15. Lung Transplantation

Transplant Indications

End-stage lung disease due to any of the following:

  • COPD, idiopathic pulmonary fibrosis, cystic fibrosis most common.
  • Other diseases include other interstitial lung diseases, idiopathic pulmonary arterial hypertension, alpha 1-antitrypsin deficiency, sarcoidosis, bronchiectasis, bronchiolitis obliterans, Eisenmenger’s syndrome.
  • Retransplant uncommon though may be necessary in the setting of graft failure.

Prognosis

  • 5-year survival remains poor (51%) due to multiple etiologies, including bronchiolitis obliterans syndrome (BOS), infection, renal insufficiency, and malignancy.
    • BOS is the leading cause of morbidity and mortality after lung transplantation and 50% meet criteria for BOS at 5 years.
  • Post-transplant survival differs among pre-transplant diagnoses.
  • Median survival is 5.8 years.

Guidelines

Disease-specific guidelines for patient referral in addition to evaluating absolute and relative contraindications guide selection of appropriate lung transplant recipients. Absolute and relative contraindications are evolving, so consider discussing potential candidates with lung transplantation service (see Weill citation below for more specific details).

Complications

  • Primary graft dysfunction: ischemia-reperfusion injury and a form of ARDS/DAD that occurs within 3 days following transplant. Treat as ARDS. Potential role for inhaled nitrous oxide (iNO) and early ECMO in instances where iNO fails.
  • Airway complications: anastamotic dehiscence (complete or partial) occurring days to weeks after transplant, anastamotic stenosis occurring weeks to months after transplant, and bronchomalacia.
  • Infections:
    • Cytomegalovirus (extended valgancyclovir prophylaxis prevents CMV disease and may also prevent PTLD associated EBV, though data is limited), Aspergillus (at anastamosis site or in lung parenchyma), bacteria (often gram-negative organisms such as Pseudomonas aeruginosa), PCP (prevented with TMP/SMX prophylaxis).
    • Community-acquired respiratory viruses (CARV): common, can be severe, and can frequently trigger subsequent acute rejection and/or rapidly progressive graft failure. Thus, immunosuppression is augmented in the setting of CARV.
  • Acute rejection: symptoms are subtle (e.g., mild cough, low-grade fever, shortness of breath). Diagnose with transbronchial biopsy. Indications include new infiltrates, decline in lung function, new cough, and unexplained dyspnea. Treatment includes increasing immunotherapy and pulse steroids.
  • Chronic rejection: histologically manifests as BOS (fibroproliferation of small airways), but transbronchial biopsy has low sensitivity. Thus, bronchiolitis obliterans syndrome (unexplained and sustained decrease of 20% or more in FEV1) is used as a surrogate diagnosis in the absence of histology. Treat with augmentation of immunosuppression. Consider addition of azithromycin. Primary cause of poor long-term survival as compared to other solid-organ transplantations.
  • Malignancy: occurs in 5-10% of patients. Includes squamous cell carcinomas of skin and lips and post-transplantation lymphoproliferative disorders (PTLD) for which EBV infection post-transplant is a major risk factor.

Immunosuppressive Agents

  • Calcineurin inhibitors: cyclosporine and tacrolimus. Multiple drug interactions (e.g., macrolides, azoles, other drugs metabolized via CYP 3A4) and side effects (nephrotoxicity). Calcineurin inhibitor-associated renal insufficiency is very common among lung recipients within 5 years (creatinine >2.5 mg/dL in >30%). Monitor levels daily while hospitalized.
  • Purine synthesis antagonists: azathioprine and mycophenolate mofetil. Side effects include myelosuppression, nausea, and diarrhea. Drug levels are not typically monitored.
  • Corticosteroids: prednisone. Side effects include hyperglycemia, hypertension, hyperlipidemia, myopathy, osteoporosis.
  • mTOR inhibitors: sirolimus and everolimus. Potential role as rescue therapy in patients with renal dysfunction. Often added in patients with malignancy for its anti-neoplastic effects. Early institution associated with anastamotic dehiscence. Monitor levels. Both are metabolized by p450 system, so be aware of drug-drug interactions.

 

Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med 1999;340:1081-1091.

Christie JD, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report – 2010. J Heart Lung Transplant. 2010 Oct;29(10):1104-1118.

Costa J, Benvenuto LJ, Sonett JR. Long-term outcomes and management of lung transplant recipients. Best Pract Res Clin Anaesthesiol. 2017 Jun;31(2):285-297. doi: 10.1016/j.bpa.2017.05.006. Epub 2017 May 30. PMID: 29110800.

Fischer S, Bohn D, Rycus P et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry. J Heart Lung Transplant 2007;26:472-477.

Pierson RN.  Lung transplantation: current status and challenges. Transplantation 2006;81:1609-1615.

Vos R, Vanaudenaerde BM, et al. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Eur Respir J. 2011 Jan;37(1):164-172.

Weill D, Benden C, et. al. A consensus document for the selection of lung transplant candidates:2014—An update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015 Jan;34(1):1-15.

”What are the risks of lung transplant?” National Heart, Lung, and Blood Institute, 2011. Web. 23 March 2015. <http://www.nhlbi.nih.gov/health/health-topics/topics/lungtxp/risks>.