There is a growing body of clinical research investigating idiopathic pulmonary fibrosis and telomere biology – here we explore some reasons why ordering a telomere length test may provide useful insight when diagnosing or treating someone with idiopathic pulmonary fibrosis.  

What is idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (PF) is a complex disorder characterized by progressive and irreversible lung scarring that ultimately leads to respiratory failure. Between 2 and 20% of cases of IPF appear to be familial.

There are known associations between telomere length and IPF, and these can help to provide information on underlying genetic causes of the condition, disease progression and common co-morbidities or complications.

Individuals affected by telomere biology disorders (TBDs) are known to be at higher risk of IPF (along with bone marrow failure and certain types of cancer). Up to 10% of individuals with idiopathic PF have been found to also have short telomeres and mutations in the telomerase genes, TERC and TERT. Another important study found that approximately 7% of familial PF cases can be explained by mutations in PARN and RTEL1 (genes known to influence telomere length).

Why might it be helpful to order a telomere test for idiopathic pulmonary fibrosis?

1. As a useful addition to, or in combination with, genetic testing

With knowledge and evidence growing for the usefulness of both telomere length testing and genetic testing in IPF, there has been consideration for how these tests should be used in clinical practice.

Some teams conduct telomere length testing prior to genetic testing. It has been proposed that it can be a useful preliminary test, if the result shows short telomeres (<10th percentile) it would indicate that a genetic test could be useful. As the cost and turn around time of a telomere length test compares favorably to a genetic test, it could be considered a useful frontline option.

Conversely, there are those that would advocate running the tests concurrently, as they can provide results with independent clinical value, in some cases. Further consideration and recommendations would be useful to provide guidance on which IPF patients to test, how and when.

2. To support disease course prediction, treatment timing and assess possible co-morbidities

Associations have been found between shorter telomere length and poorer prognosis in IPF patients. Being able to predict the speed of progression of the condition can help physicians to make informed decisions around monitoring, treatment and transplant.

Telomere length measurements can also provide insight into potential risk for co-morbidities that may be present, or occur in future, alongside IPF. If telomeres are found to be critically short, the patient may be diagnosed with an isolated subtype TBD, and in time possibly a dyskeratosis congenita (DC) like diagnosis. Having a more complete picture of the patient’s condition provides insight into potential disease progression, and enables ongoing monitoring for co-morbidities.

In addition, telomere length can in some cases indicate a familial component. This in turn can enable family members to be counseled for potential disease risk (both PF and other related TBDs), and the existence of genetic anticipation. To learn more, read this guest blog from Katie, a genetic counselor.

3. To support risk assessment for lung transplantation

PF is the most common indication for lung transplantation. Once the scarring that occurs in PF has affected lung function beyond a certain stage, a transplant becomes the only treatment option.

Studies have demonstrated that short telomere length is independently associated with transplantation-free survival. There is also evidence for an association between short telomere length and mutations in certain telomere-related genes with worse transplant outcomes in PF lung transplant patients with current protocols. Thus, having an awareness of a patient’s telomere length can be important when weighing up risks associated with a lung transplant and in investigating where approaches to improve outcomes can be made for this patient subset.

Furthermore, knowledge of a patient’s telomere length can impact clinical decisions regarding post-transplant care, and immunosuppression. PF patients with telomerase gene mutations have been seen to experience complications post-transplant related to their underlying TBD. In particular, hematologic complications including the risk of bone marrow failure, and the management of post lung transplant immunosuppression regimen, should be considered. Short telomere length can be considered a biomarker that can help to identify patients with IPF at risk for poor outcomes when exposed to immunosuppression. It has been suggested that telomere length testing should be considered as a component of the pre-transplantation evaluation for those patients with IPF.

Find out more about ordering a telomere length test with RepeatDx here.

Read more about telomere length testing for pulmonary fibrosis here.

Sources

Borie, R. et al. Severe hematologic complications after lung transplantation in patients with telomerase complex mutations. The Journal of Heart and Lung Transplantation. 2015 Apr; 34(4): 538-546. doi:10.1016/j.healun.2014.11.010.

Kannengiesser, C. et al. Pulmonary fibrosis: Genetic analysis of telomere-related genes, telomere length measurement-or both? Respirology. 2019; 24, 97–98. doi: 10.1111/resp.13456.

Kropski, J, A. et al. Genetic Evaluation and Testing of Patients and Families with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017 Jun 1; 195(11): 1423–1428. doi: 10.1164/rccm.201609-1820PP.

Newton, C, A. et al. Telomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine. 2018 Dec; 200(3). doi:10.1164/rccm.201809-1646OC.

Planas‐Cerezales, L. et al. Predictive factors and prognostic effect of telomere shortening in pulmonary fibrosis. Respirology. 2019 Feb;24(2):146-153. doi: 10.1111/resp.13423. Epub 2018 Oct 15.

Savage, S, A. and Bertuch, A, A. The Genetics and Clinical Manifestations of Telomere Biology Disorders. Genet Med. 2010 December; 12(12). doi:10.1097/GIM.0b013e3181f415b5.

Silhan, L, L. et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. European Respiratory Journal. Jul 2014, 44 (1) 178-187. doi: 10.1183/09031936.0006001.

Stuart, B, D. et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet. 2015;47(5):512‐517. doi:10.1038/ng.3278.

Swaminathan, A. et al. Lung Transplant Outcomes in Patients With Pulmonary Fibrosis With Telomere-Related Gene Variants. CHEST. 2019. doi:10.1016/j.chest.2019.03.030.