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Editorial
10.1586/ERS.09.62
Should weight be a criterion for lung
transplant selection?
Expert Rev. Resp. Med. 4(1), 1–3 (2010)
…a significant number of patients die while waiting for a lung
transplant because of a lack of available organs.
Denis Hadjiliadis,
MD, MHS, FRCP(C),
FCCP
Assistant Professor of
Medicine, Division of
Pulmonary, Allergy and
Critical Care, University
of Pennsylvania, PA,
USA
and
Director, Adult Cystic
Fibrosis Program,
Associate Medical
Director, Lung
Transplantation
Program, 835W Gates
Building, Hospital of the
University of
Pennsylvania, 3600,
Spruce Street,
Philadelphia, PA 19104,
USA
Tel.: +1 215 615 3871
Fax: +1 215 662 3226
denis.hadjiliadis@
uphs.upenn.edu
hadjiliadisdenis@
hotmail.com
Lung transplantation is considered an
acceptable treatment option for end-stage
lung disease. The number of transplants
performed has continued to increase over
the years, reaching 2708 procedures world-
wide [1] and 1465 in the USA during 2007
[2]. However, lung transplant outcomes
remain inferior to other solid organ trans-
plants with 1-year survival rates of 79%
and 5-year survival rates of 52% [1]. In
addition, a significant number of patients
die while waiting for a lung transplant
owing to a lack of available organs [2]. The
number of waiting list deaths in the USA
improved initially with the new lung alloca-
tion score and the donor increase initiative,
but has now reached a plateau [2]. Therefore,
it remains very important to select patients
that have the best chance of survival after
lung transplantation, to appropriately
allocate this precious resource.
According to the most recent guidelines
by the International Society for Heart and
Lung Transplantation, obesity is a relative
contraindication to lung transplantation [3] .
Obesity prevalence in the USA has dra-
matically increased over the last 15 years
[101]. Using a definition of BMI above
30 kg/m2, only one state in 2008 had a
prevalence of obesity less than 20%, while
six states had a prevalence of more than
30%. By contrast, in 1994 all 50 states
had an obesity prevalence of less than 20%
according to data from the CDC [101] . As
a result of this rise in obesity, there is a
significant increase in the number of obese
patients requiring the provision of multi-
ple healthcare services and clinicians fre-
quently face questions on the appropriate
management of these patients. These ques-
tions and dilemmas are likely to intensify
over the next 5–10 years. Some patients
with end-stage lung disease are at par-
ticular risk of obesity owing to steroid use
(e.g., patients with idiopathic pulmonary
fibrosis [IPF]).
Most recent reports suggest that the
effect of obesity is small on survival out-
comes. In cardiac surgery, obesity leads to
a small but significant increase in mortal-
ity [4] and wound infections [5]. In other
solid organ transplants, there are conflict-
ing data on the effect of obesity on post-
transplant outcomes; most suggest that
these patients have worse outcomes [6–8] ,
and almost all of the studies have suggested
increased post-transplant complications.
In addition, all the aforementioned have
mainly considered patients with extreme
obesity (BMI >35, or even 40 kg/m2).
Obesity prevalence in the USA
has dramatically increased over
the last 15 years.
In lung transplantation there are few
studies that have attempted to address the
question. Two early single-center studies
suggested that increased weight was asso-
ciated with increased mortality after lung
transplantation. In the first, a BMI above
27 was associated with increased 90-day
mortality [9]. In the second study, a very
small number of obese (BMI >30 kg/m2)
patients had significantly increased mor-
tality [10]. Both studies reported patients
that were mainly tra nsplanted in the
1990s. These studies were followed by
a larger single-center study that sug-
gested increased weight had no effect
on post-transplant outcomes, other than
slightly increased 90-day mortality [11] .
Furthermore, that center originally used
ideal body weight (IBW) as a selection
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Expert Rev. Resp. Med. 4 (1), (2010)
2
Editorial
criterion for lung transplantation and a group of patients that
were originally misclassified as normal weight (but actually had
an increased IBW) had no different survival compared with
normal-weight patients [11].
More recently, we reviewed outcomes of obese patients trans-
planted in our center in the last 4 years; data has only been pre-
sented at an international meeting to date [12]. Obese patients
had similar outcomes despite an increased percentage of patients
with IPF and increased rates of coronary disease, which would
tend to increase the mortality of these patients. Further analy-
ses are underway. Data from the International Registry does not
shed adequate light on this problem. BMI has occasionally been
a risk factor for post-transplant outcomes, but in the most recent
registry report, individual components of BMI (recipient weight
for emphysema and IPF patients predicted 1-year mortality, while
recipient height predicted 5-year mortality) were predictors of
survival, but not BMI itself [1].
Lederer et al. recently published the most comprehensive study
on the subject to date. It included data from the USA (United
Network for Organ Sharing region) from 1995 to 2003. Data were
reported after an extensive multivariable ana lysis of many risk
factors affecting post-transplant outcomes. Overall, a BMI over
30 kg/m2 was associated with an approximately 30% increased
risk of post-transplant mortality [13]. These findings remained sig-
nificant when only patients with chronic obstructive pulmonary
disease and IPF were analyzed as a single group. Overall, obesity
accounted for 12% of deaths in the first year post-transplant (if
one assumes 1-year survival of 82%, obesity accounts for an ~2%
change in survival). The main limitation of the study is that it
included a large era of lung transplantation, when practices might
have evolved and obesity rates might have changed.
As a higher percentage of the population is
becoming obese, obese patients are now healthier
and can undergo major procedures successfully.
In summary, the aforementioned data suggests the following
possibilities. Most likely, obesity confers a slightly increased risk of
poor outcome after lung transplantation and the effect of obesity
at individual centers is magnified or reduced owing to the small
number of patients in the respective studies. Another explanation
for the disparate findings might be differences in obese patients in
the earlier and later years. As a higher percentage of the population is
becoming obese, obese patients are now healthier and can undergo
major procedures successfully. Healthcare teams at different centers
might also be learning how to better treat obese patients, so that the
outcomes are similar to patients without obesity. Finally, different
centers might truly have different outcomes for obese patients owing
to different surgical techniques. For example, our center frequently
uses median sternotomy for obese patients, and this might lead to
decreased pain and therefore better outcomes for these patients.
However, this has not been studied extensively to date.
In any case, obesity confers a small risk of poor post-transplant
outcomes and therefore it should be taken into account together
with the overall condition of the recipient, the course of the
underlying disease and other risk factors the patient might have
for poor outcome with or without a transplant. Obesity should be
a smaller factor in deciding whether listing for lung transplanta-
tion is appropriate or not, compared with other contra indications,
such as mechanical ventilation and colonization with bacteria
such as Burkholderia cepacia [1,3]. Nevertheless, every effort should
be made to achieve a normal body weight from the time of evalu-
ation to transplantation, since this is one of the few modifiable
risk factors patients with end-stage lung disease might have. In
addition, other diseases that are associated with obesity (e.g.,
diabetes mellitus, hypertension and coronary disease) should be
aggressively worked up and treated.
In any case, obesity confers a small risk of poor
post-transplant outcomes and therefore it should
be taken into account together with the overall
condition of the recipient, the course of the
underlying disease and other risk factors the
patient might have for poor outcome with or
without a transplant.
We expect to see an increased number of obese patients over
the next 5–10 years and careful study of these patients is war-
ranted in order to provide them with the best possible treatment
options, without excluding them from a potentially life-saving
procedure; however, patients with consistently poor outcomes
should not receive this precious and scarce resource. Further
studies using the most recent data need to be undertaken. In
view of the small effect of obesity on outcomes, few select cent-
ers should consider undertaking the study of patients with a
BMI over 35 or even 40 kg/m2, since most of these patients are
excluded from lung transplantation.
Another aspect of the issue of obesity and lung transplanta-
tion is an adequate way to measure forms of obesity that confer
increased risk of poor outcomes. Many centers are in the process of
assessing other parameters; for example, fat-free mass in addition
to BMI in lung transplant candidates. The results of these studies
might provide a better way to assess pretransplant obesity. It might
also help to explain the small effect of obesity in outcomes based
on the current studies.
Referring physicians should consult with lung transplant centers
when sending patients to these centers and, if the main reason for
exclusion from transplant is obesity, opinions from other centers
should be asked. Hopefully, in the next 5–10 years we will have
enough data to identify those obese patients who can safely receive
lung transplant, expect to benefit from the procedure and have
prolonged survival with improved quality of life.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Hadjiliadis
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Editorial
References
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Should weight be a criterion for lung transplant selection?
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Chapter
Selection criteria for lung transplantation have evolved significantly over the last 3 decades and there are few absolute contraindications. A number of relative contraindications exist but most can be managed effectively given early referral, depending on the experience of the individual transplant unit. Effective communication between the referral source and the transplant unit is crucial to enable optimum outcomes. Successful lung transplantation is built on team work and each craft group plays a critical role in achieving the best results. This chapter will outline the key developments which have led to the current position regarding selection criteria and show the chronology of approach. Given that key consensus documents exist to guide referral and selection of potential candidates this particular chapter will attempt to analyze the body of work which underpins those decisions and show how the global lung transplant community has worked cohesively to improve outcomes for patients who might benefit from their services.
Article
Full-text available
Obesity is considered a relative contraindication to lung transplantation, based on studies that have not accounted for key confounders. Little is known about the risk of death for underweight candidates after transplantation. To examine the associations of pretransplant obesity and underweight with the risk of death after lung transplantation. We examined 5,978 adults with cystic fibrosis, chronic obstructive pulmonary disease, and diffuse parenchymal lung disease who underwent lung transplantation in the United States between 1995 and 2003. We used Cox models and generalized additive models to examine the association between pretransplant body mass index and the risk of death after lung transplantation with adjustment for donor and recipient factors. The median follow-up time was 4.2 years. Compared with normal weight recipients, the multivariable-adjusted rates of death were 15% higher for underweight recipients (95% confidence interval, 3 to 28%), 15% higher for overweight recipients (95% confidence interval, 6 to 26%), and 22% higher for obese recipients (95% confidence interval, 8 to 39%). These relationships persisted when stratified by diagnosis. The multivariable-adjusted population attributable fraction was 12% at 1 year and 8% at 5 years. Both obesity and underweight are independent risk factors for death after lung transplantation, contributing to up to 12% of deaths in the first year after transplantation. Primary care providers and pulmonologists should promote a healthy weight for patients with lung disease long before transplantation is considered.
Article
Study objectives The purpose of this study was to determine the impact of a pretransplantation determination of body mass index (BMI) on survival after lung transplantation. Design and patients Univariate and multivariate survival analyses of a single institution database consisting of 85 patients who had undergone lung transplantations between March 1994 and October 1998. Setting University of Florida Health Science Center. Results Kaplan-Meier survival curves showed that patients who were obese (ie, BMI, ≥30) at a pretransplantation assessment had a marked decrease in posttransplantation survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression model revealed that the most powerful predictors of mortality after lung transplantation were higher pretransplantation BMI and the development of obliterative bronchiolitis. Conclusions Our results suggest that the posttransplantation risk for mortality is possibly three times greater for obese patients than for nonobese patients. Additional study is needed to identify the mechanisms for such higher risk in obese patients. Our data also suggest that transplantation centers should not routinely reject underweight patients (ie, BMI,< 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung transplantation listing solely on the basis of weight, as their outcomes may not be significantly different than patients with normal BMIs.
Article
This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.
Article
We investigated the impact of extreme obesity (body mass index [kg/m(2)] 50 or greater) on short-term clinical outcomes and report 1-year mortality. Fifty-seven patients were found to have a body mass index of 50 or greater among 14,449 patients who underwent cardiac surgery between July 2000 and June 2007. Multivariable logistic regression analyses were used to assess the independent influence of extreme obesity on the major outcomes. Of the 57 patients, the mean age was 58 +/- 11 years, mean body mass index was 55.1, and 63% of the patients were women. Forty patients underwent elective surgery. Forty-one patients had isolated coronary artery bypass graft surgery. The overall operative mortality was 9%; the mortality was 5% in isolated coronary artery bypass graft surgery and 5% in elective surgery. Fifteen patients had nonelective isolated coronary artery bypass graft surgery, and 2 patients had emergent active endocarditis surgery. Off-pump coronary artery bypass graft surgery was performed on 23 patients (23 of 41, 54%). After adjusting for known preoperative and operative risk factors through a multivariate logistic model, extreme obesity did not emerge as a significant risk factor for operative mortality (odds ratio, 1.75; p = 0.47) and other adverse outcomes (p > 0.05) after elective surgery; however, extreme obesity was marginally associated with increased mortality (odds ratio, 2.69; p = 0.05) and was a risk predictor for longer intensive care unit stays (odds ratio, 2.43; p = 0.01) in overall surgery. The 1-year survival rate was 82.5%. Extreme obesity is not a contraindication to elective cardiac surgery. Studies stratifying the risk factors of mortality for nonelective surgery in extremely obese patients may be warranted.
Article
It is well documented that malnourished and/or obese surgical patients have increased morbidity and mortality post-operatively. Only a few studies investigating the effect of nutritional status on mortality are available pertaining to the transplant population. Since limited data are available on the nutritional status and its effects on mortality in the lung transplant population, we sought to ascertain whether there is an association between mortality and preoperative nutritional status. We examined mortality during the first 3 months after transplantation. Patients were grouped by body mass index (BMI) categories as < 17 kg/m(2), 17 to < 20 kg/m(2), 20 to 25 kg/m(2) (reference group), > 25 to 27 kg/m(2), and > 27 kg/m(2). Additional risk factors retrieved from the pre-transplant records included age, gender, diagnosis, energy requirements, protein requirements, protein and caloric intake, and weight history. Logistic regression for univariate and multivariate analysis for mortality used recipient age, gender, disease category, pre-transplant cytomegalovirus (CMV) serology, transplant type (single or bilateral), and donor age, gender, and CMV serology. The likelihood estimates or odds ratios (ORs) of the risk of death within 90 days of lung transplantation for the BMI categories compared to the reference group were 3.7 for BMI < 17 kg/m(2) (p = 0.085), 1.6 for BMI < 17 to 20 kg/m(2) (p = 0.455), 3.5 for BMI > 25 to 27 kg/m(2) (p = 0.069), and 5.0 for BMI > 27 kg/m(2) (p = 0.003). In patients with a pre-transplant BMI < 17 kg/m(2) or > 25 kg/m(2) the risk of dying within 90 days post-transplant was increased. In patients with a pre-transplant BMI of > 27 kg/m(2) the risk was significantly higher in than the reference group.
Article
Extremes in body weight are a relative contraindication to cardiac transplantation. We retrospectively reviewed 474 consecutive adult patients (377 male, 97 female, mean age 50.3+/-12.2 years), who received 444 primary and 30 heart retransplants between January of 1992 and January of 1999. Of these, 68 cachectic (body mass index [BMI]<20 kg/m2), 113 overweight (BMI=>27-30 kg/m2), and 55 morbidly obese (BMI>30 kg/m2) patients were compared with 238 normal-weight recipients (BMI=20-27 kg/m2). We evaluated the influence of pretransplant BMI on morbidity and mortality after cardiac transplantation. Kaplan-Meier survival distribution and Cox proportional hazards model were used for statistical analyses. Morbidly obese as well as cachectic recipients demonstrated nearly twice the 5-year mortality of normal-weight or overweight recipients (53% vs. 27%, respectively, P=0.001). An increase in mortality was seen at 30 days for morbidly obese and cachectic recipients (12.7% and 17.7%, respectively) versus a 30-day mortality rate of 7.6% in normal-weight recipients. Morbidly obese recipients experienced a shorter time to high-grade acute rejection (P=0.004) as well as an increased annual high-grade rejection frequency when compared with normal-weight recipients (P=0.001). By multivariable analysis, the incidence of transplant-related coronary artery disease (TCAD) was not increased in morbidly obese patients but cachectic patients had a significantly lower incidence of TCAD (P=0.05). Cachectic patients receiving oversized donor hearts had a significantly higher postoperative mortality (P=0.02). The risks of cardiac transplantation are increased in both morbidly obese and cachectic patients compared with normal-weight recipients. However, the results of cardiac transplantation in overweight patients is comparable to that in normal-weight patients. Recipient size should be kept in mind while selecting patients and the use of oversized donors in cachectic recipients should be avoided.
Article
Studies assessing morbidity and mortality in obese patients undergoing orthotopic liver transplantation (OLT) have produced conflicting results, mainly because of the small sample size. The objective of our study was to determine graft and patient survival in obese adults receiving OLT in the U.S. between 1988 through 1996 using the United Network for Organ Sharing (UNOS) database. Among the 23,675 transplantations performed during the 9-year study period, 18,172 (75%) patients fulfilled the inclusion criteria. Of these, 8,382 (46%) were nonobese (body mass index [BMI] < 25 kg/m(2)), 5,913 (33%) were overweight (BMI, 25.1-30 kg/m(2)), 2,611 (14%) were obese (BMI, 30.1-35 kg/m(2)), 911 (5%) were severely obese (BMI, 35.1-40 kg/m(2)), and 355 (2%) were morbidly obese (BMI, 40.1-50 kg/m(2)). The outcome measures assessed were immediate (30-day), 1-, 2-, and 5-year patient survival. Obese groups had a higher proportion of women, a greater prevalence of cryptogenic cirrhosis (P <.05) and diabetes (P <.05), and a higher serum creatinine. Primary graft nonfunction, and immediate, 1-year, and 2-year mortality were significantly higher in the morbidly obese group (P <.05). Five-year mortality was significantly higher both in the severely and morbidly obese subjects (P <.05), mostly as a result of adverse cardiovascular events. Kaplan-Meier survival was significantly lower in morbidly obese patients, and morbid obesity was an independent predictor of mortality. Obesity is associated with a significant increase in long-term mortality, mostly as a result of cardiovascular events. Weight loss should be recommended for all patients awaiting a liver transplantation, especially if their BMI is more than 35 kg/m(2).
Article
Renal transplant recipients with elevated body mass index (BMI) have been shown to have inferior patient survival as compared to patients with lower BMI. However, previous studies could not establish a link between increased BMI and decreased death censored graft survival. Obesity in nontransplant patients has been associated with hypertension, hyperlipidemia, type II diabetes, proteinuria and glomerulopathy. Given this evidence it is possible that renal transplant recipients with an elevated BMI may have worse long term graft survival. To investigate this hypothesis we retrospectively analyzed 51,927 primary, adult renal transplants registered in the USRDS. BMI at date of transplant was calculated for all patients using BMI=body weight (in kg)=.stature (height, in meters) squared. BMI values were further categorized into 11 categories: below 18, from 18 to 36 at 2 unit increments, and above 36 kg/m2. Primary study end points were graft and patient survival. Secondary study end points were death censored graft survival, chronic allograft failure, delayed graft function, and acute rejection (AR). Cox proportional hazard and logistic regression models investigated the link between categorized BMI and the study end points correcting for potential confounding variables. BMI showed a very strong association with outcomes after renal transplantation. The extremes of very high and very low BMI were associated with significantly worse patient and graft survival. The same was true for death censored graft survival and chronic allograft failure. Elevated BMI was also associated with an increased risk for delayed graft function while lower BMI was significantly protective. Acute rejection did not show any significant association with BMI. BMI has a very strong association with outcomes after renal transplantation independent of most of the known risk factors for patient and graft survival. The extremes of very high and very low BMI before renal transplantation are important risk factors for patient and graft survival. It is important to note that elevated BMI was significantly associated with worse graft survival independent of patient survival. Whether prospective weight adjustment before renal transplantation can favorably affect posttransplant risk needs to be assessed by further studies.