Lung Transplant: Candidates for Referral and the Waiting List

By Kenneth R. McCurry, MD, and Marie M. Budev, DO, MPH

Identifying patients who are appropriate candidates for lung transplant is important to achieving favorable transplant outcomes and to maximizing life expectancy for each patient. The most recent edition of International Society for Heart and Lung Transplant (ISHLT) Guidelines for the Selection of Lung Transplant Candidates is an excellent guide to help physicians identify when to refer potential patients and to how to identify patients who are the most likely to benefit from lung transplant.

Adults with end-stage lung disease are generally candidates for lung transplant if they meet the following criteria:

• A greater than 50 percent risk of death from lung disease within two years if a lung transplant is not performed
• A greater than 80 percent likelihood of surviving at least 90 days after the lung transplant procedure
• A greater than 80 percent likelihood of a five-year survival posttransplant if graft function is preserved.

These can only be estimated by transplant programs and not by the referring team in most cases.

Once a patient is identified as a candidate for lung transplant, early referral of patients to a lung transplant program has several advantages and is essential for positive outcomes. Early patient referral allows for timely completion of the formal evaluation of candidacy, patient and family education, as well as the opportunity for the patient and family to raise funds or use other resources to overcome financial hurdles.

Noncandidates for lung transplant

Generally, most transplant centers in the United States agree that contraindications to lung transplant include conditions associated with increased risk of mortality, including:

• A recent history of a major malignancy.
• The presence of significant dysfunction of another major organ systems including the heart, liver, kidney or brain unless a combined organ transplant can be considered and performed.
• Significant coronary heart disease not amenable to revascularization or intervention prior to or at the time of lung transplant.
• The presence of an acute medical condition including but not limited to sepsis and acute liver failure.
• Active Mycobacterium tuberculosis and other highly virulent or highly resistant microbes that are poorly controlled pretransplant.
• Severe obesity with a body mass index greater than 35.
• A history of nonadherence to medical therapy, psychiatric or psychological conditions that might lead to nonadherence, poor or limited social support system and limited functional status not amenable to rehabilitation.
• Current substance abuse or dependence, including illicit substances, alcohol and tobacco (nicotine-containing substances). Most centers require at least six months’ abstinence from illicit substances prior to being added to the lung transplant waitlist.

Candidate comorbidities

Age

Many transplant centers in the U.S. define the age cutoff for lung transplant at 65; however, some centers may consider candidates older than 65. Advanced age by itself should not be considered a contraindication to lung transplant. However, increased age is usually associated with other comorbid conditions that may increase perioperative and long-term morbidity and mortality.

Past chest surgery

It is not uncommon for lung transplant candidates to have a history of chest surgery such as lung resection, pleurodesis or coronary artery bypass grafting. The limited literature regarding the outcomes for these patients suggests they may experience higher rates of bleeding, re-exploration and renal dysfunction. However, these patients should not be excluded from lung transplant and successful transplant outcomes have been achieved in this population by experienced centers. In candidates with a history of chronic obstructive pulmonary disease (COPD) and lung-volume reduction surgery (LVRS), early case series indicate that these patients did well after lung transplant. However, more recent data demonstrate that patients with prior LVRS who undergo lung transplant experience higher rates of bleeding, worse early graft dysfunction and worse outcomes overall. As with lung transplant candidates with previous chest surgery, lung transplant candidates with previous LVRS are best served by experienced transplant centers.

Hepatitis and HIV

Patients with a history of infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV) are candidates for lung transplant at centers experienced with lung transplant in patients with these infections. Most centers advocate that patients with a history of hepatitis B or C have viral infection levels that are controlled or reduced as low as possible and that there is no evidence of portal hypertension or severe cirrhosis. In the case of HIV, patients should have controlled disease with a negative or undetectable viral load and have no current acquired immunodeficiency defining illness.

Disease-specific indications

Chronic obstructive pulmonary disease

Patients with COPD should be referred for lung transplant if the body mass index, airflow obstruction, dyspnea and exercise capacity (BODE) index is 5 to 6.2. Other considerations for referral for lung transplant include the presence of hypercapnia with partial pressure of carbon dioxide greater than 50 mm Hg or higher or hypoxemia with partial pressure of oxygen less than 60 mm Hg or a forced expiratory volume at 1 sec (FEV1) less than 25 percent predicted.

Patients with COPD should be considered for listing for lung transplant if any one of the following criteria is met: BODE index of 7 or greater; FEV1 less than 15 to 20 percent; three or more severe exacerbations during the preceding year; one severe exacerbation with acute hypercapnic respiratory failure; or presence of moderate to severe pulmonary hypertension.

Cystic fibrosis

In patients with cystic fibrosis, lung transplant should be considered in patients with an estimated two-year survival of less than 50 percent and with a New York Heart Association (NYHA) Functional Classification III or IV. Referral for lung transplant is recommended for patients with a rapid decrease in FEV1 despite optimal therapy, female patients with declining weight and lung function, colonization or infection with nontuberculous mycobacterial disease or cystic fibrosis-related diabetes. The development of pulmonary hypertension, reduction in walk distance, increasing antibiotic resistance, acute respiratory failure requiring noninvasive ventilation, worsening nutritional status, pneumothorax and life-threatening hemoptysis despite embolization are all indications for referral for lung transplant.

Patients with cystic fibrosis with hypoxia or hypercapnia with declining lung function, needing long-term noninvasive ventilation, having more frequent exacerbations or exhibiting a decline in functional status should be listed for lung transplant.

Restrictive lung disease

Patients with restrictive lung diseases, including interstitial pulmonary fibrosis (usual interstitial pneumonitis, nonspecific interstitial pneumonia), or interstitial lung disease, and hypersensitivity pneumonitis, should be referred for transplant evaluation at the time of diagnosis irrespective of lung function due to the unpredictable nature of these diseases. Some clinicians may advocate for a trial of medical therapy with antifibrotics, but this should be done in conjunction with transplant referral.

Patients should be listed for transplant if a 10 percent or greater decrease in FEV1 occurred in the past six months (of note, even a 5 percent decrease in FEV1 is associated with an overall poorer prognosis and warrants consideration of listing for transplant), if the diffusing capacity of the lung for carbon monoxide decreases 15 percent or greater during the six-month follow-up, or if a decline of more than 50 meters is noted on the six-minute walking test. A documented desaturation of less than 88 percent or a distance of less than 250 meters on the six-minute walking test is another indication for listing. Any evidence of secondary pulmonary hypertension on right heart catheterization or on echocardiography or hospitalization for respiratory decline are also indications for listing. In cases of scleroderma-associated interstitial lung disease or mixed connective tissue interstitial lung disease, similar guidelines for referral and listing should be followed.

Pulmonary arterial hypertension

Patients with pulmonary arterial hypertension should be referred for lung transplant if any one of the following conditions is present: rapidly progressive disease; NYHA Functional Classification III or IV symptoms during escalating therapy; use of parenteral pulmonary arterial hypertension therapy; or known or suspected pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis.

Patients with pulmonary arterial hypertension should be listed for lung transplant if any of the following are present: NYHA Functional Classification III or IV symptoms despite combination therapy; right heart catheterization demonstrating a cardiac index less than 2 L/min/m2; mean right atrial pressure greater than 15 mm Hg; six-minute walking test less than 350 meters; or development of pericardial effusion, hemoptysis or signs of worsening right heart failure, including renal insufficiency, rising bilirubin or evidence of ascites.

Conclusion

To ensure good patient outcomes, the evaluation and selection of candidates for lung transplant requires communication between referring physicians and lung transplant centers. An open, two-way dialogue between referring providers and transplant centers facilitates listing patients for transplant in a timely manner, reduces delays and improves outcomes.

Dr. McCurry is a cardiothoracic surgeon in the Sydell and Arnold Miller Family Heart & Vascular Institute at Cleveland Clinic. Dr. Budev is the Macon and Joan Brock Endowed Chair for Lung Transplantation.

This abridged article was originally published in Cleveland Clinic Journal of Medicine.