eMedicine Specialties > Pediatrics: Surgery > Transplantation

Lung Transplantation

Author: Albert Faro, MD, Assistant Professor, Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine
Coauthor(s): Gary A Visner, DO, Chief, Division of Pediatric Pulmonology, Associate Professor, Department of Pediatrics, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: May 30, 2008

Introduction

Lung transplantation has matured into an accepted therapeutic alternative for children with end-stage lung disease.1 More than 1500 such procedures have been performed in children worldwide. However, the phrase "children are not just small adults" holds no greater truth than in the field of lung transplantation.

The indications for transplant, the pharmacokinetics of immunosuppressants, and the complications of transplant can be strikingly different for children compared with their adult counterparts. This article is not only meant to serve as an overview of the field of lung transplantation but also highlights the unique challenges faced by pediatric lung transplant recipients, their families, and their healthcare teams. However, this article is neither exhaustive nor comprehensive because covering the entire field of lung transplantation in this space is impossible.

History of the Procedure

In 1963, James Hardy, MD, at the University of Mississippi performed the first human lung transplantation in a 58-year-old convict serving a life sentence. The patient presented with a squamous carcinoma at the left hilum. During surgery, he was also found to have an empyema. He survived for 18 days after transplantation and died from renal failure. His immunosuppression consisted of azathioprine, prednisone, and radiation therapy. Despite an ABO mismatch, no rejection was found on autopsy.

The procedure has evolved over the past 44 years, with changes in the surgical technique and the immunosuppressive regimens. Joel Cooper, MD, at the University of Toronto achieved success in 1983 with the transplantation of a single lung. The recipient lived for 6.5 years. This procedure was soon followed by successful double lung transplantation. Lastly, Bowdish et al and other groups demonstrated that living-donor lobar lung transplantation can be successfully performed.2

Frequency

According to the International Society of Heart and Lung Transplantation (ISHLT) Registry, more than 1500 lung or heart-lung transplants were performed in children as of 2006.3 In January 2005, 214 patients younger than 18 years were on the United Network for Organ Sharing (UNOS) waiting list for either lung or heart-lung transplants.

Etiology

In patients with untreatable end-stage lung disease due to various etiologies, lung transplantation warrants consideration. In children younger than 1 year, the most common causes of end-stage disease are congenital heart disease (CHD), surfactant abnormalities, and idiopathic pulmonary hypertension (IPH) and pulmonary vascular disorders. In children aged 1-10 years, end-stage lung disease due to cystic fibrosis (CF) results in approximately 36% of all lung transplants. In adolescents, that number increases to approximately 60%. Chronic lung disease of infancy, bronchiolitis obliterans (BO), congenital cardiac disease, and pulmonary fibrosis are other diagnoses that commonly lead to lung transplantation.

Presentation

The clinical presentation varies depending on the primary diagnosis. However, children who present for an evaluation for lung transplantation have end-stage lung disease with an impaired quality of life (QOL). They may present with respiratory insufficiency or respiratory failure, exercise intolerance, poor growth, hypoxemia, carbon dioxide retention, abnormal pulmonary function test findings, and frequent respiratory exacerbations that require antibiotics and/or anti-inflammatory medications. Children with underlying pulmonary vascular disorders may present with syncope, exercise intolerance, poor growth, cyanosis, and impaired QOL.

Indications

Determining which children may benefit from lung transplantation is often not straightforward; the correct timing of the referral to a transplant center is also difficult to determine. The decision to perform transplantation is based on many factors, including past experience (both center-specific and that in published reports), the scarcity of donor organs, and the specific wishes of patients and their parents or guardians. Indications for lung transplantation in children have expanded, and referral to a transplant center should be considered in virtually any child with limited life expectancy because of lung disease. However, exactly when lung transplantation should be considered during the specific disease process requires detailed attention to not only the trajectory of the underlying illness but also to psychosocial factors, such as the readiness of the patient emotionally to the demands of daily therapy and frequent procedures.

The prognosis of the patient's natural disease must first be made clear. Lung transplantation is a procedure of last resort and, when performed, should ideally provide the patient an improved likelihood of survival and an improved QOL.

Cystic fibrosis

Investigators have developed different models that attempt to predict survival for patients with CF. Initially, according to Kerem's criteria, a forced expiratory volume in 1 second (FEV1) of less than 30% was associated with an increase in the risk of death within 2 years; associated factors include decreased PaO2 levels, an increase in PaCO2 on room-air ABG findings, younger age, and female gender. Investigators later found that this model alone did not reliably predict 2-year survival in their patient populations.

In 2001, Liou and colleagues developed a model to predict the 5-year survival rate.4 The key clinical predictors of increased mortality rates included increasing age, female sex, diabetes mellitus, airway infection due to Burkholderia cepacia,5 and frequent acute exacerbations. On the contrary, an increased FEV1, increased weight-for-age Z score, pancreatic sufficiency, and airway infection due to Staphylococcus aureus seem to have a protective effect on survival.

However, this model was limited to information collected by the Cystic Fibrosis Foundation Patient Registry and, thus, did not take into account other factors that many clinicians routinely consider in evaluating a patient with CF for lung transplantation; these other factors include room-air ABG findings, the emergence of resistant organisms, the degree of exercise intolerance, and the presence of cor pulmonale. More recently, this model has been used to assess transplant benefit (see Outcome and Prognosis). 

Pulmonary vascular disease

In children, pulmonary vascular disease may be due to several etiologies, including IPH, CHD, and pulmonary vein anomalies. Therapeutic advances have dramatically changed outcomes for children with IPH. Therefore, in children with IPH, transplantation should be considered only when medical therapy fails.

Guidelines have been published for adults in whom medical management fails; New York Heart Association (NYHA) class III or IV, low exercise tolerance, uncontrolled syncope, hemoptysis, and right heart failure are useful parameters. Whether these guidelines are appropriate for children is unclear.

In children, a decreased cardiac index, elevated pulmonary vascular resistance, right atrial pressures of more than 7.4 mm Hg, and right ventricular end-diastolic pressure (RVEDP) of more than 10.4 mm Hg portend a poor survival and are indications for lung transplantation. Other factors that may be correlated with survival include von Willebrand factor levels, elevated uric acid levels, and plasma levels of brain natriuretic peptide.

Surfactant dysfunction syndromes

This group of abnormalities is associated with congenital alveolar proteinosis. The spectrum of presentation varies, with some children presenting in respiratory failure within hours of birth, and others presenting with only subtle symptoms later in life.

Bronchopulmonary dysplasia
Because patients with bronchopulmonary dysplasia (BPD) severe enough to consider lung transplantation often have associated comorbidities, BPD is a fairly infrequent indication for lung transplantation. In addition, many infants with BPD improve if given the opportunity to grow. Lung transplantation is an option for children with BPD who do not have significant comorbidities, who are on ventilatory support, who are not improving, and who have evidence of pulmonary hypertension that is unresponsive to oxygen therapy.

Ultimately, the physician who determines the timing of referral should consider the patient’s assessment of their QOL while remembering the ideal transplant window, during which the patient is medically ill enough to warrant transplantation but not quite so ill that the odds of a good outcome are unacceptably poor. Early referral to a transplant center is preferable to late referral. This provides the center the opportunity to establish a relationship with the child and family. In addition, it allows the patient time to truly understand the commitment that lung transplantation requires and allows the center to put into place any necessary measures necessary to assure an acceptable outcome.

Contraindications

Contraindications to lung transplantation vary from center to center. An absolute contraindication at one site may only be a relative contraindication at another. More importantly, the list is not static; it changes over time with the introduction of new techniques or therapies.

For instance, pleurodesis was once almost universally considered an absolute contraindication because of the potential for heavy blood loss and death. However, with the use of aprotinin to decrease bleeding intraoperatively, pleurodesis is now only a relative contraindication, depending on the pleurodesing agent. Aprotinin is now only available via a limited-access protocol. Fergusson et al reported an increased risk for death compared with tranexamic acid or aminocaproic acid in high-risk cardiac surgery.6 For more information, see the article from Medscape.

The following table lists the contraindications currently recognized by most, but not all, pediatric centers:

  •   Absolute contraindications include the following: 
    • Active malignancy
    • Active tuberculosis
    • Sepsis
    • Cerebral dysfunction
    • Severe neuromuscular disease
    • Congenital or acquired immunodeficiency syndromes (AIDS)
    • Documented, refractory nonadherence
    • Active hepatitis C infection
    • Multiorgan dysfunction
  •   Relative contraindications include the following: 
    • Pleurodesis
    • Renal insufficiency
    • Markedly abnormal body mass index
    • Chronic airway infection with multiple resistant organisms, Burkholderia cenocepacia, or Burkholderia dolosa
    • Mechanical ventilation
    • Severe scoliosis
    • Poorly controlled diabetes mellitus
    • Active collagen vascular disease

More on Lung Transplantation

Overview: Lung Transplantation
Workup: Lung Transplantation
Treatment: Lung Transplantation
Follow-up: Lung Transplantation
Multimedia: Lung Transplantation
References
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References

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Further Reading

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Keywords

lung transplantation, lung transplant, lobar transplantation, living related donation, living-donor lung transplant, deceased donor lung transplant, heart-lung transplant, lung disease, end-stage lung disease, congenital lung disease, primary pulmonary hypertension, cystic fibrosis, CF, chronic lung disease, bronchiolitis obliterans, BO, congenital cardiac disease, pulmonary fibrosis, congenital heart disease, CHD, surfactant abnormalities, idiopathic pulmonary hypertension, idiopathic pulmonary hypertension, IPH, respiratory insufficiency, respiratory failure, syncope, diabetes mellitus, cor pulmonale, congenital alveolar proteinosis, pleurodesis

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Contributor Information and Disclosures

Author

Albert Faro, MD, Assistant Professor, Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine
Albert Faro, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Transplantation, and International Society for Heart and Lung Transplantation
Disclosure: Nothing to disclose.

Coauthor(s)

Gary A Visner, DO, Chief, Division of Pediatric Pulmonology, Associate Professor, Department of Pediatrics, University of Florida College of Medicine
Gary A Visner, DO is a member of the following medical societies: International Society for Heart and Lung Transplantation
Disclosure: Nothing to disclose.

Medical Editor

Richard G Ohye, MD, Director, Pediatric Cardiac Transplantation, Fellowship Program Director, Pediatric Cardiac Surgery, Assistant Professor, Department of Surgery, Section of Cardiac Surgery, University of Michigan Medical Center
Richard G Ohye, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Chest Physicians, American College of Surgeons, Association for Academic Surgery, International Society for Heart and Lung Transplantation, and Society of Thoracic Surgeons
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Brian F Gilchrist, MD, Chief, Division of Pediatric Surgery, Tufts-New England Medical Center; Associate Professor, Department of Surgery, Tufts University School of Medicine
Disclosure: Nothing to disclose.

CME Editor

Ron Shapiro, MD, Professor of Surgery, University of Pittsburgh; Director, Kidney, Pancreas, and Islet Transplantation, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center
Ron Shapiro, MD is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, Association for Academic Surgery, Central Surgical Association, and Society of University Surgeons
Disclosure: Astellas Honoraria Speaking and teaching; Brystol Meyer Squibb StemCell Data Monitoring Committee Consulting fee Review panel membership

Chief Editor

Mary C Mancini, MD, PhD, Director of Cardiothoracic Transplantation, Professor, Department of Surgery, Louisiana State University Health Sciences Center
Mary C Mancini, MD, PhD is a member of the following medical societies: American Heart Association, American Medical Association, American Thoracic Society, Association for Academic Surgery, Association for Surgical Education, International College of Surgeons, International Society for Heart and Lung Transplantation, New York Academy of Sciences, Phi Beta Kappa, and Southern Thoracic Surgical Association
Disclosure: Nothing to disclose.

 
 
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