While we’ve learned so much about genetic diseases in recent years, there are still some conditions for which the cause is not fully understood. Among the many possible causes is genetics, and for patients with these conditions, genetics experts can play a key role in making sure they receive the right diagnosis and appropriate care. One example is pulmonary fibrosis (PF).

To understand the role of genetics in PF, it’s important to first understand the disease. PF is a serious, chronic disease that leads to lung scarring, making it progressively more difficult to breathe. Just as a scar can develop on the body following a serious cut or injury, with PF, the lung is injured and develops scars. There are more than 150 diseases that lead to PF, but when a cause cannot be identified it is known as “Idiopathic Pulmonary Fibrosis (IPF)”. The information below from the Pulmonary Fibrosis Foundation shows the types of PF and clues doctors use to diagnose the disease:

  • Drug-induced: Prior or current use of amiodarone, nitrofurantoin, chemotherapy, methotrexate, or other drugs known to affect the lungs
  • Radiation-induced: Prior or current radiation treatment to the chest
  • Environmental (called hypersensitivity pneumonitis): Exposure to mold, animals, or other triggers
  • Autoimmune (called connective tissue disease-related): Joint inflammation, skin changes (particularly on the fingers and face), dry eyes or mouth, abnormal blood tests
  • Occupational (called pneumoconiosis): Prior or current exposure to dusts, fibers, fumes or vapors that can cause PF (e.g., asbestos, coal, silica, and others)

PF can result from a number of causes:

  • Immunological disorder: Includes lupus, rheumatoid arthritis, sarcoidosis, and scleroderma, among others. Acid Reflux is also known to cause PF.
  • Exposure: Includes job-related and environmental toxins and pollutants, radiation treatments for cancer, certain medications, and viral and bacterial infections.
  • Genetics: Includes Familial PF (FPF), Hermansky-Pudlak syndrome (HPS), Dyskeratosis Congenita (DC), and other rare inherited disorders.
  • No known cause: The most common, Idiopathic PF (IPF) occurs spontaneously and has no known cause. There are different types of IPF, most of which do not have a known genetic component.

The average age of diagnosis of IPF is 65 and it is often accompanied by an average life expectancy of 1-5 years, however every patient will have his/her own outcome. While the only current cure is a lung transplant (not an option for most patients), two prescription drugs (Esbriet and Ofev) have been approved to slow disease progression.

An estimated 20% of patients with Idiopathic PF (IPF) have Familial PF (FPF) without a known inherited disorder. Research has identified several genes that are associated with FPF. However, these genes explain only about 20-25% of those with the familial form of IPF and even less for those with no family history (called Sporadic IPF).

Understanding of Familial PF (FPF) is continuing to grow. Early on, evidence showed that it was part of certain inherited disorders like Hermansky-Pudlak syndrome and Dyskeratosis Congenita (DC). But, in studying families, other genes have been found to have crossover with DC without the other classical features of DC. In addition, genes that play a role in homeostasis of the lungs, like surfactant proteins, have been associated with FPF. Evidence in mice models show differences when there is the same exposure(s) but different rates of developing FPF, so there appears to be some genetic predisposition to the disease. Categories of genes involved in FPF include telomere maintenance, surfactant, mucin, and others.

The are differences between Sporadic IPF and FPF from a genetics standpoint. The Familial PF patients have a greater concentration of rare, stronger effect genes (e.g. “Mendelian” inheritance -dominant, X-linked, recessive). The same genes represent a smaller percentage in Sporadic IPF (1-5%).

Idiopathic PF: Genetic-Allelic SpectrumIdiopathic pulmonary fibrosis

How genetic technology and discovery will change the way providers diagnose and treat Familial PF is still emerging. It isn’t routine to conduct genetic testing to diagnose the disease, but because of the 10-20% of people who have a family history, there’s a strong push to know which genes are in families. And as we’ve learned about more involved genes, genetics is becoming a brighter spotlight in these families. There is also growing interest in whether knowing genetic status can help with lung transplant post-care because of the way certain genes interact with other body systems. A promising development is that the Idiopathic PF medications being evaluated in clinical trials may incorporate more genetic components in the future.

Access to genetics expertise is beginning to change the way patients respond to a diagnosis of Familial PF (FPF). A diagnosis of FPF is not necessarily dire for siblings, children and grandchildren because of the mechanistic way in which PF is thought to run in families. In other words, even if the disease is inherited, it doesn’t mean that family members will get it, which gives patients some comfort.

Genetic testing is not yet widely accessible for Idiopathic PF (IPF) patients and results are complex and difficult for even most pulmonologists to interpret. This is why genetic counseling is so important before and after genetic testing. Even with the limitations that come with IPF, we are learning more about how certain genes are causing disease and can share that knowledge with patients and their families.

Genetic counselors can analyze family history for patterns, ensure the right tests are ordered, discuss treatment, mental and physical symptom management options, share information about clinical trials, identify potentially at-risk family members, and help patients consider unanticipated consequences such as genetic discrimination. Because of the deep complexity of Familial PF and related genetic testing, providers also benefit from the expertise of genetic counselors who specialize in this area.

Every day, I’m inspired by the dedication of the patients we serve to participate in research that is increasing our understanding of pulmonary fibrosis and will ultimately lead to better treatments and hopefully a cure.

Janet Talbert, M.S., CGC, is a senior genetic counselor at InformedDNA. She has worked in the Interstitial Lung Disease Program at National Jewish Health in a variety of capacities since 2003. She has also conducted extensive research with Familial PF patients, having served for 11 years as the clinical research coordinator for a genetic study for gene discovery. Janet is also an author on GeneReviews for this disease area and is an ambassador for the Pulmonary Fibrosis Foundation, also serving on its medical advisory board. She is a nationally renowned subject-matter expert in Familial PF and gives presentations to patient and support groups and physician groups nationwide, having co-chaired a soon-to-be-published position statement on genetic counseling and genetic testing for PF. Janet is investigating possibilities for developing a program where InformedDNA can work with the Pulmonary Fibrosis Foundation to improve the accessibility of genetic counseling and testing at clinical sites and care centers. In the meantime, patients can be referred by providers or may self-refer to InformedDNA if they would like genetic counseling for PF.
Janet spoke on this topic at the NSGC Annual Conference in November 2019, in an Educational Breakout Session entitled “Beyond Cystic Fibrosis: Pulmonary Genetic Disorders in Adulthood.”


To learn more about InformedDNA’s genetic counseling services, just submit the short form below; send us an email to healthsystems@InformedDNA.com; or, give us a call at 844-846-3763.


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