Pulmonary - Critical Care Associates
of East Texas

Jeffrey M. Shea, M.D., F.C.C.P.
                              Venkatesh Donty, M.D.

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   Lung transplantation offers an option for treatment for patients with an otherwise terminal disease. Since the first successful lung transplantation practically 20 years ago, this procedure has been widely accepted as an option for those with a wide array of lung diseases and limited life expectancy. The procedure is, however, associated with frequent complications.

    Despite the continued growth of the number of patients waiting for lung transplants, the number of donors has remained relatively fixed at a level insufficient to meet demand. These trends have led to a leveling off of the number of transplants performed, a doubling of the median waiting time to approximately 18 months, and an increase in the number of patients who die while waiting for a transplant.

    Along with the growth in the transplantation field has been an expansion of the number of diseases that transplantation is offered. Transplantation is an option for the following diseases:

• Chronic Obstructive Lung Disease (Accounts for about 45% of transplants)
• Cystic Fibrosis
• Idiopathic Pulmonary Fibrosis
• Primary Pulmonary Hypertension
• Eisenmenger's Syndrome

and less commonly

• Sarcoidosis
• Lymphangioleiomyomatosis
• Eosinophilic granuloma
• Drug-induced and radiation-induced pulmonary fibrosis
• Lung disease from underlying collagen vascular diseases

Disease Specific Guidelines for Referral for Lung Transplantation

• FEV1 < 25% of predicted after a bronchodilator
• Clinically significant lack of oxygen, elevated CO2 on blood gas analysis, or increased pulmonary artery pressure; rapid decline in lung function; or frequent severe attacks of COPD

• Symptomatic disease unresponsive to medical therapy
• Vital Capacity <60 - 70 % of predicted
• Evidence of resting or exercise-induced fall in oxygenation

• FEV1 < 30 % of predicted
• FEV1 > 30 % of predicted with rapidly declining lung function, frequent severe attacks, or progressive weight loss.
• Female sex and age of less than 18 years with FEV1 > 30 % of predicted (associated with a poorer prognosis and therefore earlier referral suggested)

The use of stringent selection criteria is essential in the identification of candidates for whom transplantation is most likely to be successful.

• Advanced obstructive, fibrotic, or pulmonary vascular disease with a high risk of death within 2 or 3 years
• Lack of success or availability of alternative therapies
• Severe functional limitation, but preserved ability to walk
• Age of 55 years or less for candidates for heart-lung transplantation; age of 60 years or less for candidates for bilateral lung transplantation, and age of 65 years or less for candidates for single-lung transplantation.

• Severe extra-pulmonary organ dysfunction, including kidney impairment with a creatinine clearance below 50 ml/min, liver dysfunction with bleeding tendencies or cirrhosis, and impaired heart function or severe coronary artery disease (consider heart-lung transplantation)
• Acute, critical illness
• Active cancer or recent history of cancer with substantial likelihood of recurrence (except for basal-cell and squamous cell carcinoma of the skin)
• Active extra-pulmonary infection (including infection with HIV, hepatitis B and C)
• Severe psychiatric illness, noncompliance with therapy, and drug or alcohol dependence
• Active or recent (preceding 3 to 6 months) cigarette smoking
• Severe malnutrition (< 70 % of ideal body weight) or marked obesity (> 130 % of ideal body weight)
• Inability to walk, with poor rehabilitation potential

• Chronic medical conditions that are poorly controlled or associated with target-organ damage (including osteoporosis, high blood pressure, diabetes, heart disease)
• Daily requirements for more that 20 mg of prednisone (or equivalent)
• Mechanical ventilation (excluding noninvasive ventilation)
• Extensive pleural thickening from prior thoracic surgery or infection
• Active collagen vascular disease
• Preoperative colonization of the airways with pan-resistant bacteria (in patients with cystic fibrosis)

Features that distinguish the allocation of lungs from the allocation of other solid organs:

• In contrast to the allocation of hearts and livers, lung allocation is based on waiting time without regard for severity of illness or medical urgency. The only exception is a 90-day credit granted at the time of listing to patients with idiopathic pulmonary fibrosis (due to the disproportionately high death rate in this group of patients during the waiting period for transplantation).
• The lung is the most fragile organ in a patient who is brain-dead and is subject to damage by excessive administration of fluid, aspiration, and ventilator-associated pneumonia as well as by extensive prior cigarette smoking.
• For this reason, less than 20 % of cadaveric donors have lungs suitable for harvest
• The lung can tolerate only a brief period of lack of oxygen, typically less than 6 hours. This limits the geographic distribution of lungs for transplant. Due to the time limits, donors and recipients are matched on the basis of major blood groups and size of the chest/lungs.

According to the registry of the International Society for Heart and Lung Transplantation, 1-year, 3-year, and 5-year actuarial survival after lung transplantation is 70.7, 54.8, and 42.6 %, respectively, with a median survival of 3.7 years. Survival rates for lung transplantation have improved only moderately over the past 10 years despite refinements in surgical technique and postoperative care. These rates lag considerably behind those for heart and liver transplantation, for which five-year survival approximates 70 %.

The death rate is highest in the year after transplantation, with infection and graft failure representing the leading causes of early death. Factors that portend a poorer prognosis include a pre-transplantation diagnosis of pulmonary hypertension, dependence on a ventilator, and age of more than 50 in the recipient or donor.

Lung transplantation has reached its current clinical plateau largely through refinements in the selection of patients, operative techniques, and postoperative care. Two major hurdles must be overcome: the supply of organs, and chronic rejection must be more effectively prevented.

Xeno-transplantation - the use of animal organs for transplantation in humans, offers a potential solution to the shortage of donor organs. Research has focused on the creation of genetically engineered animals, in which the proteins in the animal organ that can cause the body to reject it, are removed or suppressed.

New drugs that are being tested clinically may be more effective and less toxic than drugs currently being used to prevent rejection. Newer ways at which to allow the body to tolerate the transplanted lung are being investigated.

Source: NEJM April 8, 1999 vol 340,14 p1081-89

 

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