Pediatric Lung Transplantation

Assoc. Prof. Figen Gülen MDEge University Medical Faculty Division of Pediatric Allergy and Pulmonologyfigen.gulen@ege.edu.tr

Transplantation

Radical treatment option for end-stage organ failure

Lung Transplantation

In spite of medical treatments; * End-stage lung disease * Life-threatening pulmonary vascular disease

1963 ; first lung transplantation

History

1950 Heart-Lung1963 Adult lung1980 Canada (J.Cooper), England,

USA (Heart-Lung) 1986 Pediatric Lung1990 Only lung (Pasque et al.)

Single lung, single lobe 1998 Turkey Ö. Oto (Heart-Lung)

2005 USA27.527 organ transplantation

1405 Lung32 Heart-Lung

The US Organ Procurement and Transplant.

Network (OPTN/SRTR 2005)

2000-2002 Pediatric Transplantation

Mallory G.B.Eur.Res.J. 2004; 24:839-45

Paul Aurora, Leah B. Edwards et al. J Heart Lung Transplant 2009; 28: 1023-30.

Paul Aurora, Leah B. Edwards et al. J Heart Lung Transplant 2009; 28: 1023-30.

Paul Aurora, Leah B. Edwards et al. J Heart Lung Transplant 2009; 28: 1023-30.

ISHLT (International Society for Heart and Lung Transplantation)

Chronic obstructive lung diseaseIdiopathic Pulm.FibrosisCystic FibrosisPrimary Pulm. HypertensionAlpha-1 antityripsin deficiencyBronchiectasisEisenmenger Synd.Re-TransplantationOthers

ISHLT. J.Hearth. Lung. Trans. 2006; 25: 745,755

Adult indications

Contraindications

AbsoluteRelative

Absolute Contraindications

Severe scoliosis, Thorax deformitySevere tracheomegaly and malasia Liver, kidney, left vent. insufficiencyActive malignancy (last 2 years)Irreversible neuromuscular diseaseActive systemic vascular disease

Absolute Contraindications Burcholderia cepacia genomovar-3 Lower respiratory infectionHepatitis B-C, HIV (unresponsive to treatment)Active viral inf.Active TuberculosisBacteriemia or septicemia

Am.J.of Transplasnt 2007;7:285-92J.Hearth Lung Transplant 2006;25:745-55

Eur .Res.J. 2004;24:839-45

Absolute Contraindications

Incompatible with medical monitoring and treatment ,Without social security ,Patients with psychiatric disorders, or non-cooperative .

Am.J.of Transplasnt 2007;7:285-92j.Hearth Lung Transplant 2006;25:745-55

Eur .Res.J. 2004;24:839-45

Relative Contraindications

Symptomatic osteopenia, osteoporosisPneumonectomyResistant and high-virulence organisms in airway (colonization) Lower respiratory infection with B.Cepacia genomovar (except genomovar 3)Severe malnutritionPleurodesis25/30 kg/m2 < BMI18/20 kg/m2 > BMIMechanical ventilation

Am.J.of Transplasnt 2007;7:285-92J.Hearth Lung Transplant 2006;25:745-55Eur .Res.J. 2004;24:839-45

Criteria for entry into the listExpected survival 6 months-2 years, New-York Hearth association

(NYHA) class III and IV levels function

NYHA Functional Classification• NYHA Class III: moderate, significant limitation in physical activity, but the rest is easy, less activity than usual causes symptoms• NYHA Class IV: severe, can not do any physical activity without any problems,orthopnea or paroxysmal Symptoms such as nocturnal dyspnea can be found at rest

Other Criterias

Patients on Technological supportNitric-oxide inhalationExtracorporeal membran oxygenation

Reviews neededBlood examination

Hemogram, HemostasisBlood groupUrea, Ions, creatininBlood glucoseLiver functionsLipidsThyroid functionsHLA typing

Radiological examinations

Chest x-rayThorax, abdominal tomographyAbdominal ultrasoundVentilation/Perfusion scintigraphySinusal tomography (for CF)

Functional ExaminationsLung

Pulmonary function tests, diffusion capacityBlood gases6 sec. walking test

HeartEKG, ECHO, bone-mineral density

Searching for InfectionsSputum, culture-antibiogramDetection of mycobacteriaPPDUrine analysisCulture for MRSAHIV, Hepatitis B and C serologyEBVChlamydia pneumoniaeVaricella zoster serology

Evaluation of malignancy

Sputum cytologyPapanicolau smearProstate-specific antigenMammographyBlood in stool

Assessment of autoimmunity

ANA, RFDNA antibodyANCACreatinin kinaseImmunoglobulins

ConsultationsDentalGastroDermatologyPsychiatryNutritionEar-Nose-Throat (ENT)Physiotherapy

Patient Selection Criterias

Cystic Fibrosis

Basic illness requirements for lung transplantation in children, adolescent and young adults

CF and BronchiectasisFEV1 < %30 and progressive declinePCO2 > 55 mmHgPO2 < 50 mmHg

increased egzazerbation despite treatment with antibiotics Refractory and / or recurrent pneumothoraxUncontrolled Hemoptysis

Am. J.of Transpl. 2007;7:285-92

Idiopathic Pulmonary Hypertension

NYHA or WHO class III-IV findings

Low response to 6 sec. walking test

Uncontrolled syncope

Hemoptysis

Right heart failure

Hearth, Lung Transplant 2006;25:745-55

Pulmonary Vascular Disease

Uncontrolled progressive pulmonary HTDeterioration of quality of lifeSevere hypoxemia

Donor Selection

ABO compatibilitySizeChest radiographyArterial blood gasesBronchoscopy

ABO compatibilitySizeChest radiographyArterial blood gasesBronchoscopy

Applied Techniques

Single lung or lobeDouble lungHeart-lung transplantation

Donors

Cadaveric (Heart-Lung, double-lung)Live (one lung, lobe)

For Children, a living donor is preferred

Ischemic time for organs to be transplanted to a maximum of 4-5 hours.

Pediatric Single Lung TranplantationIdiopatic Pulmonary Fibrosis

(isolated lung disease)Pulmonary Hypertension (isolated)

Pediatric Heart-LungSevere heart failure including Left ventriclepulmonary hypertension + structural heart defects untreatable with surgery

Bilateral Lung Transplantation

Pulmonary FibrosisPrimary pulmonary hypertensionpulmonary hypertension + heart defects untreatable with surgeryInterstitiel lung diseaseCystic FibrosisSurfactant protein B deficiencyAlveolar proteinosisBronchiolitis obliterans

TCH LUNG TRANSPLANT TEAMPhysiciansGeorge Mallory, M.D. DirectorE. Dean McKenzie, M.D. Surgical DirectorOkan Elidemir, M.D. Pediatric Transplant PulmonologistJeff Heinle, M.D. Pediatric Cardiothoracic SurgeonDavid Morales, M.D. Pediatric Cardiothoracic SurgeonDean Andropolous, M.D. Pediatric CT Anesthesiologist

Additional Clinical PersonnelPegg Dobmeier, RN, BSN Transplant CoordinatorTonya Jack, RN, BSN Transplant CoordinatorBrady Moffet, Ph.D. Transplant Pharmacist Michelle Lawson, LMSW Social Work Katherine Rushing, CCLS Child Life SpecialistMichele Burns, RD NutritionistPatricia Harris, RRT Pulmonary Diagnostic LabDanita Czyzewski, Ph.D. PsychologyKatie Wilkinson, RPT Physical TherapySteve Habetz, RPT Physical Therapy

TCH LUNG TRANSPLANT TEAMTCH LUNG TRANSPLANT TEAM

Pre-surgery induction (triple drug) PO cyclosporine 300-400 ng/ml orIV-PO tacrolimus 10-15 ng/mlIV azathioprine 2-3 mg/dIV-PO mycophenolate mofenil 15mg/kg BIDIV prednisolon 0.5-1 mg/kg

(Cyclosporine + Azothioprine + Steroid)for 3 months

Continuation with Tacrolimus + MMF + Prednisolon

Am.J.of transplant 2007;7:285-92

AntimicrobialsExcept CF

1. jenerasyon sefalosporinCF

IV 2 antipsödomonalAccording to culture

Aspergillus Fumigatus :I.V. Low-dose amphotericine-BIf CMV (+) IV gancyclovirPneumocystis CariniiTrimethoprim-sulfametaxole

Complications

SurgeryAnastomotic strictures Gastrointestinal dysmotility 50% ArrhythmiaInfectious1-6 months viral, fungal infection (24-46%)1-12 months CMV, EBV, P.cariniiLate stage bacterial infection

Post-dilatationBronchial AnastomoticStricture

Immunologic ComplicationsAcute rejection: 1 week-1 monthAsymptomaticFever, dyspnea, hypoxiaX-ray, bilateral infiltrasyonDecline in FEV1 and FVC

Diagnosis: Bronchoscopy, BAL,TB. Biopsy (A0-A4 grade)

Chronic rejection: Several months later

Am.J.of Transplant 2007;285-92

Acute rejectionOften seen after transplantation Reported over 50%Symptoms of fever and malaise However, many patients with minimal symptomsTransbronchial biopsy:

sensitivity specifity

Acute rejection %88 %91Chronic rejection %60 %100

Bronchiolitis ObliteransThe most feared complication of long-term50% in the first five yearsPost-transplant deaths: 40% in the first yearDevelopment is not clear Lower risk of developing in live-donortransplant Diagnosis: biopsy, HRCT, Vent. / Perf. Scintg.Treatment: immunosuppressive

Eur.resp. J. 2004;24:839-45Am.J.of Transplant 2007;7:285-89

Followed by transbronchial biopsy

Malignancy

6.5% in the first 1 yearIn five years, 8.5%LymphomaEBV infection is a riskTreatment: reduction of immunosuppressionCD20 monoclonal antibody

Survival

mean /yearPediatric all ages 3.5Adolescent 5.4Adult 3.8Infant 7.1

J.of Hearth Lung transplant 2002;21:827-40

Paul Aurora, Leah B. Edwards et al. J Heart Lung Transplant 2009; 28: 1023-30.

Early death:% 56 Acute rejection% 8 Infection

Late death:% 62 Bronchiolitis Obliterans% 22 Infection% 14 Malignancy

Ann Surgery 2002;236:270-76

Paul Aurora, Leah B. Edwards et al. J Heart Lung Transplant 2009; 28: 1023-30.

8 April 2009

M.P.Birth date: 14.06.1994 Admission date: 07.04.2008Complaints: CoughDifficulty breathingWheezing

Diagnosis: Bronchiolitis obliterans+ Bronchiectasis+ Pulmonary Hypertansion

Pulmonary Function Tests

Before Bronchodilat. After Bronchodilat.

FVC 28 % 30 %FEV 1 23 % 24 %

MEF 25 - 75 12 % 13 %

Blood gases: pH: 7.44 pO2: 64 pCO2:48 HCO3: 29 Sat: % 93

DOUBLE - LUNG TRANSPLANTATION

08.04.2009

Postop 15th minute

Treatment

Prednisolon

Mycophenolate Mofetil

Cyclosporine

Basiliximab

Postop 24th hours

Postop 48th hours

Postop 19th day

Post op 6th week

Postop 6th week

Postop 12th month

Postop 12th month

Problems in one year

CMV infection (two times)

Diarrhea (parasytic inf)

Psychiatric problems

Lung Transplantation,is a promising treatment modality despite

it’s all difficulties.Perhaps the most dramatic response;

March 2009 March 2010

Ege Heart-Lung Transplantation Team Adult; Heart and Vascular Surgery

CardiologyPulmonologyThoracic Surgery

Pediatrics; Pediatric SurgeryPulmonologyCardiology

Others: Infectious DiseasesPathologyPhysiotherapyPsychology

Ege Heart-Lung Transplantation Team Adult; Heart and Vascular Surgery

CardiologyPulmonologyThoracic Surgery

Pediatrics; Pediatric SurgeryPulmonologyCardiology

Others: Infectious DiseasesPathologyPhysiotherapyPsychology

Thank you Thank you

for your attentionfor your attention

Assoc. Prof. Figen GAssoc. Prof. Figen Güülen MDlen MD

figen.gulen@ege.edu.trfigen.gulen@ege.edu.tr