Two decades of pediatric lung transplant in the United States: have we improved?
ABSTRACT Since 1988, approximately 1100 pediatric lung transplants have been performed worldwide with consistent improvement in survival. Similarly, survival for pediatric heart transplant has increased over the years; however, in this cohort improvement in survival is exclusively a result of increased early (1-year) survival. To observe if this same phenomenon exists in pediatric lung transplants, the United Network for Organ Sharing database was analyzed to evaluate and characterize how pediatric lung transplant survival has changed in the past 2 decades.
The United Network for Organ Sharing database was queried for patients aged 18 years or less who underwent lung transplantation from May 1988 to May 2008. Analysis included 959 pediatric lung transplants.
Age groups were infants (≤1 years) (n = 106 [11%]), children (2-12 years) (n = 299 [31%]), and adolescents (≥13 years) (n = 554 [58%]). A total of 546 (57%) were girls. Kaplan-Meier survival was significantly better in the late era (2002-2008) than in all other eras (1988-1994 and 1995-2001) (P < .05). The half-life for graft has increased significantly over the eras (early, 2.2 years; mid, 3.3 years; and late, 3.8 years). Conditional 1-year survival (ie, mid to late survival) was not significantly different (P = .3) among the eras. Gender, age, diagnosis, prolonged ischemic time, and cytomegalovirus mismatch did not significantly affect overall patient or graft survival. Chronic preoperative steroid dependence (P = .02), preoperative ventilatory dependence (P < .001), and retransplantation (P = .02) were associated with decreased survival.
Survival in pediatric lung transplant has increased significantly over the years, but this improvement primarily reflects improvement in early survival. Survival in pediatric lung transplant after the first posttransplant year has not changed in more than 2 decades.
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ABSTRACT: BACKGROUND: There have been >1,600 pediatric lung transplantations (LTx) performed worldwide with a trend toward improved outcomes over the last 25 years. The majority of these LTxs have been in older children and adolescents. Less than 4 infant (defined as≤12 months of age) LTxs per year have been performed over the past 20 years, mostly in the USA. However, infant LTx outcomes have not been well documented in a multi-institutional longitudinal fashion. METHODS: The United Network of Organ Sharing database was queried from October 1987 to July 2011. Of the 1,003 pediatric LTxs reported, 84 (8%) were infants. All combined transplantations were excluded. RESULTS: Eighty-one infants received 84 LTxs, of which 95% had a bilateral LTx. Median age and weight at LTx was 4 months (range 0 to 11 months) and 5.3 kg (2.7 to 11.8 kg), respectively. Median ischemic time was 5.2 hours (2.0 to 10.8 hours). Overall Kaplan-Meier graft survival was similar for infants compared with other pediatric age group (OPA: >1 to 18 years) LTx recipients (half-life 4.0 years vs 3.4 years, p = 0.7). Conditional 1-year graft survival for infants was significantly higher than OPA (half-life 7.4 years vs 5.0 years, p = 0.024). Early (1987 to 2000, n = 46) and late (2001 to 2011, n = 38) era graft survival was not significantly different. Graft survival in pre-LTx ventilated infants was significantly better than pre-LTx ventilated OPA (half-life 6.1 years vs 0.9 year, p = 0.004) and was not statistically different from pre-LTx infants not on ventilatory support (half-life 6.1 years vs 2.2 years, p = 0.152). Cox regression of 5 variables (weight, donor arterial PO(2), pre-Tx ventilator, organ ischemic time, center experience) showed that survival was associated with increased center experience (p = 0.03). CONCLUSION: Infants undergoing LTx have outcomes similar to those of all other pediatric LTx patients.The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 11/2012; · 5.61 Impact Factor
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ABSTRACT: Lung transplantation (LTx) is a treatment option for infants and children with untreatable and otherwise fatal pulmonary diseases. To date, over 1,800 lung transplants have been performed, most frequently in children over the age of five years. The most common indications for transplantation in children overall are cystic fibrosis (CF) and idiopathic pulmonary hypertension (PH). The surfactant protein deficiencies, other interstitial lung diseases (ILDs), and congenital heart disease are important indications among young children and infants. Re-transplantation is an option for selected recipients with chronic allograft rejection. Overall survival following pediatric LTx is similar to that encountered in adult patients, with recent registry data indicating a median survival of 4.9 years. Other outcomes such as the incidence of bronchiolitis obliterans (BO) and the presence of key post-transplant co-morbid conditions are also similar to the experience in adult lung transplant recipients.Journal of thoracic disease. 08/2014; 6(8):1024-31.
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ABSTRACT: Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%.Archivos de Bronconeumología 11/2013; · 2.17 Impact Factor
Two decades of pediatric lung transplant in the United States: Have
Farhan Zafar, MD, Jeffrey S. Heinle, MD, Marc G. Schecter, MD, Joseph W. Rossano, MD,
George B. Mallory, Jr, MD, Okan Elidemir, MD, and David L. S. Morales, MD
Objective: Since 1988, approximately 1100 pediatric lung transplants have been performed worldwide with
consistent improvement in survival. Similarly, survival for pediatric heart transplant has increased over the
To observe if this same phenomenon exists in pediatric lung transplants, the United Network for Organ Sharing
Methods: The United Network for Organ Sharing database was queried for patients aged 18 years or less who
underwent lung transplantation from May 1988 to May 2008. Analysis included 959 pediatric lung transplants.
Results: Age groups were infants (?1 years) (n ¼ 106 [11%]), children (2–12 years) (n ¼ 299 [31%]), and
adolescents (?13 years) (n ¼ 554 [58%]). A total of 546 (57%) were girls. Kaplan–Meier survival was signif-
icantly better in the late era (2002–2008) than in all other eras (1988–1994 and 1995–2001) (P<.05). The
half-life for graft has increased significantly over the eras (early, 2.2 years; mid, 3.3 years; and late, 3.8 years).
der, age, diagnosis, prolonged ischemic time, and cytomegalovirus mismatch did not significantly affect overall
patient or graft survival. Chronic preoperative steroid dependence (P ¼ .02), preoperative ventilatory depen-
dence (P<.001), and retransplantation (P ¼ .02) were associated with decreased survival.
Conclusions: Survival in pediatric lung transplant has increased significantly over the years, but this improve-
ment primarily reflects improvement in early survival. Survival in pediatric lung transplant after the first post-
transplant year has not changed in more than 2 decades. (J Thorac Cardiovasc Surg 2011;141:828-32)
Supplemental material is available online.
The first human lung transplant was performed by Dr James
Hardy at the University of Mississippi in 1963 for an iso-
lated cancer of the lung.1Between 1963 and 1980, approx-
imately 44 transplants were performed at medical centers
around the world with no real success. Most of these trans-
plants were performed on debilitated patients as ‘‘rescue’’
attempts after they becameventilator-dependent. Only 2 re-
cipients lived more than 1 month. The advent of new tech-
niques and immunosuppressive therapies made possible the
first successful single lung transplant, which was performed
by Dr Joel D. Cooper in 1983. This achievement was
followed by the first successful double lung transplant in
The first pediatric lung transplant (PLT) was performed at
the University of Toronto in 1987 in a 15-year-old boy with
familial pulmonary fibrosis.3However, lung transplantation
in children has not been as widely embraced as in the adult
In recent years, approximately 70 to 75 PLTs have been
performed yearly in 28 centers across the world, with only
2 centers performing more than 10 transplants each year.4
Since the 1980s, survival in pediatric heart transplanta-
tion has improved significantly.5However, the present
authors previously demonstrated that all improvements in
survival were in reality only an increase in early survival.6
After the first posttransplant year, survival in pediatric heart
transplantation has not changed in more than 2 decades. To
observe whether the same phenomenon exists in PLT, an
analysis of all the PLTs recorded in the Organ Procurement
and Transplantation Network (OPTN) Thoracic Registry
MATERIALS AND METHODS
A retrospective analysis of OPTN data as of May 2008 was performed.
The OPTN is the unified transplant network established by the United
From the Michael E. DeBakey Department of Surgery, Division of Congenital Heart
Surgery, Baylor College of Medicine, Houston, Tex.
Disclosures: Authors have nothing to disclose with regard to commercial support.
Presented at the 29th Annual Meeting of The International Society for Heart & Lung
Transplantation, April 22–25, 2009, Paris, France.
Received for publication Feb 9, 2010; revisions received April 19, 2010; accepted for
publication June 1, 2010; available ahead of print Jan 21, 2011.
Address for reprints: Farhan Zafar, MD, Congenital Heart Surgery, Texas Children’s
Hospital, 6621 Fannin Street MC-WT 19345H, Houston, TX 77030 (E-mail:
Copyright ? 2011 by The American Association for Thoracic Surgery
828The Journal of Thoracic and Cardiovascular SurgerycMarch 2011
Cardiothoracic TransplantationZafar et al
States Congress under the National Organ Transplant Act of 1984. The
United Network for Organ Sharing is a private, nonprofit organization
that administers the OPTN under federal contract.
Analysis was limited to patients in the United Network for Organ Shar-
ing/OPTN Thoracic database who were aged less than 18 years and who
underwent lung transplantation between May of 1988 and May of 2008.
Of a total of 17,207 lung transplants, 959 (5.5%) were PLTs. Patients
were divided according to the year of transplant into 3 groups: early
(1988–1994), mid (1995–2001), and late (2002–2008) eras.
There were 490 possible data points; many of these fields were infre-
quentlypopulated.Therefore,the analysiswas limitedonly to thevariables
that were at least 80% populated, with the exception of cytomegalovirus
mismatch for which only 40% had the information available. Twenty-
five variables met this criterion; on the average, these variables were
95% populated. For baseline characteristics, continuous variables were
compared using t test and analysis of variance, with the Tukey method
for controlling for multiple comparisons. Categoric variables were com-
pared using the chi-square test. Survival curves were estimated using the
Kaplan–Meier method, and equality of survival curves was tested using
a log-rank test. Multivariate analyses were performed using Cox propor-
tional hazards regression models.
The mean age and weight of the recipients were 12 ? 5.6
years and 33.6 ? 16.3 kg, respectively, and the mean age
and weight of the donors were 17.6 ? 15 years and 41.6
? 24 kg, respectively. A total of 106 (11%) of the total co-
hort were infants (aged ?1 year), 299 (31%) were aged 2 to
12 years, and 554 (58%) were adolescents (aged ?13
years). A total of 546 (57%) were girls. Ethnic composition
of the cohort was Caucasian (83%, 795), Hispanic (8%,
80), African American (5%, 50), and others (4%, 34).
Some 51% (490) of the cohort had a gender-matching
transplant. Gender-mismatch transplants consisted of
female recipients who had a male donor (29%, 273) and
male recipients who had a female donor (20%, 196).
Some 48% (264/554) of the adolescents had an adult donor.
A median of 51 (1–73) transplants were performed each
year over the 20 years, and a median of 60 (57–62) trans-
plants were performed over the last 5 years.
(53%), primary pulmonary hypertension in 104 patients
(11%), transplant-related bronchiolitis obliterans (BO) in
50 patients (5%), primary BO in 34 patients (3.5%), inter-
218 patients (28%). Incidences of different diagnosis are
outlined in Table E1 (available online). Some 31% of pa-
tients (298) were receiving steroids, and 16% of patients
(155) were ventilator dependant at the time of transplant;
7% of patients (64) had a pan-resistant bacterial infection
before transplant, and in the last 2 years this incidence
had significantly increased (P <.001) to 22% (17/76);
13% of patients (125) had a previous thoracic operation
that was nontransplant related. Median overall waiting
time was 5 (0–96) months. Infants (1 [0–7] months) had
a significantly shorter (P <.001) waiting time than those
aged 2 to 12 years (4 [0–84] months) and adolescents
(8 [0–96] months).
Transplantation and Posttransplant Characteristics
Bilateral lung transplantation was performed in 94%
(899) of the cohort, and retransplantation was performed
in 8% (81) of the cohort. A living donor transplant was
performed in 11% (106) of PLTs, with only 2 (1.5%)
performed in last 3 years. Mean organ ischemic time was
5 ? 2 hours.
FIGURE 1. Kaplan–Meier curves: patient survival in different eras (A) and graft survival in different eras (B).
Abbreviations and Acronyms
¼ bronchiolitis obliterans
OPTN ¼ Organ Procurement and Transplantation
¼ pediatric lung transplant
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The Journal of Thoracic and Cardiovascular SurgerycVolume 141, Number 3 829
Incidences of posttransplant morbidities were as follows:
3% (27), and airway dehiscence 0.8% (8). Median length
of hospital stay was 19 days (1–326 days), and this has
not changed significantly (P>.05) among the eras.
Patient and Graft Survival
nificantly better in the late era compared with the other 2
eras (P <.05) (Figure 1). Kaplan–Meier survival condi-
tional on 1 year was not significantly different (P >.2)
among the eras (Figure 2) for patient or graft. Some 51%
(490) of the cohort were reported as dead. The cause of
death was graft failure in 35% (169) and infection in
23% (114). Causes of death are outlined in Table E2 (avail-
able online). Overall graft survival is shown in Figure 3.
Table 1 shows overall graft survival and comparison of sur-
vival for different eras at 1, 3, and 5 years. Patient survival
for children aged 2 to 12 years was better than for children
aged 13 to 18 years; however, graft survival was not signif-
icantly different among age groups (Figure 4).
Multivariate Analyses of Patient Survival
Gender, agegroups, diagnosis, and cytomegalovirus mis-
vival. Chronic steroid dependence (P ¼ .02), pretransplant
ventilator dependence (P < .001), and retransplantation
(P ¼ .02) were associated with significantly increased over-
all mortality (Table 2). The risk factors for early mortality
(?1 year) were the same as for overall mortality. However,
there were no risk factors found to be associated with late
mortality (>1 year).
Lung transplantation has movedinto a new era of success
with 3 major changes: (1) the advent of currently used sur-
gical techniques by Patterson and associates,7addressing
the issues of airway anastomosis and prolonged ischemia;
(2) the introduction of cyclosporine in 1983, which resulted
in dramatically improved survival; and (3) the adoption of
close collaboration between the medical and surgical teams
in the care of these patients that has continued to improve
The results of the current analysis substantiate the infer-
ence made by the 2008 International Society for Heart &
Lung Transplantation registry that survival in the late era
of PLT is significantly greater than in the earlier eras.4This
difference is clearly driven by an improvement in 1-year
(early) survival as highlighted by the conditional 1-year sur-
vival curves that are virtually identical for the different eras
(Figure 2). These survival curves censor 1-year mortality so
FIGURE 2. Kaplan–Meier curves conditional on 1-year survival: patient survival in different eras (A) and Graft survival in different eras (B).
FIGURE 3. Overall graft survival.
TABLE 1. Graft survival
Overall Early era Mid eraLate era
3.8 y2.2 y
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830The Journal of Thoracic and Cardiovascular SurgerycMarch 2011
that a direct comparison of midterm and late survival is pos-
sible. We reported the same phenomenon in pediatric heart
transplantation.6This improvement in early PLT survival is
likely due to advances in surgical, anesthetic, and critical
care management, and improvements in lung preservation,
infection control, and strategies to combat early rejection.
Also, the refinement in candidate selection over the years
as the field has matured likely has helped to improve early
now perform transplantation in patients with cystic fibrosis
who are on ventilators. However, no significant advances
have been made to treat chronic rejection in pediatric lung
or heart transplantation since the introduction of cyclospor-
ine in 1983. BO remains the most common cause of PLT
graft failure beyond the first year of transplant.4Enormous
trends in immunosuppression (ie, increased use of
mycophenolate, sirolimus, and tacrolimus), the mortality
rate for PLT after the first posttransplant year has not
changed in more than 20 years.4
Pretransplant chronic steroid use, ventilator dependence,
and retransplantation were found to be independent risk fac-
tors for poor graft survival, as has been reported by other
groups.11,12Although mechanical ventilation is a significant
risk factor for morbidity and mortality in adults and older
children, the impact on infants is less clear.13,14Nonetheless,
in this analysis pretransplant mechanical ventilatory support
is an independent risk factor for graft failure at all ages. In
this cohort, mid to late survival (>1 year) seemed to be
unaffected by any of the variables analyzed.
Although there is conflicting evidence regarding the
impact of pretransplant pan-resistant bacterial infection on
the outcome of lung transplant recipients,15-18the present
study did not show it to be a risk factor for mortality.
However, a significant increase over the past few years in
the incidence of pan-resistant bacterial infection is noted at
ter lung transplantation compared with those infecting the
complex infections, has been associated with poor outcomes
and early mortality posttransplant.19,20
cenocepacia (previously known as Genomovar 3), a virulent
speciesof Burkholderia, is
contraindication to lung transplantation in most centers.
Although the use of multiple combinations of bactericidal
antibiotics for eradication of Burkholderia species has been
proposed, empiric evidence of successful outcome after
lung transplantation, especially in regard to B. cenocepacia,
is still lacking.
Early posttransplant survival has significantly improved
to such an extent that it has prolonged the overall survival
after PLT dramatically. Unfortunately, chronic rejection
continues to dominate late graft survival with little
FIGURE 4. Kaplan–Meier curves: patient survival for different age groups (A) and graft survival for different age groups (B).
TABLE 2. Risk factors analyzed for graft loss
Multivariate survival analysis
Hazard ratio Lower Upper
Diagnosis (cystic fibrosis)
Pretransplant steroid dependence
Ischemic time>6 h
CI, Confidence interval; CMV, cytomegalovirus.
Zafar et al Cardiothoracic Transplantation
The Journal of Thoracic and Cardiovascular SurgerycVolume 141, Number 3 831
improvement in affective therapies. Therefore, in patients
surviving the first posttransplant year, the subsequent mor-
tality rate has not changed in more than 2 decades. There is
an increasing need for novel therapies focused on improv-
ing the long-term survival in these patients.
2. Toronto Lung Transplant Group. Unilateral lung transplantation for pulmonary
fibrosis. N Engl J Med. 1986;314:1140-5.
3. Grossman RF, Frost A, Zamel N, et al. Results of single-lung transplantation for
bilateral pulmonary fibrosis. N Engl J Med. 1990;322:727-33.
4. Aurora P, Edwards BL, Christie J, et al. Registry of the International Society for
Heart and Lung Transplantation: Eleventh Official Pediatric Lung and Heart/
Lung Transplantation Report—2008. J Heart Lung Transplant. 2008;27:978-83.
5. Kirk R, Edwards LB, Aurora P, et al. Registry of the International Society for
Heart and Lung Transplantation: Eleventh Official Pediatric Heart Transplanta-
tion Report—2008. J Heart Lung Transplant. 2008;27:970-7.
6. Morales DL, Dreyer WJ, Denfield SW, et al. Over two decades of pediatric heart
7. Patterson GA, Cooper JD, Dark JH, et al. Experimental and clinical double lung
transplantation. J Thorac Cardiovasc Surg. 1988;95:70-4.
8. SharplesLD,McNeil K, StewartS,etal.Risk factors for bronchiolitis obliterans:
a systematic review of recent publications. J Heart Lung Transplant. 2002;21:
9. Khalifah AP, Hachem RR, Chakinala MM, et al. Minimal acute rejection
after lung transplantation: a risk for bronchiolitis obliterans syndrome. Am
J Transplant. 2005;5:2022-30.
10. Tamm M, Sharples LD, Higenbottam TW, et al. Bronchiolitis obliterans
syndrome in heart-lung transplantation: surveillance biopsies. Am J Respir Crit
Care Med. 1997;155:1705-10.
11. Starnes VA, Bowdish ME, Woo MS, et al. A decade of living lobar lung
transplantation: recipients outcomes. J Thorac Cardiovasc Surg. 2004;127:
12. Sweet SC. Pediatric lung transplantation. Proc Am Thorac Soc. 2009;6:122-7.
13. Trulock EP, Christie JD, Edwards LB, et al. Registry of the International Society
for Heart and Lung Transplantation: Twenty-Fourth Official Adult Lung and
Heart-Lung Transplantation Report-2007. J Heart Lung Transplant. 2007;26:
14. Elizur A, Sweet SC, Huddleston CB, et al. Pre-transplant mechanical ventilation
increases short-term morbidity and mortality in pediatric patients with cystic fi-
brosis. J Heart Lung Transplant. 2007;26:127-31.
15. Griffith B, Hardesty R, Armitage J, et al. A decade of lung transplantation. Ann
16. Aris RM, Gilligan PH, Neuringer IP, et al. The effect of panresistant bacteria in
cystic fibrosis patients on lung transplantation outcome. Am J Respir Crit Care
17. Dobbin C, MaleyM,HarknessJ, etal. The impact ofpan-resistantbacterialpath-
large referral centre. J Hosp Infect. 2004;56:277-82.
18. Hadjiliadis D, Steele MP, Chaparro C, et al. Survival of lung transplant recipients
with cystic fibrosis harboring panresistant bacteria other than B cepacia, com-
pared to patients harboring sensitive bacteria. J Heart Lung Transplant. 2003;
19. Chaparro C, Maurer J, Gutierrez C, et al. Infections with Burkholderia cepacia in
cystic fibrosis: outcomes following lung transplantation. Am J Respir Crit Care
20. Aris RM, Routh JC, LiPuma J, et al. Lung transplantation for cystic fibrosis pa-
tients with Burkholderia cepacia complex: survival linked to genomovar type.
Am J Respir Crit Care Med. 2001;164:2102-6.
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832The Journal of Thoracic and Cardiovascular SurgerycMarch 2011
TABLE E1. Pretransplant diagnosis
Primary pulmonary hypertension
Primary graft failure
Primary bronchiolitis obliterans
Idiopathic pulmonary fibrosis
Pulmonary fibrosis other cause
Pulmonary vascular disease
Surfactant protein B deficiency
COPD, Chronic obstructive pulmonary disorder.
TABLE E2. Causes of death
Cause of death FrequencyPercent
Cardiovascular (myocardial infarction, cardiac
arrest, ventricular failure, cardiogenic
Primary pulmonary hypertension
Acute respiratory distress
Metastatic other specify
Primary other specify
Posttransplant lymphoproliferative disorder
Intraoperative: not hemorrhage
Multiple organ failure
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