Guidelines for the Selection of Lung Transplant Candidates Am. J. Respir.
Crit. Care Med., Volume 158, Number 1, July 1998, 335-339
THIS JOINT STATEMENT
OF THE AMERICAN SOCIETY FOR TRANSPLANT PHYSICIANS (ASTP) AMERICAN THORACIC
SOCIETY (ATS)/EUROPEAN RESPIRATORY SOCIETY (ERS)/INTERNATIONAL SOCIETY
FOR HEART AND LUNG TRANSPLANTATION (ISHLT) WAS APPROVED BY THE ATS BOARD
OF DIRECTORS FEBRUARY, 1998
More than 6,400 lung
transplants have been performed since the first successful operations in
(1). Lung transplant
programs now exist in many countries. Internationally, the number of donor
organs available is far fewer than the number of patients with end-stage
lung disease. Because of this, many candidates die on the waiting
list, and the average wait to receive a donor organ may approach 2 yr
(2). Overall survivals
are between 60 and 65% at 2 yr and approximately 40% at 5 yr (1). Considering
the resource limitations and the importance of assuring optimum outcomes,
we believe that international guidelines for selection of appropriate candidates
for lung transplant will ensure a fair distribution of donor organs. Transplant
physicians and surgeons representing the International Society of Heart
and Lung Transplantation, the American Society of Transplant Physicians,
the American Thoracic Society, the European Respiratory Society, and the
Thoracic Society of Australia and New Zealand have agreed on the information
in the following document as acceptable guidelines for candidates for lung
transplantation. Our aim is that this document will assist physicians throughout
the world who are treating patients with pulmonary diseases to identify
potential candidates for lung transplantation.
This document is
divided into two sections. The first describes general health guidelines
that all candidates for lung transplantation should meet; the second describes
disease-specific exercise or lung function criteria that are generally
felt to identify patients whose poor prognosis from their underlying diseases
justify transplantation. Candidates for either live donor organs or cadaver
donor organs should meet the same selection criteria. In all cases it must
be remembered that these guidelines are a general statement and that individual
patients might have specific circumstances that do not meet all guidelines
yet would be acceptable transplant candidates.
remains a developing field within pulmonary medicine and thoracic surgery.
It is anticipated that with increasing experience and knowledge the state
of the art will change and these guidelines will require review and modification.
FOR CANDIDATE SELECTION FOR LUNG TRANSPLANTATION
patients for lung transplantation should ensure that the patient has received
or is receiving maximum, optimal medical therapy for his disease but nevertheless
has declining function. In general, candidates should have chronic disease
for which no further medical or surgical therapy is available and survival
is limited; lung transplantation is rarely an option for acutely, critically
ill patients. Comorbid medical conditions should also be optimally treated
in transplant candidates, and routine preventive medicine measures (such
as mammograms, Pap smears, and colon cancer screening) should be completed
Older patients have
a significantly worse survival rate than younger patients (1). The following
guidelines are suggested.
~ 55 years
Single lung transplants
~ 65 years
Bilateral lung transplants
~ 60 years
CONDITIONS THAT IMPACT ON ELIGIBILITY FOR LUNG TRANSPLANTATION.
The following are
a list of general medical conditions that are felt to impact on the long-term
outcome of lung transplant recipients. Medical or psychosocial treatment
to address these issues should be instituted when appropriate in patients
who do not currently, but may ultimately, meet the criteria for lung transplantation.
However, in most cases, referral should not be delayed while patients are
undergoing corrective treatment. Other medical conditions which,
when they have not resulted in organ damage, are generally acceptable in
candidates for lung transplantatione.g., systemic hypertension, diabetes
mellitus, peptic ulcer disease, should also be optimally treated and well
controlled. In the presence of any comorbid medical condition with the
potential for end organ damage, a careful search should be made for evidence
of organ dysfunction.
is a relative contraindication to transplantation and the potential risk
to acceptable long term outcome should be assessed on a case by case basis
(3). Both symptomatic and asymptomatic significant disease requires treatment
that should be initiated prior to transplant. Patients should be fully
investigated and followed by appropriate objective measures, i.e., bone
densitometry. Severe musculoskeletal disease affecting the thorax,
e.g., kyphoscoliosis, is a relative contraindication, and progressive neuromuscular
disease is an absolute contraindication to lung transplantation.
Current use of corticosteroids is not a contraindication to transplantation;
however, all attempts to discontinue these drugs or at least reduce the
dose to 20 mg/d prednisolone or prednisone should be made (4).
are an important predictor of surgical outcome (5, 6). Patients with an
ideal body weight (IBW)< 70% or > 130% percent require either weight
gain or weight loss to become eligible for transplant. Candidates for lung
transplantation must have been free of substance addiction, e.g., alcohol,
tobacco, narcotics, for at least 6 mo. Appropriate preoperative biochemical
monitoring is recommended in at-risk patients. Psychosocial problems
that are unable to be resolved and that have a high likelihood of impactingnegatively
on the patient's outcome, e.g., poorly controlled major psychoaffective
disorder, inability to comply with complex medication regimen, are a relative
contraindication. A documented history of noncompliance with medical care
or treatment plans even in the absence of documented psychiatric problem
is a relative contraindication. Requirement for invasive ventilation is
a relative contraindication to transplant. Patients receiving noninvasive
ventilatory support who meet all other criteria are eligible for lung transplantation.
Colonization with fungi or atypical mycobacteria is not an absolute contraindication
to transplantation. Cases should be considered on an individual basis,
and special care should be taken when a unilateral transplant is considered.
When possible, attempts preoperatively to eradicate colonization with antibiotic
therapy are appropriate. Adequately treated M. tuberculosis is not
a contraindication to lung transplantation.
Dysfunction of major
organs other than the lung is a contraindication, particularly renal dysfunctioncreatinine
clearance of < 50 mg/ml/minbecause of the impact of immunosuppressive
drugs on renal function (7). Patients with significant untreatable coronary
artery disease or left ventricular dysfunction warrant consideration for
heart-lung transplant. Infection with HIV. Active malignancy within
the past two years with the exception of basal cell and squamous cell carcinoma
of skin. In addition, recent data on recurrence of tumors posttransplant
suggest that a waiting period of at least 5 yr is prudent for extracapsular
renal cell tumors, breast cancer stage 2 or higher, colon cancer staged
higher than Dukes A, and melanoma, level III or higher (8). Hepatitis
B antigen positivity. Hepatitis C with biopsy-proven histologic evidence
of liver disease.
Lung transplant is
not contraindicated per se in patients with systemic disease, e.g., collagen
mellitus (9). Each potential candidate should be considered on an individual
basis with particular attention paid to the presence of any target organ
damage outside the lung that might affect long-term outcome. This would
constitute a relative or absolute contraindication.
Diagnostic and Prognostic
Investigations before Referral
The following list
of studies are considered useful by most transplant centers in assessing
potential candidates. Queries regarding specific center requirements should
be directed to that center and, when possible, efforts should be made to
avoid duplicate studies.
*Full lung function tests
*Exercise performance measured by a standardized test, e.g., six-minute
*High resolution computed tomography (HRCT) of the thorax in patients with
parenchymal disease, pleural disease, or previous thoracic surgical
*Stress echocardiograme.g., dobutamine, dobutamine PET, sestamibi, etc.and/or
coronary angiograms in patients at high risk for coronary artery disease
* 24-hour creatinine clearance
* Liver function studies
Chronic Obstructive Lung Disease
This disease category
encompasses a number of diagnoses of which the most common are emphysema,
and bronchiolitis obliterans. Every effort should be made to exclude asthma
and to maximally treat any reversible component of the airways disease
prior to referral for transplant workup. Pulmonary rehabilitation and long-term
oxygen therapy should also be included in medical management prior to referral
to a transplant center. Other treatment options such as volume reduction
surgery for emphysema patients may also be considered in appropriate candidates
(10). It is inherently difficult to accurately predict survival in many
patients with advanced obstructive disease (13). In terms of transplant
outcome, therefore, some of these patients may experience improved functional
capacity but not necessarily improved survival.
are considered potentially to be in the transplant window if they meet
the following criteria (16, 17):
FEV1 < 25% of
predicted (without reversibility) and/or PaCO2 55 mm Hg (7.3 kPa)
and/or elevated pulmonary artery pressures with progressive deterioration,
e.g., cor pulmonale. Preference should be given to those patients with
elevated PaCO2 with progressive deterioration who require long-term oxygen
therapy, as they have the poorest prognosis (18).
2. Cystic Fibrosis
and other Bronchiectatic Diseases
Patients with cystic
fibrosis have special problems related to the microbiology of their pulmonary
secretions, particularly with respect to resistant organisms (19, 20).
Controversy exists as to the outcome of patients colonized with multiply
resistant P. aeruginosa and B. cepacia (biologically, B. cepacia is inherently
multiply resistant). The following definitions may be used to categorize
the resistance of pseudomonal and related organisms (21):
A multiple resistant
organism is resistant to all agents in two of the following classes of
A pan-resistant organism
is resistant in vitro to all groups of antibiotics.
A substantial number
of patients will have organisms that are pan resistant in vitro. However,
in vitroresistance does not equate with in vivo resistance. Different combinations
of antibiotics may function synergistically in vivo. Thus multiple resistance
is not a contraindication to transplantation in this group of patients.
Colonization with pan-resistant organisms should be considered a relative
contraindication to transplantation because of concern about long-term
outcomes in these patients. Occasionally, specialized testing of different
combinations of antibiotics against organisms considered to be pan-resistant
to the usual antibiotic regimens may demonstrate sensitivity to new drug
combinations (synergy testing). Patients with presumed pan-resistant organisms
should be referred to a transplant center capable of this type of antibiotic
sensitivity testing, and each patient should be assessed on an individual
basis. Listing of such patients should be determined based on individual
of the sputum of listed patients should be done on a periodic basis, e.g.,
every 3 mo, or if intercurrent antibiotic treatment has been necessary.
The following criteria identify patients potentially within the transplant
FEV1 30% predicted
or rapid progressive respiratory deterioration with FEV1 > 30% predicted,
e.g., increasing numbers of hospitalizations, rapid fall in FEV1, massive
hemoptysis and increasing cachexia despite optimal medical management.
Resting arterial blood gases obtained while patient is breathing room airPaCO2
> 6.7 kPa (50 mm Hg); PaO2 < 7.3 kPa (55 mm Hg)are useful criteria and
are associated with a prognosis of < 50% survival in 2 yr; however,
patients should be considered candidates for transplant if they meet FEV1
criteria even though they may not yet be markedly hypercapnic or hypoxemic
(22). Young female cystic fibrosis patients who deteriorate rapidly have
a particularly poor prognosis (23). These patients should be evaluated
on an individual basis regardless of physiologic criteria.
Patients may present
for transplant consideration with bronchiectasis from other causesimmunodeficiency
syndromes, immotile or dysfunctional cilia syndromes, post-infection, etc.
Few data are available regarding projected survivals in such patients with
advanced disease, and that makes it more difficult to formulate guidelines
for selection. In general, the lung transplant community has followed the
guidelines listed above for cystic fibrosis patients.
Pulmonary Fibrosis (Cryptogenic Fibrosing Alveolitis)
fibrosis (IPF) refers to patients without evidence of other systemic disease
who present with diffuse fibrotic changes in the lung. The rapid progression
of this disease and the high mortality mandates early referral (24). It
is recognized that this is a disease that is more common among older people,
and therefore coexistent pulmonary and nonpulmonary morbidities that may
contraindicate transplant are common. Pulmonary conditions for which the
patient should be evaluated prior to referral are bronchogenic carcinoma,
pulmonary tuberculosis, and bronchiectatic areas colonized with pathogenic
organisms. A CT scan with high resolution images is useful in assessing
these issues as well as highlighting atypical features of a patient's disease
that may suggest an alternative diagnosis. Other frequent medical problems
mandating careful evaluation are steroid-related morbidities and symptoms
of coronary artery disease. Medical therapy, and especially oxygen therapy,
should be optimized and frequently reassessed in these patients. Testing
should be done both at rest and during exercise. Optimization of therapy
may include the withdrawal of steroids or other cytotoxic agents where
no meaningful benefit has been achieved.
Patients who meet
the following criteria are considered to be potentially within the transplant
rest or exercise oxygen desaturation), progressive disease with failure
to improve or maintain lung function while being treated with steroids
or other immunosuppressive drug therapy. Clinical assessment at frequent
intervals, e.g., every 3 mo, is extremely useful in evaluating the progression
of disease or failure to improve on drug therapy. If (when) pulmonary
function is (becomes) abnormal, even though the patient may be minimally
symptomatic, serious consideration should be given to referral to a transplant
center for initial evaluation. Patients are often symptomatic and have
advanced disease when the vital capacity falls below 60 to 70% predicted
and/ or the diffusing capacity (corrected for alveolar volume) falls below
50 to 60% predicted.
with Pulmonary Fibrosis
is a common lung pathology in a number of systemic diseases, e.g., scleroderma,
rheumatoid arthritis, sarcoidosis, post-chemotherapy. In patients with
these diagnoses, the manifestations of the underlying process are highly
variable and each patient should be considered on an individual basis.
In general, evidence of quiescent systemic disease is required. It is necessary
for all patients to meet general selection criteria and to have failed
optimum medical therapy to be considered for lung transplantation. The
criteria for timing of selection for transplant listed above should be
4. Pulmonary Hypertension
without Congenital Heart Disease
hypertension occurs as a primary process or as a secondary manifestation
of another disease. Typical causes of secondary pulmonary hypertension
include thromboembolic disease, venoocclusive disease, capillary hemangiomatosis,
medication-related, and collagen vascular disease. Patients with these
diagnoses generally have a poor prognosis (28).
in long-term vasodilator therapy have recently shown encouraging results
in patients with primary pulmonary hypertension (29). Less information
is available in patients with pulmonary hypertension as a secondary manifestation
of other disease; however, studies in selected patients are ongoing. In
some cases surgical therapy either a trial septostomy or thromboendarterectomy
depending on the underlying primary diagnosishas been reported to improve
symptoms and possibly survival (30, 31).
for lung transplant with a diagnoses of primary pulmonary hypertension
evaluated by a center
with experience in vasodilator therapy, and all patients should be evaluated
and other medical or surgical interventions prior to transplant consideration.
The following criteria should be met to consider a patient within the transplant
disease which, despite optimal medical and/or surgical treatment, leaves
the patient in NYHA III or NYHA IV. Where available prostacyclin should
be considered the gold standard for medical vasodilator therapy if there
is no objective indication that calcium channel blockers may be useful.
Useful hemodynamic parameters in assessing the failure of optimal pre-transplant
therapy include a cardiac index of less than 2 L/min/m2, a right atrial
pressure of more than 15 mm Hg, and a mean pulmonary artery pressure greater
than 55 mm Hg (28).
5. Pulmonary Hypertension
Secondary to Congenital Heart Disease (Eisenmenger's Syndrome)
in patients with congenital heart disease behaves differently prognostically
than in patients with other types of pulmonary hypertension. Hemodynamically,
similar pulmonary artery pressures are associated with better cardiac function
and lower right atrial pressures and a somewhat better prognosis (32).
Predictors of survival are less reliable. The role of vasodilator therapy
in pre-transplant management of these patients is not yet clear.
symptoms with function at NYHA III or NYHA IV level despite optimal medical
6. Combined Pulmonary
and Other Organ Failure
with failure of more than one organ have occasionally been considered candidates
for multiorgan transplantation. Advanced liver disease, for example,
can be associated with pulmonary
Selected patients with liver and lung disease may be candidates for liver-lung
transplants (34). Similarly, patients with heart and lung disease or kidney
and lung disease or some other organ failure combination might occasionally
be candidates for a multiorgan transplant. In each case the candidate should
meet all the criteria for selection for the individual transplant. Furthermore,
since experience in this area is limited and outcomes not well studied,
only well established centers with transplant programs in each of the organ
systems involved should consider such procedures.
in children is evolving (35). Diseases that are potentially amenable to
lung transplantation include primary pulmonary hypertension, pulmonary
hypertension associated with structural heart disease, pulmonary vein stenosis,
pulmonary hypertension associated with parenchymal lung disease, and congenital
abnormalities of lung development or of lung adaptation to extrauterine
life. As in adults, maximal medical therapy including vasodilators and
supplemental oxygen should be instituted before children are considered
for transplantation. Since the diagnoses are varied and the disease spectra
diverse, prognostic indicators have been difficult to develop; thus empirical
criteria are the primary means of selecting candidates.
Disease no longer responding to maximum medical and surgical treatment
Moderately severe or severe functional impairment (NYHA Class III or IV)
Right ventricular failure, severe cyanosis, and low cardiac output
In order to arrive
at appropriate decisions it is necessary to follow up these patients with
great care in centers that specialize in pediatric work. Careful assessment
of all these patients is vital to exclude other correctable cardiac defects
contributing to pulmonary hypertension.
with parenchymal lung disease or abnormalities of development or adaptation
need to be individually assessed as only single cases of patients receiving
transplants have been described. These diseases include: congenital diaphragmatic
hernia, congenital surfactant protein B deficiency, and congenital cystic
emphysematous lung disease.
Other diseases presenting
in advanced stages in children include among others cystic fibrosis, bronchiolitis
obliterans, pulmonary fibrosis and bronchopulmonary dysplasia. It is often
difficult, because of the limited available historical data, to make accurate
predictions regarding survival. As in the case of the cardiopulmonarydiseases,
patients may be considered candidates for transplant when progressive disability
occurs (NYHA III or IV) despite optimal medical therapy. In the case of
cystic fibrosis patients, guidelines for adult patients can be generally
adapted to the pediatric population.
Richard G. Barbers, Robyn Barst, Maher A. Baz, Willem
de Boer, Paul A. Corris,
R. Duane Davis, Jim J. Eagan, Thomas M. Egan, Edward
R. Garrity Jr.,
Leo C. Ginns,
Sergio Harari, Sheila Haworth, Marshall I. Hertz, Robert
J. Keenan, Cesar Keller,
Thomas J. Kirby, Timothy J. Locke, George B. Mallory,
I. L. Paradis,
G. A. Patterson, Stuart Rich, Lewis J. Rubin, Mark Schluchter,
Larry L. Schulman,
Victor F. Tapson, E. P. Trulock, Carol Vreim, Martin
This statement was
developed by an international group of lung transplant physicians and surgeons.
The final document
was prepared by a coordinating committee whose members are: Janet R. Maurer
Adaani E. Frost (ASTP), Allan R. Glanville (TSANZ),
Marc Estenne (ERS),
and Timothy Higenbottam (ISHLT).
This Statement is
being copublished with the European Respiratory Journal, Heart and Lung
Transplantation, and Transplantation, and copyrighted with the ASTP and
Supported by educational grants from Glaxo and Novartis through the International
Society for Heart and Lung Transplantation, the American Society of Transplant
Physicians and the American Thoracic Society.
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