Lung transplant: Candidates for referral and the waiting list

DISEASE-SPECIFIC INDICATIONS

Chronic obstructive pulmonary disease

COPD (both non- and alpha-1 antitrypsin deficiency) is the most common indication for lung transplant and accounts for almost 32% of lung transplants worldwide.¹³ Patients should be referred for lung transplant when medical therapies, surgical interventions (ie, LVRS) and pulmonary rehabilitation have been maximized. In COPD, the loss of lung function occurs over a long period of time but patients are often more limited by diminished quality of life as lung function slowly declines.

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 The original BODE index developed by Celli et al,¹⁴ is a scoring system from 0 to 10 with a higher score indicating more severe disease and worse survival. A score of 5 to 6 indicates an estimated mortality of 60% at 4 yrs.^2,14,15 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% predicted.

Patients with COPD should 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%; 3 of more severe exacerbations during the preceding year; 1 severe exacerbation with acute hypercapnic respiratory failure; or presence of moderate to severe pulmonary hypertension.^2,16

Cystic fibrosis

In patients with cystic fibrosis, lung transplant should be considered in patients with an estimated 2-year survival of less than 50% 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.^2,17–19

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.²⁰ 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% or greater decrease in FEV₁ occurred in the past 6 months (of note, even a 5% 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% or greater during the 6-month follow-up, or if a decline of more than 50 meters is noted on the 6-minute walking test. A documented desaturation of less than 88% or a distance of less than 250 meters on the 6-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.²¹ In cases of scleroderma-associated interstitial lung disease or mixed connective tissue interstitial lung disease, similar guidelines for referral and listing should be followed.²

Pulmonary arterial hypertension

Patients with pulmonary arterial hypertension should be referred for lung transplant if any 1 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.^2,22

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; 6-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.^2,22

BRIDGE TO TRANSPLANT

Acute respiratory decompensation may occur in some candidates for lung transplant prior to listing for transplant or while on the transplant waitlist. In patients with failure of a single lung, a bridge to transplant may be necessary until a suitable organ is available. Mechanical ventilation and extracorporeal life support (ECLS) are 2 bridge strategies for lung transplant candidates. Mechanical ventilation is the most common lung transplant bridge strategy but it is less than ideal because it can lead to deconditioning and ventilator-associated infections that can negatively impact a patient’s suitability for transplant.

ECLS techniques that allow spontaneous breathing and potentially ambulation, known as awake or ambulatory ECLS, is a popular bridge therapy. Ambulatory ECLS is used as an alternative to mechanical ventilation to avoid the complications of mechanical ventilation and allow patients to avoid sedation and participate in rehabilitation.²³ Irrespective of the therapy used as a bridge to transplant, patients considered for a bridge are optimally evaluated from a medical and psychosocial perspective prior to bridge therapy.

Both bridge therapies increase the risk of infection, bleeding, and neurologic events; thus, patients need to be assessed repeatedly for these risks to determine ongoing suitability for lung transplant. It is important to note that delayed referral of patients with advanced disease or patients in an acute exacerbation negatively impacts the evaluation for lung transplant, placement on the lung transplant waitlist, outcomes, and suitability for bridge transplant strategies.

CONCLUSION

To ensure good patient outcomes, the evaluation and selection of candidates for lung transplant requires communication between referring physicians and lung transplant centers. Physicians need basic knowledge of patient conditions appropriate for lung transplant and direct communication with lung transplant centers. The workup, required testing, and timing of listing for lung transplant varies among transplant centers across the country, making communication between the referring providers and transplant centers crucial to good patient care. An open, 2-way dialogue between referring providers and transplant centers facilitates listing patients for transplant in a timely manner, reduces delays, and improves outcomes.