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Dr. Levine is Associate Professor of Medicine and Medical Director of the Lung Transplant Program, and Dr. Sako is Associate Professor of Surgery and Surgical Director of the Lung Transplant Program, University of Texas Health Science Center at San Antonio and is associated with the South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, San Antonio, TX.
Correspondence to: Stephanie M. Levine, MD, FCCP, The South Texas Veterans Health Care System, Audie L. Murphy Division, Pulmonary Section (111E), 7400 Merton Minter Blvd, San Antonio, TX 78229; e-mail: LEVINES{at}UTHSCSA.EDU
Since lack of donor organs remains the limiting factor to the number of lung transplantation procedures that can be performed, lung transplant physicians and surgeons are struggling constantly to find a balance between those patients who most need this procedure and those who are likely to have a reasonable chance for a favorable outcome. One of the areas that must be addressed in this regard is recipient body weight.
Extrapolating from data in studies from other areas of thoracic surgery, and particularly in the field of cardiac transplantation, one also would suspect that extremes of body weight may portend a worse outcome in the lung transplant recipient.1 2 3 Similar results also have been found in the kidney transplant recipient, with a demonstrated correlation between obesity and increased rates of cardiac disease, and decreased graft and patient survival.4 5 Little has been published on body weight in the field of lung transplantation, other than limited data examining outcomes in cachectic or nutritionally depleted patients who were undergoing lung transplantation. These data suggest that lung transplant recipients with body mass indexes (BMIs) [ie, weight in kilograms divided by the height in meters squared] lower than the 25th percentile, or < 80% of the predicted weight for a certain height, and/or those patients with lean body mass depletion have a worse survival rate following lung transplantation.6 7 8 Additionally, not all studies have reached these same conclusions.9 Until the publication of the article by Kanasky et al in this issue of CHEST (see page 401) and a recent publication by Madill et al,10 no studies had been conducted on the opposite extreme (ie, the evaluation of a morbidly obese patient for lung transplantation). Other problems that have been seen in the few studies on the extremes of body weight have been the variable definitions of obesity and the interchangeable use of measures of BMI and percentage of ideal body weight.
A decade ago, as newcomers to this field, a new possible transplant recipient would be presented (including information on height and weight) to our then-surgical director of the lung transplant program (and one of the pioneers in lung transplantation) Dr. J. Kent Trinkle. Often, it was a patient who, in the pulmonologists’ minds, was only moderately overweight. After completing the presentation, Dr. Trinkle would respond, "the only problem with that patient is that he or she is several inches too short!" The article presented in this issue lends support to the surgical concerns about performing transplants in overweight patients. Further experiences in this field over the past decade, have reinforced the opinions of our surgical colleagues.
In 1997, a group of transplant physicians and surgeons representing multiple transplant-related organizations convened to establish guidelines for lung transplant recipients. Although few studies had clearly examined the impact of body weight on outcomes following lung transplantation, this group suggested that extremes of ideal body weight < 70% and > 130% should be relative contraindications to lung transplantation. However, it should be emphasized that these numbers were established purely by consensus.11
The guidelines regarding obesity were extrapolated from cardiothoracic dogma, which indicated that obesity results in a technically more difficult surgical procedure. Obesity is known to decrease respiratory system compliance, due to increased weight on the thoracic cage and abdomen, and increased respiratory muscle demand, which leads to an increase in the level of oxygen consumption required for the work performed.12 13 In addition, obesity can change the relationships among the mechanics of the lung parenchyma, the chest wall, and the diaphragm. Impaired gas exchange can result in eventual cardiopulmonary complications. Obesity also can be a risk factor for wound infection and dehiscence, thrombophlebitis, and abnormalities in drug pharmacokinetics and distribution. The concerns regarding underweight individuals, particularly those with cystic fibrosis, are that they may be too disabled and cachectic to perform adequate rehabilitation and to gain weight in the posttransplantation period, and also may be at increased risk for infection. Thus, there is the impression that extremes of body weight correlating with a poor outcome following lung transplantation are based on very little scientific evidence and are, in fact, primarily based on clinical experience.
Since selection often is based on institutional clinical experience, we read with great interest the article by Kanasky et al in this issue of CHEST. The article reports a single-institution, longitudinal, retrospective examination for the determination of the impact of pretransplantation BMI on posttransplant survival time. The authors examined a study population of 85 patients at a single transplant center from 1994 to 1998. The investigators used both univariate and multivariate analyses to study the impact of BMI on posttransplant survival time. The patients were divided into the following four groups, as defined by the revised World Health Organization and National Institutes of Health guidelines in 1998: underweight (BMI, < 18.5); normal weight (BMI, 18.5 to 24.9); overweight (BMI, 25 to 29.9); and obese (BMI, > 30).14 15 Each study group was small with a short follow-up period (range, 1 to 74 months), but unfortunately, this is the norm for clinical studies in patients who have undergone lung transplantation.
The authors were able to draw several conclusions from their study. They found, as we have observed at our own center, that obese patients have poorer survival rates following lung transplantation (perhaps as high as a three times greater mortality rate) than did nonobese patients, exclusive of the underlying disease process. Furthermore, the authors concluded that nonobese overweight and underweight patients do not necessarily do poorly following lung transplantation, as has been suggested.7 8
There are several questions that were left unanswered in the study. First, it is unclear why, given the stated institutional selection criteria, 10 patients with this degree of obesity underwent transplantation at this center. Were there other factors contributing to the selection of these patients? Also, it is not clear whether the BMI was determined at the time of placement on the transplantation list or at the time of transplantation. Perhaps obese patients underwent transplantation because of the correlation differences between the measurements of ideal body weight and BMI. Due to the short follow-up period and the small number of obese patients (n = 10), it was not clear from the study why the survival rate was poorer in the obese group (ie, was the incidence of nontransplant-related complications such as cardiac events increased in this group?). The authors state that there was no observed difference between freedom from obliterative bronchiolitis in the obese or nonobese recipients. Furthermore, the incidence of infection was not different between the groups. The authors speculate that perhaps the inability of the obese patient to sustain the increase in respiratory workload required during graft complications could be a contributing cause of reduced survival time.
Another interesting observation from this study was the superior survival curve of underweight patients in the first 50 months after they had undergone transplantation, followed by a noticeable decrease. This is contrary to what one would expect, namely, that underweight patients would have more difficulties in the immediate postoperative period. It would be important to observe the changes in weight in the posttransplant period, given the effects of corticosteroid therapy and, in the case of the underweight patients, improved nutritional status.
Recently, another article10 reached similar conclusions with regard to obesity. In this retrospective, single-center study, patients with extremes of obesity also were found to have poorer outcomes, including survival time and prolonged length of stay in the ICU in the first 90 days following lung transplantation. These authors used similar, but not identical, BMI categories as were used in the study by Kanasky et al. They defined the highest BMI group as having a BMI > 27. This study found a trend toward a higher mortality rate in the cachectic group (BMI, < 17) and in the overweight group (BMI, 25 to 27), in contrast to that found in the study by Kanasky et al.
What should be gleaned from these articles? Should this information be used to establish strict body mass criteria for determining lung transplantation candidacy at a time when recipient waiting times are exorbitant and donor shortage remains a significant problem? Should we be giving the limited number of organs to patients who are obese and, thus, are expected to have a poorer outcome based on the information in these articles? These are difficult questions since we all have encountered patients with end-stage lung disease who fall into either of these two extremes. For example, the obese primary pulmonary hypertensive patient who may have acquired his or her lung disease from pharmacologic agents used for weight reduction and who have not responded to vasodilator therapy. What about the obese COPD patient who desaturates too much to perform anything but minimal exercise and certainly cannot exercise to lose weight? In contrast, there are the cachectic cystic fibrosis patients who, despite adequate nutrition and sometimes the use of enteral feeding tubes or total parenteral nutrition, cannot gain weight because of their malabsorption and high work of breathing. Should these patients be denied transplantation?
Clearly, further larger studies need to be performed in this area to elucidate the specifics of the poor outcomes in obese patients and to address some of these questions. Finally, this article leads one to entertain various options for evaluating a potential lung transplant candidate who meets the medical criteria for lung transplantation, yet falls into an extreme category of BMI. One approach would be to deny a lung transplant evaluation for these patients. Another approach might be to determine a target weight at which the patient could begin the evaluation for lung transplantation. Some lung transplant programs have instituted weight-management programs to assist with the weight loss.16 Yet, a fourth choice might be to proceed with transplantation listing with the documentation of continued weight loss required. At our center, we have chosen this last approach.
As always, the issues raised are provocative ones for the field of lung transplantation. Collecting the experience of other centers, or preferably performing a cooperative study, would be helpful in further elucidating this "weighty" issue.
References
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