Pulmonary fibrosis and telomere length analysis

idiopathic pulmonary fibrosis affects approximately 5 million people

Let’s take a look at pulmonary fibrosis, and some of the research that is furthering knowledge around the role telomere length analysis could play in guiding clinical decisions.

Idiopathic Pulmonary Fibrosis (IPF) is a rare disease affecting approximately 5 million people worldwide. The average age at presentation is 66 years old. It is also the most common disease indication for lung transplantation, and without a transplant the disease has a poor prognosis. In a world where we have a rapidly expanding (and aging) population, along with an organ donation shortage, we need to find ways to better understand diseases such as IPF, and their outcomes.

What role can telomere length analysis play?

Fortunately, a lot of research has recently been, and is still being, conducted on this topic.

We have seen studies demonstrating links between IPF and mutations in TERT, TERC, PARN, RTEL1, TINF2, NAF1, DKC1 – the telomere maintenance genes, indicating a risk factor relationship. It is important to note however, that short telomeres can occur even in cases where no known telomere maintenance gene mutations are seen, so it can be important to assess telomere length as part of patient screening, in addition to testing for gene mutations.

Findings suggest short leukocyte telomere length (LTL) is linked to worse transplant-free survival outcomes. These results indicate telomeres could have a role to play in disease course prediction, with low LTL indicating faster disease progression and shorter transplant-free survival. Such findings may guide a more rapid intervention, where possible, for IPF individuals discovered to have short telomeres.

In particular, LTL results may need to be considered for patients under 60 years old, as it has been found that the IPF patient group with the poorest prognosis is younger patients with shorter telomeres.

We have also seen that mutations in the telomere genes, TERT, RTEL1 and PARN, are associated with worse post-transplant outcomes among pulmonary fibrosis (PF) lung transplant recipients. Currently all PF transplants are handled similarly regardless of the underlying genetic cause or predisposition. However, more research is underway to determine how this telomere length information could be used clinically to guide tailored treatment decisions with the goal of improving transplant outcomes.

Other study results could also impact treatment decisions; research has found an association between IPF patients with low LTL and an increase in adverse events following immunosuppressant treatments. This suggests that telomere length could be used as a biomarker to identify patients who may not respond well to immunosuppression. As well as factoring into risk-benefit decisions regarding immunosuppressant usage, telomere length results could identify patients who require post-transplant hematologic evaluations.

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

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Molina-Molina, M. Telomere shortening behind the harm of immunosuppressive therapy in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine. 2019. doi:10.1164/rccm.201812-2330ED.
Newton, C.A. et al. Telomere Length and Genetic Variant Associations with Interstitial Lung Disease Progression and Survival. European Respiratory Journal. 2019. doi:10.1183/13993003.01641-2018.
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. doi:10.1164/rccm.201809-1646OC.  
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