Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (11)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Butler, C. W.
Right arrow Articles by Benditt, J. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Butler, C. W.
Right arrow Articles by Benditt, J. O.
(Chest. 2001;119:1056-1060.)
© 2001 American College of Chest Physicians

Underestimation of Mortality Following Lung Volume Reduction Surgery Resulting From Incomplete Follow-up*

Charles W. Butler, BA; Margaret Snyder, RN, MSN; Douglas E. Wood, MD, FCCP; J. Randall Curtis, MD, MPH; Richard K. Albert, MD, FCCP and Joshua O. Benditt, MD, FCCP

* From the Departments of Medicine and Surgery (Mr. Butler, Ms. Snyder, and Drs. Wood, Curtis, and Benditt), University of Washington, Seattle, WA; and Medical Service (Dr. Albert), Denver Health Medical Center, and Department of Medicine, University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Joshua O. Benditt, MD, FCCP, Respiratory Care Services, University of Washington Medical Center, Pulmonary and Critical Care Medicine, Box 356522, Seattle, WA 98195-6522


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: Incomplete follow-up can bias interpretation of data that are collected in longitudinal studies. We noted that many patients failed to return for follow-up in a study of effect of lung volume reduction surgery (LVRS) on quality of life (QOL). Accordingly, we designed this investigation to determine the reasons patients dropped out, and to assess differences between those who continued in the study (attendees) and those who did not (nonattendees).

Design: Telephone survey.

Subjects: Patients with advanced emphysema who had undergone LVRS and had previously agreed to participate in a longitudinal QOL study.

Results: No differences were found with regard to age, gender, preoperative pulmonary function, or oxygen use between attendees and nonattendees. Long-term mortality in nonattendees (27%) was considerably greater than that seen in attendees (3%, p < 0.05). Distance from the hospital, financial burden, and living out of the region were the most common reasons cited by surviving nonattendees for their failure to return for follow-up.

Conclusions: Studies reporting the long-term mortality after LVRS can be biased in the direction of underestimating the true value if they are compromised by incomplete follow-up.

Key Words: lung volume reduction surgery • mortality study design • survival


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Lung volume reduction surgery (LVRS) increases expiratory airflow, maximum exercise capacity, respiratory muscle strength, elastic recoil, and improves the PaCO2, ventilatory muscle recruitment pattern, and the sensation of dyspnea in patients with emphysema.1 2 3 4 5 6 7 8 9 Since its reintroduction in 1994,2 the results of observational studies3 10 11 12 13 14 15 16 17 18 19 20 designed to evaluate changes in lung function and quality of life (QOL) for patients undergoing this procedure have been encouraging. As several authors note, however, most of these studies are limited by relatively small numbers of patients as well as by incomplete follow-up rates that have ranged from 5 to 60%.12 13 14 15 16 17 18 19 20 21 22 23 Data from a number of longitudinal studies in other settings indicate that results can be biased by the problem of incomplete follow-up if there are differences between patients who continue in the study and patients who do not.23 24 25 26

In March 1995, the University of Washington Medical Center (UWMC) initiated a longitudinal QOL study for patients undergoing LVRS. After 18 months, we noted that 60% of the subjects had missed more than two consecutive follow-up appointments, despite receiving both written and telephone reminders. This high dropout rate led us to ask (1) why patients failed to return for their follow-up appointments, and (2) if any differences could be found that might explain why some returned and others did not.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The goal of the original QOL study was to compare changes in lung function after LVRS with QOL assessment over time. Patients were initially interviewed a maximum of 4 weeks before their LVRS, and were to be reassessed at 3 months, 6 months, 12 months, 18 months, and 24 months after their operation. The Institutional Review Board of the University of Washington approved the study. Participation in the study was not a requirement for having LVRS at the UWMC.

The study protocol and the frequency of follow-up required were carefully and thoroughly explained to each patient during his or her initial visit. Each patient was contacted by telephone at the appropriate intervals and instructed to schedule his or her follow-up appointments. A written reminder was then sent.

For purposes of the present nonattendance study, individuals who failed to attend two consecutive appointments, or indicated that they no longer wanted to participate in the QOL study, were defined as nonattendees. All others were defined as attendees.

We attempted to contact all patients in the attendee and nonattendee groups by telephone over a 2-week period at the conclusion of the QOL study. At the time of contact, a median of 26 months (range, 7 to 35 months) had elapsed since LVRS. The status of patients whose telephone had been disconnected or whose telephone number had been changed was investigated further by contacting their referring physician or their family. The names of patients whose survival status was still not known were then checked against state death registries.

Attendees and all of the nonattendees who were contacted were asked an open-ended question, "What were the reasons why you did not return to the medical center for the LVRS study follow-up?" If the subject gave more than one reason, he or she was asked to rank each in the order of their importance. The subject was then presented with 12 investigator-identified reasons that might have contributed to his or her nonattendance and asked to confirm or deny whether each contributed to his or her nonattendance. They were then asked to rank these in decreasing importance.

The driving distance from the subject’s hometown to the UWMC was determined using the Rand McNally Transcontinental Mileage Driving Map (Rand-McNally; Skokie, IL).

The patient’s primary-care physician determined oxygen use both before and after surgery.

Statistical Analysis
Mortality rates and oxygen use in the two groups were compared using Fisher’s Exact Test. Pulmonary function tests were analyzed using Student’s t test. Gender difference was sought using a Pearson’s {chi}2 test, and the Mann-Whitney test was used for assessing differences in driving distances. All statistical analyses were conducted using the Statistical Package for Social Sciences (Version 7.5; SPSS; Chicago, IL)


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Patient Characteristics
Between March 1995 and August 1997, the end of the enrollment period, 135 patients underwent LVRS at the UWMC. Seven of the 135 patients (5%) died in the first 30 days after surgery. Ninety-one patients consented to participate in the QOL study. Six patients died before their first follow-up appointment. Accordingly, 85 patients were available to participate in the nonattendance study. Their demographic data are summarized in Table 1 .


View this table:
[in this window]
[in a new window]

  		Table 1. Population Characteristics Prior to LVRS*

 
Major comorbidities for study subjects are shown in Table 2 . The total number of major comorbidities was significantly higher in the nonattendee group.


View this table:
[in this window]
[in a new window]

  		Table 2. Major Comorbidities for Nonattendees and Attendees*

 
Table 3 reports pulmonary function test results in the attendees before and after LVRS. Clinically and statistically significant increases in FEV1 and FVC, and decreases in TLC and residual volume were seen.


View this table:
[in this window]
[in a new window]

  		Table 3. Pulmonary Function Test Results in Attendees Before and After LVRS*

 
Mortality
Thirty-two of the 51 nonattendees (63%) were contacted by telephone (Table 4 ). Additional investigation of the 19 who could not be reached revealed that 14 patients (27% of the 51) had died some time after they had refused follow-up. We were unable to contact five nonattendees (10%), and their status remained unknown. Of the 34 attendees, 31 were contacted (91%). Only one attendee (3%) had died. Two attendees were unreachable (6%), and their status is unknown. The mortality rate was higher in the nonattendee group (27% vs 3%, p < 0.05). Figure 1 describes the cumulative survival in both groups. The median time from surgery to death in nonattendees was 18 ± 3 months. The one attendee death occurred 36 months after LVRS.


View this table:
[in this window]
[in a new window]

  		Table 4. Mortality

 


View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Cumulative survival rates, with Kaplan-Meier curve for attendees and nonattendees. For graphical presentation clarity only, the one attendee who died at 36 months was censored immediately before death. The death of this individual was used in the statistical analysis.

 
We also analyzed the data assuming that all of the nonattendees we were unable to contact were alive, and that all attendees we were unable to contact had died. The mortality difference between the two groups was still different (27% vs 9%, p < 0.05).

Reasons for Nonattendance
Responses by surviving nonattendees to the open-ended question about reasons for nonattendance varied. Those cited most commonly were distance from the medical center, personal issues (eg, divorce, loss of a family member), and the need for a social support system that could assist with transportation and with preparing the patient for travel.

The travel time and effort involved with keeping appointments were the most commonly cited investigator-selected reasons for nonattendance (Fig 2 ). The average driving distance from home to the UWMC was 203 miles for nonattendees and 52 miles for attendees (p < 0.05).



View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Reasons cited for nonresponse, and the number of times a reason was cited as being moderately important to very important in a decision not to return to UWMC for follow-up.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The most important finding of our study was that subsequent to the time that patients chose to drop out of the longitudinal follow-up study of the effects of LVRS on QOL, their mortality rate was 10-fold higher than those who continued to be seen. It is important to emphasize that all of the deaths in the nonattendee group occurred after nonattendance was established, that is, death was not the reason for their failure to follow-up.

We looked for but found no differences in preoperative pulmonary function between attendees and nonattendees, but our study was not powered to detect small, but potentially important differences in these variables. Our data may not accurately reflect the true long-term mortality rates in the two groups because we were only able to determine the survival status in 94% and 91% of the attendees and nonattendees, respectively. Assuming the maximum bias, however (ie, that all nonattendees who were not contacted survived, and that all attendees not contacted had died), we still found that the mortality rate in the nonattendees was higher.

Most of the published studies of LVRS are either case series or present longitudinal follow-up of patients who have undergone the procedure; dropout rates in these studies have ranged from 5 to 60%.12 13 14 15 16 17 18 19 20 Our data suggest that these studies could be biased in the direction of suggesting a more favorable outcome of LVRS in terms of mortality and perhaps the effect of surgery than might be the case. Preliminary data from Hamacher and colleagues27 support this suggestion, as they found that patients who failed to follow-up after LVRS were less likely to benefit from the procedure. Preliminary data from Brenner et al28 also included a concern for dropout bias after LVRS.

Failure to follow-up (nonattendance) is a well-documented problem in longitudinal studies and can introduce important bias.23 24 25 26 The Framingham study25 reported that 31% of screened patients did not return for their first follow-up appointment and that, over the course of the study, another 13% dropped out. Nonattendance is associated with the sickest patients enrolled in studies. Wilhelmsen and colleagues29 noted that nonattendance is associated with serious comorbidities such as advanced age, poor performance on the mini-mental status test, alcoholism, and chronic disease. We found a higher incidence of serious comorbidities in our nonattendees when compared with attendees. We believe that there are two possible reasons for nonattendance in the deceased nonattendees: (1) comorbidities added to the difficulties of the subjects returning to our center for follow-up, or (2) nonattendees experienced less benefit from LVRS and were therefore less inclined to return for further evaluation. Our study cannot differentiate between these two possibilities. Regardless, it is clear that attendees and nonattendees in our study have substantially different clinical outcomes.

The most common reason given for dropout by our surviving nonattendees was distance away from the medical center. Emphysema is a debilitating disease. Oxygen and other assistive devices needed by these patients are cumbersome and make all types of travel more difficult. The average distance from the medical center for the nonattendees was almost four-times greater than for the attendees. This problem is magnified at the University of Washington, as we see referrals from five states, covering an area of several thousand square miles.

The results of our study demonstrate the importance of considering the effect of incomplete follow-up on data acquired in longitudinal studies of LVRS. Bias toward more favorable outcomes may occur when dropout rates are high (as has been the case with most studies of LVRS to date). Our findings also suggest that the participation of patients with COPD (and perhaps those with a number of other debilitating conditions) in longitudinal studies might be improved by making special provisions aimed at easing the difficulties traveling to and from follow-up appointments, particularly when these occur at distant centers.


   Footnotes
 
Abbreviations: LVRS = lung volume reduction surgery; UWMC = University of Washington Medical Center; QOL = quality of life

Received for publication October 7, 1999. Accepted for publication October 6, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Brantigan, O, Mueller, E (1957) Surgical treatment of pulmonary emphysema. Am Surg 23,789-804[Medline]
  2. Cooper, JD, Trulock, EP, Triantafillou, AN, et al (1995) Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. Thorac Cardiovasc Surg 109,106-116
  3. Daniel, TM, Chan, BB, Bhaskar, V, et al (1996) Lung volume reduction surgery: case selection, operative technique, and clinical results. Ann Surg 223,526-531[CrossRef][ISI][Medline]
  4. Gelb, AF, McKenna, RJ, Jr, Brenner, M, et al (1996) Contribution of lung and chest wall mechanics after emphysema resection. Chest 110,11-17[Abstract/Free Full Text]
  5. Naunheim, KS, Ferguson, MK (1996) The current status of lung volume reduction operations for emphysema. Ann Thorac Surg 62,601-612[Abstract/Free Full Text]
  6. Sciurba FC, Rogers RM, Keenan RJ, et al. Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema. N Engl J Med 1996; 25:334: 1095–1099
  7. Benditt, JO, Wood, D, McCool, FD, et al (1997) Changes in breathing and ventilatory muscle recruitment patterns induced by lung volume reduction surgery. Am J Respir Crit Care Med 155,279-284[Abstract]
  8. Benditt, JO, Lewis, S, Wood, DE, et al (1997) Improvements in maximum O2 consumption, minute ventilation, O2 pulse and deadspace during cycle ergometry after lung volume reduction surgery. Am J Respir Crit Care Med 156,561-566[Abstract/Free Full Text]
  9. Albert, RK, Benditt, JO, Hildebrandt, J, et al (1998) Lung volume reduction surgery has variable effects on blood gases in patients with emphysema. Am J Respir Crit Care Med 158,71-76[Abstract/Free Full Text]
  10. Cordova, F, O’Brien, G, Furukawa, S, et al (1997) Stability of improvements in exercise performance and quality of life after bilateral lung volume reduction surgery in severe COPD. Chest 112,907-915[Abstract/Free Full Text]
  11. Criner, GJ, OBrien, G, Furukawa, S, et al (1996) Lung volume reduction surgery in ventilator-dependent COPD patients. Chest 110,877-884[Abstract/Free Full Text]
  12. Little, AG, Swan, JA, Nino, JJ, et al (1995) Reduction pneumoplasty for emphysema: early results. Ann Surg 222,365-371[ISI][Medline]
  13. McKenna, RJ, Jr, Brenner, M, Mullin, M, et al (1996) A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. Thorac Cardiovasc Surg 111,317-322
  14. Hazelrigg, S, Boley, T, Henkle, J, et al (1996) Thoracoscopic laser bullectomy: a prospective study with 3-month results. Thorac Cardiovasc Surg 112,319-326
  15. Cooper, JD, Patterson, GA, Sundaresan, RS, et al (1996) Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema. Thorac Cardiovasc Surg 112,1319-1330
  16. Miller, JI, Jr, Lee, RB, Mansour, KA (1996) Lung volume reduction surgery: lessons learned. Ann Thorac Surg 61,1464-1468[Abstract/Free Full Text]
  17. Daniel, TM, Chan, BBK, Bhaskar, V, et al (1996) Lung volume reduction surgery: case selection, operative technique and clinical results. Ann Surg 223,526-533
  18. Keenan, RJ, Landreneau, RJ, Sciurba, FC, et al (1996) Unilateral thoracoscopic surgical approach for diffuse bullous emphysema. Thorac Cardiovasc Surg 111,308-316
  19. Wakabayashi, A (1995) Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema. Ann Thorac Surg 60,936-942[Abstract/Free Full Text]
  20. Keenan, RJ, Sciurba, FC, Landreneau, RJ, et al (1996) Superiority of bilateral versus unilateral thoracoscopic approaches to lung reduction surgery [abstract]. Am J Respir Crit Care Med 153,A268
  21. McKenna, RJ, Brenner, M, Fischel, RJ, et al (1996) Should lung volume reduction surgery for emphysema be unilateral or bilateral? Thorac Cardiovasc Surg 112,1331-1338
  22. Utz, JP, Hubmayr, RD, Deschamps, C (1998) Lung volume reduction surgery for emphysema: out on a limb without a NETT. Mayo Clin Proc 73,552-566[ISI][Medline]
  23. Fessler, HE, Wise, RA (1999) Lung volume reduction surgery: is less really more? Am J Respir Crit Care Med 159,1031-1035[Free Full Text]
  24. Gordon, T, Moore, FE, Shurtleff, D, et al (1959) Some methodologic problems in the long-term study of cardiovascular disease: observations on the Framingham Study. J Chronic Dis 10,186-206[CrossRef]
  25. Burg, J, Allred, S, Sapp, J (1997) The potential for bias because of attrition in the national exposure registry: an examination of reasons for nonresponse, nonrespondent characteristics and the response rate. Toxicol Ind Health 13,1-13[ISI][Medline]
  26. Greenland, S (1977) Response and follow-up bias in cohort studies. Am J Epidemiol 106,184-187[Free Full Text]
  27. Hamacher, J, Stammberger, U, Bloch, KE, et al (1999) Loss of follow-up after bilateral thoracoscopic lung volume reduction surgery [abstract]. Am J Respir Crit Care Med 159,A824
  28. Brenner, M, McKenna, RJ, Chen, JC, et al (1999) Survival after bilateral staple lung volume reduction surgery for emphysema. Chest 115,390-396[Abstract/Free Full Text]
  29. Wilhelmsen, L, Ljungberg, S, Wedel, H, et al (1976) A comparison between participants and non-participants in a primary preventive trial. J Chronic Dis 29,331-339[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
P. H. Schipper, B. F. Meyers, R. J. Battafarano, T. J. Guthrie, G. A. Patterson, and J. D. Cooper
Outcomes after resection of giant emphysematous bullae
Ann. Thorac. Surg., September 1, 2004; 78(3): 976 - 982.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
P. E. Munro, M. J. Bailey, J. A. Smith, and G. I. Snell
Lung Volume Reduction Surgery in Australia and New Zealand: Six Years On: Registry Report
Chest, October 1, 2003; 124(4): 1443 - 1450.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
S. S. Pakhale, C. Gutierrez, S. Piantadosi, A. Fishman, and the National Emphysema Treatment Trial Research Gr
Lung-Volume-Reduction Surgery
N. Engl. J. Med., September 4, 2003; 349(10): 999 - 1000.
[Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
A. M. Ciccone, B. F. Meyers, T. J. Guthrie, G. E. Davis, R. D. Yusen, S. S. Lefrak, G. A. Patterson, and J. D. Cooper
Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema
J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(3): 513 - 525.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
E. Pompeo and T. C. Mineo
Long-term outcome of staged versus one-stage bilateral thoracoscopic reduction pneumoplasty
Eur. J. Cardiothorac. Surg., April 1, 2002; 21(4): 627 - 633.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
National Emphysema Treatment Trial Research Group
Patients at High Risk of Death after Lung-Volume-Reduction Surgery
N. Engl. J. Med., October 11, 2001; 345(15): 1075 - 1083.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (11)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Butler, C. W.
Right arrow Articles by Benditt, J. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Butler, C. W.
Right arrow Articles by Benditt, J. O.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS