92 LUNG TRANSPLANTATION
Daniel R. Meldrum M.D., Azad Raiesdana M.D., Jeffrey A. Breall M.D., John W. Brown M.D.

1. What are the general types of lung transplants?

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Single, double (bilateral), and heart-lung.

2. Which human organ transplant was performed first, the heart or the lung?

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Although heart transplantation has progressed more rapidly, the first lung transplant preceded the first heart transplant.

3. Who performed the first human lung transplant? When?

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James Hardy performed the first human lung transplant in 1963; however, more than 20 years passed before lung transplantation was performed routinely in clinical practice (during that 20 year period, only 1 patient did well enough to leave the hospital). This delay was caused by initial graft failure secondary to inadequate organ preservation, long ischemic times, lack of good immunosuppressive agents, and technical difficulties (primarily with the bronchial-not the vascular-anastomoses).

4. Who is a candidate for a lung transplant?

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Candidates include patients with no other medical or surgical alternative who are likely to die of pulmonary disease within 18 months, are younger than 65 years, are not ventilator dependent, and do not have a history of malignancy. Psychological stability in the recipient is also important.

5. What are the most common indications for single lung transplant?

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* Emphysema (40%)
* Idiopathic pulmonary fibrosis (20%)
* Alpha-1 antitrypsin deficiency (11%)
* Primary pulmonary hypertension and pulmonary hypertension secondary to correctable congenital heart disease (10%)

6. What are the most common indications for a double-lung transplant?

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* Cystic fibrosis (35%)
* Emphysema (20%)
* Alpha-1 antitrypsin deficiency (11%)
* Primary pulmonary hypertension and pulmonary hypertension secondary to correctable congenital heart disease (20%)
* Idiopathic pulmonary fibrosis (8%)

7. What are the most common indications for heart-lung transplant?

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Primary pulmonary hypertension (30%) and cystic fibrosis (16%) are instances in which bad lungs have ruined a good heart. Conversely, with congenital heart disease (27%), a bad heart has destroyed good lungs.

8. What is sewn to what during a single-lung transplant? A double-lung transplant?

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During a single-lung transplant, recipient-to-graft bronchial, pulmonary artery, and pulmonary vein (atrial cuff) anastomoses are required. Anastomoses for double transplant are the same; however, cardiopulmonary bypass is required more often during double-lung transplant. During implantation of the second lung, diversion of the entire cardiac output to the freshly ischemic lung often results in reperfusion lung edema and hypoxemia.

9. Which diagnoses carry the best results for single-lung transplants?

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Patients with emphysema and alpha-1 antitrypsin deficiency do significantly better, with 1-year survival rates of 80%.

10. Why is the number of combined heart-lung transplants performed annually decreasing?

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Approximately 250 heart-lung transplants were performed in 1990; the number has decreased to approximately 150 in 1999. As the results of single- and double-lung transplants have improved, the need to perform heart-lung transplants in patients with isolated pulmonary disease has been obviated.

11. What are the most common complications after lung transplant?

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* Airway surgical healing defects (early)
* Rejection (early)
* Bacterial and cytomegalovirus infections (weeks to months)
* Bronchiolitis obliterans (months to years)

12. What is bronchiolitis obliterans?

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Bronchiolitis obliterans, a major cause of long-term morbidity after lung transplantation, is a process in which membranous and respiratory bronchioles demonstrate histologic evidence of subepithelial scarring that eventually progresses to occlusion of the bronchiolar lumen. Clinically, it is characterized by dyspnea and airflow obstruction.

13. What are the risk factors for the development of bronchiolitis obliterans after lung transplant?

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Donor age > 40 years and donor ischemic times > 6 hours.

14. How is lung transplant rejection diagnosed?

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Unlike heart transplants, the diagnosis of rejection in transplanted lungs is imprecise and based on a collection of symptoms and signs. Decreased oxygen saturation, fever, decreased exercise tolerance, and radiologic infiltrate suggest rejection. Sequential quantitative lung perfusion scans that demonstrate a decrease in perfusion are helpful in the diagnosis of rejection after single-lung transplants. Transbronchial biopsy is useful after single- and double-lung transplants.

15. Describe the phenomenon of chimerism in transplantation.

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Chimerism is leukocyte sharing between the graft and the recipient so that the graft becomes a genetic composite of both the donor and recipient. Chimerism enhances the host’s tolerance of the graft because the recipient does not recognize the donor organ as foreign. The first evidence of chimerism was observed in 1969 when female recipients of male livers developed entirely female Kupffer cell (liver macrophage) systems (as demonstrated by the Barr bodies in the macrophage). In 1992, the concept of immune cell sharing became clinically evident when it was discovered that leukocytes from donor kidneys occupied remote lymph nodes.

16. Do resident macrophages exist in the heart and lungs?

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Absolutely yes. Resident myocardial macrophages and resident alveolar macrophages are incredibly active cellular components of the heart and lungs.

17. Does chimerism develop in the heart and the lungs?

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Yes. Because the heart and lungs each have leukocytes to share, they participate in chimerism.

18. Why is chimerism exciting?

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Nature is trying to teach us how to perform transplantation without the use of immunosuppression. Our job is to learn why chimerism is induced in some recipients and not in others. That is, we should dissect the mechanisms of chimerism induction so that we may therapeutically induce chimerism in all recipients.

19. What are the major types of preservation solutions for heart and lung grafts?

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Euro-Collins (EC) solution and University of Wisconsin (UW) solution for lung and crystalloid cardioplegia and UW solution for hearts.

20. What percentage of pulmonary blood flow goes to the transplanted lung after single-lung transplant?

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Predictably, almost all of the pulmonary blood flow passes through the lower resistance circuit of the transplanted lung (depending on the pulmonary vascular resistance of the contralateral native-i.e., sick-lung). If a preoperative perfusion scan exists, other factors being equal, the lung with the best perfusion is preserved and the bad lung is replaced.
KEY POINTS: LUNG TRANSPLANTATION

1. The most common indication for single lung transplant is emphysema.
2. The most common indication for double lung transplant is cystic fibrosis.
3. Chimerism is leukocyte sharing between the graft and the recipient so that the graft becomes a genetic composite of both donor and recipient.
4. Bronchiolitis obliterans, a major cause of long-term morbidity after lung transplantation, is a process in which membranous and respiratory bronchioles demonstrate histologic evidence of subepithelial scarring that eventually progresses to occlusion of the bronchiolar lumen.

21. Is cardiopulmonary bypass required for lung transplantation?

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No. However, for patients with pulmonary hypertension (primary or secondary), cardiopulmonary bypass is routinely used before removal of the recipient’s lung. Cardiopulmonary bypass is always on standby. This is tricky anesthesia. One lung is transiently excised from a patient who is living (barely) on two bad lungs.

22. Is living-related lung transplant possible?

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Yes. Living-related lung transplants are an innovative approach to increasing the donor pool. Typically, only one lobe from the donor is used to replace a whole lung in the recipient.

23. What is lung volume reduction surgery? How may it be important to patients on the lung transplant waiting list?

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Lung volume reduction surgery offers a therapeutic option for patients who are either not candidates to receive a lung transplant or on a long waiting list. Lung volume reduction surgery removes nonfunctional or destroyed lung. Removal of defunctionalized lung makes more room for airflow in the functional lung, thereby decompressing the distended chest.

24. Who is the best candidate for lung volume reduction surgery?

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The best candidates are patients without contraindication who have absent or reduced perfusion of approximately one third of the lung (usually caused by a big cyst or emphysematous region), with good flow distribution in the remainder of the lung. Thus, quantitative lung perfusion scans provide essential information for patient selection.

25. What are the contraindications to lung reduction surgery?

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* Pulmonary hypertension (mean pulmonary artery pressure [PAP] > 35 mmHg or systolic PAP > 45 mmHg)
* Significant coronary artery disease
* Previous thoracotomy or pleurodesis (visceral and parietal pleural fusion)
* Long-standing history of asthma, bronchiectasis, or chronic bronchitis with purulent sputum
* Severe kyphoscoliosis

26. What is the most common nonbacterial cause of pneumonia in lung transplant patients?

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Cytomegalovirus (CMV), usually occurring 4-8 weeks postoperatively. Primary CMV infection usually results in more serious illness than reactivation disease. CMV-seronegative recipients should receive only blood products that are serologically negative.

27. In addition to immune suppressive therapy, what other factors put transplanted lungs at risk for infection?

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Lung denervation, interruption of lymphatic clearance and bronchial circulation, and impaired mucociliary clearance.

28. What are the main differences in composition between EC and UW solutions?

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EC solution is a glucose-based solution with an ionic composition that approximates that of the intracellular environment.
UW solution does not contain glucose but does contain the following components not found in EC solution: hydroxy-ethyl starch (prevents expansion of the interstitial space), lactobionate and raffinose (suppress hypothermia-induced cell swelling), glutathione and allopurinol (reduce cytotoxic injury from oxygen free radicals), and adenosine (substrate for adenosine triphosphate formation, vasodilation, and activation of the protective mechanisms of “protective preconditioning”).

29. How many lung transplants are performed annually? Is the number increasing or decreasing?

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Of interest, although the first human lung transplant was performed in 1963, significant numbers were not performed until the late 1980s (in 1986, 1 lung transplant; in 1989, 132 lung transplants). This number rapidly increased to 700 per year in 1994 and has since declined to approximately 625 per year worldwide.

30. Are the survival rates different for single- and double-lung transplants?

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No. The 3-year actuarial survival rate is about 50% for each.

31. What are the 1-year, 2-year, and 3-year actuarial survival rates for single-lung retransplants?

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Actuarial survival rates are 45%, 40%, and 30%, respectively. Predictably, such patients do significantly worse.

References
WEB SITE
http://www.transplantation-soc.org
BIBLIOGRAPHY
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