Yen-Pin Chiang, PhD; Marianne C. Fahs, PhD; A. Mark Fendrick, MD; Alan Jay Moskowitz, MD; Dev Pathak, PhD; Scott D. Ramsey, MD, PhD; Elizabeth Richter, MA; J. Sanford Schwartz, MD; Steven Sheingold, PhD; A. Laurie Shroyer, PhD; Judith Wagner, PhD; and Roger Yusen, MD.
Data and Safety Monitoring Board: John Waldhausen, MD (Chair); Gordon Bernard, MD; David DeMets, PhD; Eddie Hoover, MD; Robert Levine, MD; Donald Mahler, MD; A. John McSweeney, PhD; Jeanine Wiener-Kronish, MD, O. Dale Williams, PhD; and Magdy Younes, MD.
Health Care Financing Administration, Baltimore, MD: Steven Sheingold, PhD; Karen McVearry; Claude Mone; and Joan Proctor-Young.
Office of the Chair of the Steering Committee, University of Pennsylvania, Philadelphia, PA: Alfred P. Fishman, MD (Chair).
Project Office, NHLBI, Bethesda, MD: Gail Weinmann, MD (Project Officer); Joanne Deshler, MS (Contracting Officer); Paul Albert, PhD; Suzanne Hurd, PhD; James Kiley, PhD; and Margaret Wu, PhD
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Footnotes |
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The National Emphysema Treatment Trial is supported by the National Heart, Lung, and Blood Institute, the Health Care Financing Administration, and the Agency for Health Care Policy and Research.
Received for publication June 3, 1999. Accepted for publication July 6, 1999.
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References |
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TOPAbstractIntroductionTerminologyPresent State of Treatment...Surgery for EmphysemaExisting Data on LVRSRationale for the TrialOutcome MeasuresStudy DesignTreatments in the NETTStatistical ConsiderationsPatient Rights and...ConclusionAppendix: NETT InvestigatorsReferences |
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