Pulmonary transplantation—is it a long-term solution?
Editorial

Pulmonary transplantation—is it a long-term solution?

Sivaveera Kandasamy, Christine L. Lau, Alexander Sasha Krupnick

Division of Thoracic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA

Correspondence to: Alexander Sasha Krupnick, MD. Division of Thoracic Surgery, Department of Surgery, University of Maryland School of Medicine, 29 South Greene Street, Suite 504, Baltimore, MD 21201, USA. Email: AKrupnick@som.umaryland.edu.

Comment on: Miggins JJ, Reul RM Jr, Barrett S, et al. Twenty-year survival following lung transplantation. J Thorac Dis 2023;15:2997-3012.


Keywords: Double lung transplantation; multiple decade survival; chronic lung allograft dysfunction (CLAD)


Submitted Jun 17, 2023. Accepted for publication Jul 21, 2023. Published online Jul 27, 2023.

doi: 10.21037/jtd-23-956


The history of lung transplantation is a testament to the remarkable strides made in medicine. Through research, surgical innovation, and advancements in immunosuppression and immunomodulation, lung transplantation has evolved from a daring experiment to a life-saving procedure that offers hope to patients suffering from end stage lung diseases. While significant strides have been made in the field, improving long-term survival rates remains a key challenge.

It is interesting to note that while the first human to human heart transplant by Christiaan Barnard received international fame, the first human to human lung transplant did not garner as much attention. This was performed in 1963 by James Hardy at the University of Mississippi (1) in a patient diagnosed with advanced lung cancer. Despite the surgery itself being a success, this day in history was overshadowed by the tragic death of Medgar Evers, a prominent civil rights activist, who was shot on the driveway of his home and was brought to the University of Mississippi. Unfortunately, attempts at resuscitation were unsuccessful, and the first human lung transplant only found its way to the bottom corner of the morning newspaper’s front page (2). While the patient’s survival was short lived and only lasted eighteen days, this historic endeavor laid the foundation for subsequent efforts (3).

The first successful lung transplantation was reported in 1971 by Fritz Derom in Belgium (4). The patient was diagnosed with end stage silicosis and survived approximately 10 months post-transplant; however, he had spent most of his postoperative life in the hospital, making the palliative benefit of the transplant questionable (5). Lung transplants underwent another breakthrough in 1981 with double lung transplants with tracheal anastomoses.

Up until this time, all lung transplantations performed had been single lung transplants. Bruce Reitz and his team at Stanford University performed that first successful en bloc heart-lung transplant in a 45-year-old woman diagnosed with primary pulmonary hypertension (6). Five years later, Alexander Patterson and Joel Cooper performed the first successful double lung transplant in a 42-year-old woman with emphysema secondary to alpha1-antitrypsin deficiency (7). Despite the success, surgeons soon realized that en bloc lung transplantation with tracheal anastomosis had high rates of dehiscence. As a result, sequential double lung transplantation emerged with anastomosis being performed at the mainstem bronchus level. Interestingly, this technique, still used in practice today, was first described by Henri Metras in 1950 (8). Bilateral lung transplants have been recognized to show improved survival and lower incidence of bronchiolitis obliterans syndrome (BOS) (9-11).

While the advancements in surgical technique were key in contributing to better early survival, this gave rise to long term complications like chronic rejection. Perhaps nothing had a greater impact in this avenue than immunosuppression. The emergence and use of agents such as cyclosporine and tacrolimus, and induction therapy, were extrapolated from its benefits seen in patients who had undergone other solid organ transplants (12).

As the field of lung transplantation has continued to evolve past its nascent stages, we have now reached an era where we are not limited by the technical aspect of this operation, but rather other factors. Patients who underwent lung transplantation before 2010 had a one- and five-year survival of 85% and 59%, respectively (11). Historically, most efforts focused on improving survival in the first post-transplant year. While there have been some significant milestones which have contributed to improving survival like the implementation of the Lung Allocation Score, utilizing donation after circulatory death (DCD) donors and using ex-vivo lung perfusion (EVLP), decline in survival after year one points out that chronic lung allograft dysfunction (CLAD) remains a major barrier in the field. An analysis of the recipient, donor, and operative characteristics in a cohort of multiple decade survivors is key in helping us understand factors associated with sustained long term graft function.

The current study by Miggins et al. is the first to explore these factors in transplant recipients who have survived multiple decades (13). Their results have redemonstrated what we know thus far regarding single versus bilateral lung transplants. Although there are no significant differences in postoperative complications between the two cohorts, there have been a plethora of recent studies that have associated better long-term survival and postoperative lung function in bilateral recipients (14). BOS, a subtype of CLAD, continues to be the leading cause of late mortality and morbidity in recipients, and bilateral recipients have shown to have a lower incidence compared to single recipients (15). Interestingly, the authors demonstrated a significant drop in single lung transplant survival in the 20 plus year group.

Perhaps the most important contribution of this study are the findings which raise several immunological questions and beg for further investigation. Minimal human leukocyte antigen (HLA) mismatch and female-to-female gender match was associated with increased likelihood of multiple decade survival. While the literature regarding HLA mismatch’s association with CLAD is well documented (16), female-to-female donor-recipient matching in lung transplantation remains controversial. Prior observations have shown female recipients to have significantly improved survival. This study identifies female-to-female gender match associated with increased likelihood of 20 plus year survival. The development of antibodies against human minor histocompatibility antigens encoded on the Y chromosome (H-Y antibodies) has been studied in recipients of other organ transplants which showed a correlation with acute rejection, however, the Y chromosome influence will require further investigation on its role in lung transplantation (17,18).

The molecular mechanism by which donor smoking affects long term survival in recipients is another venue worth investigating. It is interesting note that retrospective studies have shown donor lungs with a >20-pack-year smoking history having no significant effect on the incidence of BOS (19). However, donor smoking history has been associated with decreased recipient survival (20). This study has identified donor cigarette use as a moderate long-term risk factor independent of its short-term effect (13), suggesting that carbon black from smoking may have a hand in the CLAD.

The pursuit of improving lung transplant survival rates requires a multifaceted approach that encompasses advancements in immunosuppressive strategies, precision medicine, donor-recipient matching, and collaborative care. Collaboration ensures a comprehensive evaluation to select candidates with the best chances of long-term success. This also helps strive toward a future where lung transplantation becomes an increasingly successful and transformative therapy, offering renewed hope and improved quality of life for individuals in need.


Acknowledgments

Funding: None.


Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-956/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


References

  1. Hardy JD, Webb WR, Dalton ML Jr, et al. Lung homotransplantation in man. JAMA 1963;186:1065-74. [Crossref] [PubMed]
  2. Panchabhai TS, Chaddha U, McCurry KR, et al. Historical perspectives of lung transplantation: connecting the dots. J Thorac Dis 2018;10:4516-31. [Crossref] [PubMed]
  3. Aru GM, Call KD, Creswell LL, et al. James D. Hardy: a pioneer in surgery (1918 to 2003). J Heart Lung Transplant 2004;23:1307-10. [Crossref] [PubMed]
  4. Derom F, Barbier F, Ringoir S, et al. Ten-month survival after lung homotransplantation in man. J Thorac Cardiovasc Surg 1971;61:835-46.
  5. Grover FL, Fullerton DA, Zamora MR, et al. The past, present, and future of lung transplantation. Am J Surg 1997;173:523-33. [Crossref] [PubMed]
  6. Reitz BA, Wallwork JL, Hunt SA, et al. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med 1982;306:557-64. [Crossref] [PubMed]
  7. Patterson GA, Cooper JD, Goldman B, et al. Technique of successful clinical double-lung transplantation. Ann Thorac Surg 1988;45:626-33. [Crossref] [PubMed]
  8. Metras D. Henri Metras: a pioneer in lung transplantation. J Heart Lung Transplant 1992;11:1213-5; discussion 1215-6.
  9. Weiss ES, Allen JG, Merlo CA, et al. Factors indicative of long-term survival after lung transplantation: a review of 836 10-year survivors. J Heart Lung Transplant 2010;29:240-6. [Crossref] [PubMed]
  10. Kulkarni HS, Cherikh WS, Chambers DC, et al. Bronchiolitis obliterans syndrome-free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis. J Heart Lung Transplant 2019;38:5-16. [Crossref] [PubMed]
  11. Bos S, Vos R, Van Raemdonck DE, et al. Survival in adult lung transplantation: where are we in 2020? Curr Opin Organ Transplant 2020;25:268-73. [Crossref] [PubMed]
  12. Bhorade SM, Stern E. Immunosuppression for lung transplantation. Proc Am Thorac Soc 2009;6:47-53. [Crossref] [PubMed]
  13. Miggins JJ, Reul RM Jr, Barrett S, et al. Twenty-year survival following lung transplantation. J Thorac Dis 2023;15:2997-3012. [Crossref] [PubMed]
  14. Yu H, Bian T, Yu Z, et al. Bilateral Lung Transplantation Provides Better Long-term Survival and Pulmonary Function Than Single Lung Transplantation: A Systematic Review and Meta-analysis. Transplantation 2019;103:2634-44. [Crossref] [PubMed]
  15. Costa J, Benvenuto LJ, Sonett JR. Long-term outcomes and management of lung transplant recipients. Best Pract Res Clin Anaesthesiol 2017;31:285-97. [Crossref] [PubMed]
  16. Yamada Y, Langner T, Inci I, et al. Impact of human leukocyte antigen mismatch on lung transplant outcome. Interact Cardiovasc Thorac Surg 2018;26:859-64. [Crossref] [PubMed]
  17. Tan JC, Wadia PP, Coram M, et al. H-Y antibody development associates with acute rejection in female patients with male kidney transplants. Transplantation 2008;86:75-81. [Crossref] [PubMed]
  18. Matthews JC, Aaronson KD. Sex matters, but to what clinical avail? Circ Heart Fail 2009;2:389-92. [Crossref] [PubMed]
  19. Taghavi S, Jayarajan S, Komaroff E, et al. Double-lung transplantation can be safely performed using donors with heavy smoking history. Ann Thorac Surg 2013;95:1912-7; discussion 1917-8. [Crossref] [PubMed]
  20. Chaney J, Suzuki Y, Cantu E 3rd, et al. Lung donor selection criteria. J Thorac Dis 2014;6:1032-8. [Crossref] [PubMed]
Cite this article as: Kandasamy S, Lau CL, Krupnick AS. Pulmonary transplantation—is it a long-term solution? J Thorac Dis 2023;15(8):4148-4150. doi: 10.21037/jtd-23-956

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