When Is Lung Transplantation an Option in COPD?

By Shruti Gadre, MD

Patients with chronic obstructive pulmonary disease (COPD) are one of the largest cohorts referred for lung transplantation. However, the criteria for referral and the indications for transplant aren’t always clear.

Regardless, early referral to a transplant center is always beneficial, even if the patient is not yet deemed to be a transplant candidate.

COPD versus other end-stage lung diseases

COPD is the third leading cause of death globally and remains the most common reason for lung transplantation worldwide. Patients with COPD and alpha-1 antitrypsin deficiency (AATD) accounted for 34.7% of all lung transplants performed between 1995 and 2018, according to an International Thoracic Organ Transplant Registry report.

It is important to note several key differences between COPD and other end-stage lung diseases that merit referral for lung transplant. Patients with COPD:

• Experience a loss in lung function over a longer period of time. It can become difficult to determine when in the course of the disease patients should be referred or listed for transplant. The long natural history means that these patients have the potential for more deconditioning. Waiting too long to transplant allows for progression of debility.
• Have less short-term mortality. Even in advanced stages of COPD, short- and intermediate-term survival is better than in other diseases for which lung transplant is performed. Because mortality in COPD is seen beyond one year, patients with COPD receive a lower lung allocation score (LAS), are prioritized lower on the transplant waitlist and thus have longer wait times.
• Experience a progressive decline in quality of life. There is debate on whether the quality of life should be considered when making decisions about lung transplantation. Currently, the LAS does not factor in a quality-of-life benefit. Therefore, patients with COPD may be disadvantaged.
• Have a longer lung transplant window. The window for lung transplantation is the period of time when the disease is advanced enough for the patient to benefit from a transplant, but not too ill to undergo the operation. When a patient is in the window, the benefits of transplant outweigh the risks, and the patient should be listed for transplantation. It is best to refer a patient earlier in the transplant window or before it. An early referral allows the transplant pulmonologist and referring physician time to collaborate and optimize the patient for transplant by enrolling them in pulmonary rehabilitation, weaning maintenance systemic steroids, evaluating and treating obstructive sleep apnea, and working on weight loss.

Determining survival benefit

The median survival after lung transplantation is 6.7 years. Even for patients with advanced COPD, this time may be shorter than the expected survival without transplant. Because of the slow progression of COPD, a survival benefit from transplant is not always easy to discern.

To identify patients most likely to benefit from transplant, we must consider:

• Predicted mortality. Low forced expiratory volume in one second (FEV1) is the most common reason for referral to a lung transplant center, but by itself it is insufficient to determine benefit from transplantation. The BODE index — which combines body mass index (BMI), FEV1, Modified Medical Research Council dyspnea score and six-minute walk distance (6MWD) into weighted scores on a 10-point scale — has proven to be a better indicator of survival than the spirometric staging system alone. A BODE score of 7-10 is associated with a mortality of 80% at four years; a score of 5-6 is associated with a mortality of 60% at four years. Thus, patients with a BODE score of 7 or higher may be appropriate to transplant.
• Predicted survival after lung transplant. Further complicating patient selection, several factors that predict higher mortality in COPD also are associated with poor outcomes after transplant. For example, physical deconditioning can lead to reduced 6MWD and predispose the patient to worse outcomes after transplant. Low BMI and older age are associated with shorter survival after transplant. Pulmonary hypertension increases the relative risk of mortality at one year after transplant in patients with COPD compared to patients with idiopathic pulmonary fibrosis or cystic fibrosis.
• Quality of life. Literature on the impact of lung transplant on quality of life for patients with COPD is limited. However, a 2011 study reported that patients with a BODE score of 5-6 had similar improvements in quality of life after transplant as patients with a BODE score of 7-10, indicating that transplant can improve quality of life even when not expected to have a mortality benefit.

Therefore, it is challenging to identify patients with advanced COPD who will achieve both a survival and quality-of-life benefit from a lung transplant. Determining a patient’s suitability for transplant is a complex decision made by engaging the expertise of multidisciplinary teams and considering the best available data. Decisions are made on a case-by-case basis, but patients typically are listed for transplant when they meet at least one of the following criteria:

• BODE index ≥7
• FEV1<15% to 20% predicted
• Three or more severe exacerbations during the preceding year
• One severe exacerbation with acute hypercapneic respiratory failure
• Moderate to severe pulmonary hypertension

Management strategies for patients without survival benefit

When a patient doesn’t (or doesn’t yet) qualify to be listed for transplant, there are several management strategies to consider:

• Refer to a transplant center and follow. Patients may eventually progress into the transplant window.
• Pulmonary rehabilitation. This provides well-established benefits in COPD for dyspnea, exercise capacity and health-related quality of life. Pulmonary rehabilitation is also required for lung transplant candidates. Patients unable to participate are unlikely to be candidates for transplant.
• Lung volume reduction (surgical or endobronchial). Some patients may be candidates for this procedure, either instead of or as a precursor to lung transplant. Successful lung volume reduction, and the associated improvement in functional and nutritional status, can improve a patient’s suitability for transplant.

Previous cardiothoracic surgery and endoscopic or surgical lung-volume reduction are not contraindications to lung transplantation.

In summary, not all patients with COPD will derive a mortality benefit from transplant. Identifying those who are likely to benefit can be challenging. Management strategies are available for patients who do not yet but may ultimately have a survival benefit. Early referral to a transplant center is beneficial because it allows the opportunity to optimize a patient’s condition to make them the best possible candidate for lung transplant.

About the author: Dr. Gadre is a lung transplant physician and critical care specialist in Cleveland Clinic’s Respiratory Institute. This article is based on her presentation “COPD: When and Whom to Refer for Lung Transplantation?” at the 2020 CHEST® Annual Meeting.