Table Of ContentREVIEW
Pediatric lung transplantation: 10 years of experience
Priscila C. L. B. Camargo,I Eduardo Z. S. Pato,II Silvia V. Campos,I Jose´ E. Afonso Jr.,I Rafael M. Carraro,I
Andre´ N. Costa,I Ricardo H. O. B. Teixeira,I Marcos N. Samano,III,* Paulo M. Peˆgo-FernandesII
IHospitaldasCl´ınicasdaFaculdadedeMedicinadaUniversidadedeSa˜oPaulo(HCFMUSP),HeartInstitute(Incor),PulmonologyDivision,Sa˜oPaulo/SP,
Brazil.IIFaculdadedeMedicinadaUniversidadedeSa˜oPaulo(USP),Sa˜oPaulo/SP,Brazil.IIIHospitaldasClı´nicasdaFaculdadedeMedicinadaUniversidade
deSa˜oPaulo(HCFMUSP),HeartInstitute(Incor),ThoracicSurgeryDivision,Sa˜oPaulo/SP,Brazil.
Lungtransplantationisawell-establishedtreatmentforadvancedlungdiseases.Inchildren,thediseasesthat
most commonly lead to the need for a transplantation are cystic fibrosis, pulmonary hypertension, and
bronchiolitis.However,thenumberofpediatriclungtransplantationsbeingperformedislowcomparedwith
thenumberof transplants performedintheadult agegroup. Theobjective ofthisstudy was todemonstrate
ourexperiencewithpediatriclungtransplantsovera10-yearperiodinaprograminitiallydesignedforadults.
KEYWORDS: Lung Transplantation; Pediatrics;Cystic Fibrosis;Bronchiectasis; Bronchiolitis.
CamargoPC,PatoEZ,CamposSV,AfonsoJr.JE,CarraroRM,CostaAN,etal.Pediatriclungtransplantation:10yearsofexperience.Clinics.
2014;69(S1):51-54.
E-mail:[email protected]
*correspondingauthor
Tel.:55112661-5248
& INTRODUCTION The aim of this study was to describe the pediatric lung
transplantationexperiencesattheHeartInstitute(InCor)of
Lung transplantation (LTx) is now a well-established
Faculdade deMedicina daUniversidade de Sa˜oPaulo.
therapyfortreatingvariouschroniclungdiseasesthatlead
tosevererespiratoryfailure.LTxhasimprovedsignificantly
& PATIENTS AND METHODS
since it began in 1963 with James Hardy (1). An increasing
numberofstudieshavefocusedonstudyingtheindications, Aretrospectiveanalysisofthemedicalrecordsofpatients
techniques, immunosuppressive drugs, and criteria for undergoing lung transplantation at the Heart Institute
donation. The first pediatric LTx occurred in 1987 in a 16- (Incor) of Hospital das Cl´ınicas da Faculdade de Medicina
year-old boywith familial pulmonary fibrosis(2). de Sa˜o Paulo was performed for the period from January
The annual number of pediatric lung transplants per- 2003toOctober 2013.
formed is significantly lower than that of adult transplant
surgeries performed each year. According to a 2013 report & RESULTS
from the International Society of Heart and Lung Trans-
plantation,from1986toJune2012,inpatientsyoungerthan FromFebruary2003toOctober2013,192lungtransplants
18 years, 1875 lung transplants and 667 double heart and were performed at our institution (11 patients 18 years
lungtransplantationswerereported(3),whereastherewere old and younger). The recipient distribution by age and
3640transplanted adultsin 2011(4). diagnosisis showninFigure1.
ThemostcommonindicationforLTxinpatientsupto18 All 11 pediatric patients underwent bilateral sequential
years old is cystic fibrosis (3), a fact that is also demon- LTx;twopatientsrequiredcardiopulmonarybypassduring
strated in this study. Other indications for LTx include surgery. To date, the longest surviving pediatric transplant
bronchiolitis obliterans, bronchiectasis, pulmonary arterial patient underwent surgery 5 years ago when he was 11
hypertension, idiopathic fibrosis, interstitial lung diseases, yearsold.
andsurfactant proteinabnormalities (5). Two patients suffered immediate postoperative death
less than one month post transplantation. The first patient,
whose initial diagnosis was idiopathic pulmonary arterial
hypertension, developed primary graft dysfunction and
died on the 4th postoperative day. This patient was six
Copyright (cid:2) 2014CLINICS–ThisisanOpenAccessarticledistributedunder years old and required cardiopulmonary bypass. The
thetermsoftheCreativeCommonsAttributionNon-CommercialLicense(http://
creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- second patient, a 17-year-old adolescent diagnosed with
commercial use, distribution, and reproduction in any medium, provided the bronchiolitis obliterans associated with secondary pulmon-
originalworkisproperlycited. aryhypertension,alsounderwentcardiopulmonarybypass;
Nopotentialconflictofinterestwasreported. the patient developed refractory hemodynamic instability
DOI:10.6061/clinics/2014(Sup01)10 anddied threedays post-surgery.
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PediatricLungTransplantation CLINICS2014;69(S1):51-54
CamargoPCLBetal.
Figure1-Distributionofrecipientsaccordingtoageanddiagnosis.
One patient with an initial diagnosis of bronchiectasis disease (4,5). Furthermore, in Brazil, the prevalence of
died three years after undergoing transplantation for bronchiectasis (notsecondarytocysticfibrosis)isconsider-
chronicgraftdysfunctionwithclinicalrestrictivesyndrome. able, andthis conditionfrequently requires LTx.
A 16-year-old patient with an initial diagnosis of post- Intheadultpopulation,themainindicationsareemphy-
infectiousbronchiolitisobliteranssyndromelaterdeveloped semaand idiopathicpulmonary fibrosis(4).
obliterative bronchiolitis and underwent retransplantation The pediatric contraindications for the procedure are
three yearsafterthe initial procedure. identical to those in the adult population and include
In our institution, induction therapy is performed systemicdiseaseswithextrapulmonarycomplications,mali-
with 10mg/kg intravenous methylprednisolone, with gnancy, HIV infection, and severe renal impairment. The
basiliximab in the case of initial suppurative disease. The absence of social support, transportation issues, or poor
maintenance immunosuppression combines corticosteroids adherence to treatment are also important conditions that
(prednisone), calcineurin inhibitor (cyclosporine or tacroli- preclude LTx (7).
mus), and a cellular activation inhibitor (azathioprine or The number of pediatric transplants performed in our
mycophenolate sodium). study group, although small, corresponded to approxi-
The complications related to the immunosuppressive mately 5.7% of the total number of transplants performed,
regimenwereinfection(inthemajorityofcases)andrever- whichdidnotdifferfromtheliterature(3).Thesurvivalrate
sible posterior leukoencephalopathy (one case) in a patient was also similar to that of the international registry, but a
initially diagnosed with cystic fibrosis. This patient was on longer follow-up is necessary, as illustrated by the patient
cyclosporineandshowedneurologicalsymptomseightdays with a longer follow-up who underwent surgery 5 years
after the procedure, progressing to acute subdural hemor- earlier.
rhage.Currently,hehasmotorneurologicaldeficitwithout Thelownumberofdonorsandviableorgansfordonation
other complications. is a significant complicating factor that has affected the
Inourstudy,themostcommoninfectionfoundafterthefirst pediatric andadult LTx program.
month of transplant was due to citomegalovirus (CMV), As in the adult population, there are three main types
followedbyrespiratoryviralinfectionsandbacterialinfections. of postoperative complications: immediate complications,
Figure 2 shows the survival rate based on the time after occurring in the first days after transplantation; early com-
transplantation forpatients 18yearsold andyounger. plications, occurring within three months posttransplanta-
tion; andlatecomplications (8).
& DISCUSSION The immediate postoperative complications are hyper-
acute rejection, primary graft dysfunction, reperfusion
LTxisawell-establishedtherapyforpatientswithchronic injury, and surgical complications, such as anastomotic
lung disease and end-stage vascular pulmonary disease. dehiscence andbleeding.
Indications for LTx in the pediatric population are rare Hyperacute rejection is an uncommon condition. Today,
becauseterminalillnessesinthisagegroupareuncommon virtual crossmatching performedpreoperatively inpatients
(5).Mostpatientsyoungerthan18yearswhoundergolung withahighreactivepanelidentifiesanypossibleincompat-
transplantationareolderthan11years(3,6),whichwasalso ibility that could preclude transplantation between the
found in ourstudygroup. recipient and donor. Hyperacute rejection has a poor
The main indications for LTx in the pediatric population prognosis, and treatment should be started immediately
are pulmonary cystic fibrosis, interstitial lung disease if the prospective crossmatch is positive. The treatment
associatedwithpulmonaryfibrosis,andcongenitalvascular consists of plasmapheresis in the operating room and
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CLINICS2014;69(S1):51-54 PediatricLungTransplantation
CamargoPCLBetal.
Figure2-SurvivalCurve–KaplanMeier.
during the postoperative period, with the administration can be present during the entire posttransplant follow-
of intravenous immunoglobulin and thymoglobulin as an up period. The use of maintenance medications has other
additional potential indication for retransplantation (8,9). undesirableeffects,includingmetabolicchanges(hypergly-
Anotherimportantcomplicationisprimarygraftdysfunc- cemia and dyslipidemia) and nephrotoxicity. In our study
tion,whichoccurredinoursettingandcanoccurwithin72 group, one patient had reversible posterior leukoence-
hourspost-surgery.Primarygraftdysfunctionisdefinedby phalopathy, a disease that is often associated with the use
alowrelationshipbetweenPaO2andFiO2,withorwithout of calcineurin inhibitors and that has variable outcomes
radiographic changes. The complication is described in (16,17). It involves a wide spectrum of neurological
Table 1. International data show that cardiopulmonary manifestations, such as a decreased level of consciousness,
bypass is used more frequently in pediatric LTx compared seizures, and visual disturbances that are frequently
withadultLTx,anditsuseisrelatedtothedevelopmentof associated with ischemic changes mainly in parietal and
primary graft dysfunction, smoking status of the donor, occipital lesions, as evidenced by MRI. The reversibility of
presenceofreperfusioninjury,andbodymassindexofthe lesions is case dependent. Patient management usually
recipient (8,10,11). In acute respiratory distress syndrome, consists of reducing or changing the calcineurin inhibitor.
clinical management consists of protective ventilation Ourcaseshowedreversibilityofthechangesaftertheinitial
and, in some cases, the use of extracorporeal membrane change in the immunosuppressant agent, but the patient
oxygenation (10,12,13). developed hemorrhagic transformation and persistent
Acuterejection,infection,sideeffectsofimmunosuppres- motor deficiency.
sive drugs, and surgical complications, such as stenosis of Bronchiolitis obliterans syndrome is the main late
the bronchial anastomosis, are some immediate postopera- complication; it corresponds to chronic graft dysfunction.
tive complications; they frequently occur in the first three Bronchiolitisobliteranssyndromeisdefinedbya20%drop
months afterLTx. intheforcedexpiratoryvolume(FEV1)valueinonesecond
Clinically, diagnosing acute rejection and respiratory compared with the patient’s baseline, and it is diagnosed
infections can be challenging, and they require different using the best three FEV1 values previously taken after
treatments. The diagnosis of acute rejection is made using thedevelopmentoffixedairflowobstructiononspirometry
histological findings that show perivascular mononuclear and in the absence other factors that may influence the
cellinfiltrate.Theintensityandextentoftheacuterejection collection method (18). The differential diagnosis includes
determinesitsclassification(14).Whenindicated,treatment other causes of FEV1 decline, such as anastomotic stenosis
consists of adjusting the immunosuppression, including or respiratory infections. In some cases, the patient may
changingorincreasingthedoseoftheimmunosuppressive present with severe dysfunction and end-stage pulmonary
maintenanceregimen,administeringhighdosesofcorticos- disease, and any indication for retransplantation should be
teroids (in some cases), and using intravenous thymoglo- carefully evaluated (5). In our study group, retransplanta-
bulin in more severe or refractory cases (15). The infection tionwasindicated threeyearsafter thefirstprocedureina
treatment is basedon etiological agents. patientwho underwent transplantation at age16.
Infectionsareoftenrelatedtotheuseofimmunosuppres- The indications for LTx in a pediatric population are
sivedrugs,andinfectionsareonetypeofcomplicationthat less common than those in an adult population. Certain
Table1- Classification of Primary graft dysfunction -Adaptedfrom ISHLT(International Societyof Heart andLung
Transplantation Registries) (10).
Grades PaO/FiO Persistantpulmonaryinfiltrationatradiographicimagewithpulmonaryedema
2 2
0 .300 Absence
1 .300 Present
2 200-300 Present
3 ,200 Present
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PediatricLungTransplantation CLINICS2014;69(S1):51-54
CamargoPCLBetal.
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