Lung Transplantation

Principles and Practice

Wickii Vigneswaran, Edward Garrity, John Odell, Wickii Vigneswaran, Edward Garrity, John Odell

• Publisher: CRC Press
• Year: 2016
• ISBN:
  9780429586408
• Edition: 1
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

Lung Transplantation: Principles and Practice covers the current practice in donor and recipient management as well as current treatment strategies and outcomes. With 39 chapters from international experts in the field, this book covers the current practice in donor and recipient management as well as current treatment strategies and outcomes. It discusses significant advances achieved in the past decade in areas such as donor allocation, organ preservation and management, recipient selection, management and support, surgical and critical care techniques, immune suppression, and infection prophylaxis. Specific instances of pulmonary disease that commonly necessitate lung transplantation are also covered.

PART 1

General Topics

1 History of lung transplantation

Joel D. Cooper and Thomas M. Egan

2 Immunology of lung transplantation

Adam S.A. Gracon and David S. Wilkes

3 Ethical considerations in transplantation: A focus on lung transplantation

Baddr A. Shakhsheer, Sean C. Wightman, Savitri Fedson, and Mark Siegler

4 Indications for lung transplantation and patient selection

Joshua S. Mason, Julia B. Becker, and Edward R. Garrity Jr.

5 Recipient management before transplantation

Gundeep S. Dhillon and David Weill

1

History of lung transplantation

JOEL D. COOPER AND THOMAS M. EGAN

Introduction

Unique issues associated with lung transplantation

Experimental animal transplantation

Human lung transplantation

The first 10 years

The second 10 years—success remained elusive

Bronchial anastomotic complications—the Achilles’ heel

Bronchial ischemia

Successful unilateral lung transplantation

En bloc double-lung transplantation

Sequential bilateral lung transplantation

Successful unilateral lung transplantation for COPD

Growth of lung transplantation

Improvement in care

Allocation of donor lungs

Involvement of the International Society for Heart and Lung Transplantation

Lung graft dysfunction

Immunosuppression

Lung preservation

Ex vivo lung perfusion

Additional sources of donor lungs

Summary

Acknowledgment

References

What’s past is prologue

William Shakespeare

The Tempest

INTRODUCTION

Shakespeare’s aphorism applies to the history of organ transplantation in general and to the history of lung transplantation in particular. The request to prepare this chapter, which came shortly after the 30th anniversary of our initial long-term success with lung transplantation, provided a timely opportunity to reflect not only on the evolution of lung transplantation during the period before clinical success but also on the 30 years since (Table 1.1). It is humbling to reflect on how many investigators have been engaged in this endeavor and how many obstacles had to be overcome. Even now, the definition of what will ultimately be considered true success—and where on the path to that destination we now stand—is unclear. We hope that in the future, when tolerance to donor organs can be induced and decades-long improved quality of life after transplantation becomes the rule, all progress to date will be viewed as but the prologue of the past.

Historical references to the concept of human organ transplantation date back centuries and often cite the third century twin saints Cosmas and Damian, who are credited with the miraculous transplantation of the black leg of a deceased Ethiopian onto the body of a white recipient whose leg required amputation. This legend, which was memorialized by a famous painting, may seem fanciful, but no more so than the actual feat accomplished in the 1940s by the Russian physiologist Demikhov, who transplanted the head of one dog onto the neck of a second dog, with both the host and the donor head remaining alive and active for several days. It was Demikhov as well who experimented with canine pulmonary lobe transplantation and with heart-lung transplantation well before the era of cardiopulmonary bypass.¹ His technical prowess owed much to the prior work of Alexis Carrel, the French physiologist who won the Nobel Prize in 1912 for his pioneering work in developing techniques for end-to-end anastomosis of blood vessels and its use in the transplantation of whole organs.² In fact, the first “thoracic” organ transplant was described by Carrel in 1907, when he and his colleague Charles Guthrie performed a heterotopic heart-lung transplant onto the neck of a cat. When the graft died on the third day, Carrel attributed this to technical anastomotic problems, but he was probably witnessing a manifestation of acute rejection.³

Table 1.1 Timeline of seminal events in the history of lung transplantation

1907	Guthrie and Carrel—heterotopic heart-lung transplant
1940s–1950s	Demikhov—lobar transplants
1950s	Juvenelle, Metras, Hardy, and Veith—experimental canine lung transplant
1963	Hardy—first human lung transplant
1968	Derom—10-month survival
1981	Reitz et al.—first successful heart-lung transplant
1983	Cooper et al.—first successful single-lung transplant
1986	Cooper et al.—first successful double-lung transplant
1986	Start of Organ Procurement and Transplantation Network (OPTN); United Network for Organ Sharing (UNOS) becomes contractor
1988–1995	Growth of lung transplant programs in the United States and globally
1999	Institute of Medicine report, Final Rule (2000)
2001	Steen—First lung transplant after ex vivo lung perfusion
2005	Introduction of the lung allocation score system in the United States

The final proof that an organ from one human could be transplanted into another with long-term clinical benefit was demonstrated by the first successful human kidney transplant, which was performed by Dr. Joseph Murray and colleagues in 1954.⁴ The donor and recipient were identical twins, thus eliminating the unsolved problem of organ rejection. This accomplishment, for which Dr. Murray was awarded the Nobel Prize in 1990, clearly demonstrated the potential for treatment of end-stage disease by means of organ transplantation. Nothing dramatized this potential more than the occasion of the first human heart transplant, conducted by Dr. Christiaan Barnard in December 1967. Although the recipient succumbed to pneumonia 18 days later, postoperative photographs of the recipient looking well and cheerful captivated the attention of the world.

UNIQUE ISSUES ASSOCIATED WITH LUNG TRANSPLANTATION

By 1980, liver and heart transplants had joined renal transplants as accepted options for treating end-stage organ failure. However, progress in lung transplantation lagged, and expectations were dampened by lack of success in the laboratory and in the clinical arena.

It became obvious that lung transplantation posed unique obstacles. The lung is the only organ transplanted without reattachment of its systemic arterial blood supply (the bronchial arteries). Thus, one of the major anastomoses—the bronchial anastomosis—is rendered ischemic; it is also open to the external environment and very prone to infection. In addition, the lung is a fragile organ prone to injury and infection and also significantly more susceptible to rejection than other major organs.

Most experimental lung transplantations were conducted on a canine model. However, the dog, like other subprimate animals, is dependent on the Hering-Breuer reflex to maintain central respiratory control. With total denervation of both lungs, such as would occur with bilateral or unilateral lung transplantation and removal of the opposite lung, the dog cannot survive because of loss of the normal respiratory control mechanism. This problem made it difficult to assess the function of an experimentally transplanted lung when the animal was removed from the ventilator following transplantation. Only in a primate model, a complex and expensive undertaking, can the recipient animal remain alive for days or weeks solely on the function of transplanted lungs. In addition, as the authors can well attest, lung transplantation in a canine model is technically more challenging than in humans, partly because the atrial anastomosis tends to accumulate blood clots if there is any gap in the endothelial-to-endothelial apposition of the atrial anastomosis.

EXPERIMENTAL ANIMAL TRANSPLANTATION

Resection and reimplantation of a lung in a dog was initially reported by Juvenelle and colleagues in 1951. Severing and reconnection of the pulmonary artery, superior and inferior pulmonary veins, and bronchus of the right lung of the dog was undertaken to evaluate the effect of denervation on the postulated pulmonary reflex known as bronchospasm, whose “existence has yet to be proved.”⁵ In 1950, Metras in Marseilles reported a technique for canine allotransplantation.⁶ The technique involved performing the venous anastomosis by using a cuff of atrium surrounding the two pulmonary veins rather than separate individual vein-to-vein anastomoses. This important technical contribution continues to be used. Metras reported survival for a matter of days at best, with death attributed to either infection or rejection.

Early attempts at suppressing rejection included adrenocorticotropic hormone, cortisone, total body irradiation, and splenectomy. Hardy observed that survival in dogs undergoing single-lung transplantation could be prolonged for more than a week with the use of methotrexate and further extended to an average of 29 days when recipient animals were treated with azathioprine and cortisone.⁷

The ability of a transplanted lung to totally support an animal’s respiratory requirement was documented in the early 1960s in a model that involved ligation of the contralateral pulmo...