Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients.

Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in premature shortening of telomeres, the caps on the ends of cellular DNA that protect chromosome length during cell division, leading to early cell senescence and death. Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of the telomere biology disorders, although it has been described in other interstitial lung diseases as well, such as rheumatoid arthritis-associated ILD and chronic hypersensitivity pneumonitis. Telomere-related mutations can be inherited or can occur sporadically. Identifying these patients and offering genetic counseling is important because telomerapathies have been associated with poorer outcomes including death, lung transplantation, hospitalization, and FVC decline. Additionally, treatment with immunosuppressants has been shown to be associated with worse outcomes. Currently, there is no specific treatment for TBD except to transplant the organ that is failing, although there are a number of promising treatment strategies currently under investigation. Shortened telomere length is routinely discovered in patients undergoing lung transplantation for IPF. Testing to detect early TBD in patients with suggestive signs or symptoms can allow for more comprehensive treatment and multidisciplinary care pre- and post-transplant. Patients with TBD undergoing lung transplantation have been reported to have both pulmonary and extrapulmonary complications at a higher frequency than other lung transplant recipients, such as graft-specific complications, increased infections, and complications related to immunosuppressive therapy.