WASHINGTON, D.C.—Rheumatologists often have questions about if and when to refer their patients with systemic autoimmune rheumatic disease-related interstitial lung disease (SARD-ILD) for lung transplantation. At a session of ACR Convergence 2024, Sonye Danoff, MD, PhD, assistant professor in the Division of Pulmonary and Critical Care Medicine and co-director of the Hopkins Interstitial Lung Disease Clinic, Johns Hopkins Medicine, Baltimore, explored these and related issues.
Sonye Danoff, MD, PhD
Realistic Expectations for Lung Transplant
For patients with poor response to therapy and radically reduced expected life span from severe SARD-ILD, lung transplantation represents an important treatment option. But lung transplants are incredibly rigorous procedures with many potential short-term and long-term complications, with poorer median long-term survival compared with other types of transplants. Many patients with SARD-ILD who are considering transplant have additional disease factors that only add to these risks.
Dr. Danoff underscored the intensity and complexity of the surgery, which often takes 8–12 hours of operating time to complete.1 “It’s really important to have a realistic understanding of the likelihood of benefit for our patients, because clearly our goal is to provide the best for them,” she said.
By learning more about the procedure, rheumatologists may be in a better position to field questions from patients about when and if they might explore transplantation as an option.
SARD-ILD patients who are lung transplant candidates also need their underlying SARD under good medical control prior to transplant.
Contraindications
Dr. Danoff discussed some of the absolute contraindications for the procedure. These include recent history of malignancy, significant dysfunction of another organ system refractory to therapy (e.g., the heart or liver), severe atherosclerotic disease, uncontrolled bleeding disorder, chronic infection with highly virulent pathogens, chest wall deformity, medical instability (e.g., patients on ventilators), active substance abuse, poor compliance or body mass index (BMI) of 35 kg/m2 or higher, although the latter may be more flexible. Dr. Danoff noted that a BMI under 16 kg/m2 is also contraindicated, which can sometimes pertain to patients who have lost weight due to SARD-ILD medications.2
Relative contraindications can include such features as class I obesity (BMI ≥30 kg/m2 and ≤35kg/m2), severe malnutrition, severe osteoporosis and prior extensive lung surgery. Age over 65 is also a relative contraindication, although Dr. Danoff noted the field is moving more toward a model of physiologic age and overall fitness instead of chronological age.2
Certain systemic manifestations of SARDs can also increase risks and serve as relative or absolute contraindications. For example, a myositis patient with active muscle disease may be a poor candidate, as they are unlikely to recover well after surgery. Severe esophageal dysmotility, pulmonary hypertension or bone marrow involvement might be contraindications. Scleroderma renal crisis or other renal impairment can also increase risk, as might upper airway involvement from rheumatoid arthritis.3
Dr. Danoff also noted that some SARD-ILD patients have severe physical deconditioning related to their diseases, which can make recovery from the procedure more difficult.
SARD-ILD patients who are lung transplant candidates also need their underlying SARD under good medical control prior to transplant.
Referral Timing
Generally, patient referral for potential lung transplant should begin before the patient is in urgent need, before they meet criteria for active placement on the transplant list. This may allow time to address certain modifiable risk factors, such as obesity, malnutrition or medical comorbidities.4
Dr. Danoff noted some of the factors that indicate a patient may be ready for lung transplant referral, for example, lung imaging patterns suggestive of fibrosis. These tend to be patients with a usual interstitial pneumonia or nonspecific interstitial pneumonia pattern of ILD. Another factor is a forced vital capacity (FVC) of <40% predicted.5
“In addition to declines in lung function, the other thing that I think is a really important marker is when patients suddenly require oxygen for the first time; that’s telling us that they really have come to a point where they’ve changed their trajectory,” said Dr. Danoff.
Officially adding the patient to the transplant list usually happens a little later, not immediately after transplant referral. Markers that a patient is moving toward needing a transplantation include a ≥10% decline in FVC or a ≥15% decline in diffusing capacity of the lungs for carbon monoxide over a six-month period. Other signs are dropping oxygen saturation percentages and repeated hospitalizations.5
Dr. Danoff recommended taking steps to help patients prepare for transplant when it becomes necessary. At the same time, she suggested working to optimize therapy for ILD to delay the need for lung transplantation for as long as possible. “Every year therapies become better for connective tissue disease (CTD)-ILD, and lung transplant gets better,” she added.
Outcomes
Transplants can fail due to initial primary graft dysfunction, acute rejection or chronic loss of the allograft, leading to lung deterioration and, ultimately, patient death. Dr. Danoff shared unpublished data from Johns Hopkins showing that patients with SARD-ILD seem to have a higher risk of developing primary graft dysfunction compared with patients with idiopathic pulmonary fibrosis, the standard comparator non-SARD-ILD; SARD-ILD patients also may have higher rates of vascular complications.
Dr. Danoff noted that in recent years, median survival times after lung transplant have not improved as much for ILD patients as they have for some other indications for lung transplant. A 2023 analysis from the International Society for Heart and Lung Transplantation showed that the median survival time after lung transplantation from all indications is around six years, but for SARD-ILD this may be closer to five.6,7
“In lung transplantation we have made strides in the right direction regarding survival, but only modest strides for patients with ILD. The lung is a very tough organ [to transplant],” Dr. Danoff added.
The Johns Hopkins data indicate that most of the SARD-ILD patients survived for at least three years post-transplant, but differences in survival rates among different specific SARDs appeared after that. SARD-ILD patients with myositis tended to do the worst, a finding that has been reflected in at least one other international study.8
“Lung transplant is clearly a last resort for our patients with advanced ILD-CTD,” said Dr. Danoff. “I don’t say this because I think that there’s no reason to transplant patients, but I think that we have to have a realistic understanding of what we’re offering.”
Ruth Jessen Hickman, MD, a graduate of the Indiana University School of Medicine, is a medical and science writer in Bloomington, Ind.
References
- Murala JS, Hanif HM, Peltz M, et al. Lung transplantation: How we do it. Indian J Thorac Cardiovasc Surg. 2021 Sep;37(Suppl 3):454–475.
- Weill D. Lung transplantation: Indications and contraindications. J Thorac Dis. 2018 Jul;10(7):4574–4587.
- Rajagopala S, Jindal A. Lung transplantation in connective tissue disease associated interstitial lung disease. Indian J Rheumatol. 2021 Dec;16:S101–S108.
- Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021 Nov;40(11):1349–1379.
- Zhang N, Liu S, Zhang Z. Lung transplantation: A viable option for connective tissue disease?Arthritis Care Res (Hoboken). 2023 Nov;75(11):2389–2398.
- Singh TP, Cherikh WS, Hsich E, et al. Graft survival in primary thoracic organ transplant recipients: A special report from the International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2023 Oct;42(10):1321–1333.
- Prieto-Peña D, Martínez-Meñaca A, Calderón-Goercke M, et al. Long-term survival of lung transplantation for interstitial lung disease associated with connective tissue diseases: A study of 26 cases from a referral centre. Clin Exp Rheumatol. 2020 Jul-Aug;38(4):615–620.
- Yang X, Wei D, Liu M, et al. Survival and outcomes after lung transplantation for connective tissue disease-associated interstitial lung diseases. Clin Rheumatol. 2021 Sep;40(9):3789–3795.
