Did you know...

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Figure 1. Current 5-year post-transplantation survival rates for kidney, liver, heart, and lung. US Dept. of Health and Human Services, 2009.

...that 2013 marks the 50th anniversary of the first human lung transplant?

In 1963, Dr. James Hardy and colleagues from the University of Mississippi transplanted the left lung of John Richard Russell, a convicted murderer who suffered from an occlusive malignant carcinoma in his left lung, advanced emphysema of his right lung, and renal failure [1]. For his contribution to science, Russell received a full pardon [2], but died 18 days after surgery. This hallmark procedure proved that lung transplantation was technically feasible. However, the 5-year post-transplant survival remains low compared to the survival rates of other organ transplants (Figure 1) [3].

In the subsequent twenty years, several attempts at lung transplantation failed. Most patients died within a few weeks due to transplant rejection, and many never left the hospital. The improvement in immunosuppressive therapies was a significant advancement to post-surgery survival. Cyclosporine A, which inhibits the production of the pro-inflammatory cytokine, Interleukin 2 [4], and subsequent T-cell activation, became available clinically in 1983 and was used in the first successful lung transplant that same year [5]. For transplant recipients, cyclosporine A remains a critical ingredient of the triple-drug immunotherapy, consisting of a calcineurin inhibitor, an antimetabolite, and a corticosteroid. This drug combination deters the onset of bronchiolitis obliterans syndrome, a form of chronic graft rejection and one of the leading causes of lung transplant-related mortality [6].

More sophisticated screening and storage techniques are critical to further increase 5-year survival. Currently, a transplant surgeon determines whether to operate solely by surveying the exterior of donor lungs [7]. Once approved, lungs can be stored in 4°C for up to 3 hours, which is a potentially damaging process [8]. Additionally, exhaustive eligibility criteria are established for both donors and recipients. Lung transplantation is absolutely contraindicated in patients with malignancy or dysfunction of another major organ system [9]. Under the current guidelines, John Russell would have never received a new lung. While several advances have been made in the field of lung transplantation, more research is necessary to further improve 5-year survival.

 

References

  1. Hardy, J.D., et al., Lung Homotransplantation in Man. JAMA, 1963. 186: p. 1065-74.
  2. Press, A., Pardon to Reward Convict in Rare Lung Transplant, in The Fort Scott Tribune. 1963: Fort Scott.
  3. Services, U.S.D.o.H.a.H. Patient Survival. 2009.
  4. Snell, G.I. and G.P. Westall, Immunosuppression for lung transplantation: evidence to date. Drugs, 2007. 67(11): p. 1531-9.
  5. Cooper, J.D., et al., Unilateral lung transplantation for pulmonary fibrosis. Toronto Lung Transplant Group. N Engl J Med, 1986. 314(18): p. 1140-5.
  6. Todd, J.L. and S.M. Palmer, Bronchiolitis obliterans syndrome: the final frontier for lung transplantation. Chest, 2011. 140(2): p. 502-8.
  7. Kron, I.L., et al., Successful transplantation of marginally acceptable thoracic organs. Ann Surg, 1993. 217(5): p. 518-22; discussion 522-4.
  8. Sanchez, P.G. and F. D'Ovidio, Ex-vivo lung perfusion. Curr Opin Organ Transplant, 2012. 17(5): p. 490-5.
  9. Orens, J.B., et al., International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant, 2006. 25(7): p. 745-55.

Author: Jamie Hill
Chief editor: Sarah Sayner, Ph.D., October 2013

 

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