What is FPF?

What is familial pulmonary fibrosis?

When two or more members of the same family have idiopathic pulmonary fibrosis (IPF) or any other form of fibrotic interstitial lung disease it is considered familial pulmonary fibrosis (FPF). Typically, FPF appears in immediate family members (parent, child or sibling). It also can be second degree family members such as aunts, uncles and cousins.

In about half of families with familial pulmonary fibrosis, not all affected members have the same type of interstitial lung disease. One or more family members may have IPF (the most common fibrotic interstitial lung disease) and another may have a different form of ILD.

Possible types of fibrotic interstitial lung diseases in families include:

• Chronic hypersensitivity pneumonitis 
• Connective tissue disease interstitial lung disease (CTD-ILD)
• Non-specific interstitial pneumonia (NSIP)
• Unclassifiable interstitial lung disease (U-ILD)

Genetic Causes of Familial Pulmonary Fibrosis

It is estimated that 1 in 5 people with pulmonary fibrosis or fibrotic interstitial lung disease have familial pulmonary fibrosis.  In about one third of these cases, a genetic variant that causes the disease can be identified using commercially available genetic tests.  

The most common gene mutations associated with FPF affect biologic pathways related to telomeres and surfactant.  Telomeres are specialized caps at the end of chromosomes.  These caps are important because they protect the chromosome’s physical structure from breakdown or “shortening”.  A number of genes are responsible for ensuring that telomeres function properly. Harmful variants in several of the telomere genes have been identified in FPF.

Another biologic pathway associated with FPF impacts lung surfactant. Surfactant is a substance produced inside lung air sacs so they can expand and contract easily. Harmful surfactant variants are associated with FPF.  Surfactant variants are slightly less common than telomere mutations in FPF.  Together, however, these types of mutations make up nearly all of these known, testable genetic variants of FPF.

Signs and Symptoms

Pulmonary fibrosis is ongoing scarring in the lungs, which makes it more difficult to breathe over time. Individuals with the familial form of IPF or other types of ILD are likely to experience symptoms that include:

• Breathlessness
• Dry cough
• Fatigue

Diagnosis

Familial pulmonary fibrosis is essentially the same disease as fibrotic interstitial lung disease that is not familial (i.e., sporadic). In FPF, typically at least one family member carries the diagnosis of idiopathic pulmonary fibrosis.

Genetic Testing & Counseling

When a parent has a harmful variant in a gene related to familial pulmonary fibrosis, each child has a 50% chance of inheriting the variant. Children who inherit the disease variant may not necessarily develop FPF, but they have an increased risk compared to people without the variant. Different families with FPF have different gene variants. It’s helpful to know which specific genetic variant is present to streamline genetic testing for other family members. Testing for a known variant in a specific gene is easier than someone’s full set of 22,000 genes.

Genetic testing for FPF is typically conducted through a blood or saliva sample. This testing is recommended for people who have been diagnosed with familial pulmonary fibrosis, rather than unaffected family members. Not every genetic variant responsible for FPF is known, so negative results do not necessarily rule out an inherited risk. Possible genetic screening can be discussed with your healthcare provider.

Genetic counseling is the process of providing individuals and families with information on the inherited risk and implications of genetic disorders to make informed medical and personal decisions. A qualified genetic counselor can help you understand your risk for pulmonary fibrosis, the risk to other members of your family and answer any questions you may have.

Genetic testing for pulmonary fibrosis is often complex. The results may be difficult to interpret on your own. It is important to discuss the implications of the test with a genetic counselor before and after the test. A genetic counselor can help you determine if other family members should consider DNA testing.

Genetic testing is not recommended for people with non-familial pulmonary fibrosis. These are called “sporadic” cases, and they account for the vast majority of fibrotic ILDs. In these patients, genetic testing does not provide meaningful results.  

Treatment

Patients with FPF typically have the same treatment options as people with non-familial forms of the disease. While there is no cure for pulmonary fibrosis, there are treatments that slow down disease progression. An accurate diagnosis and comprehensive treatment plan are necessary in order to have the best outcomes.

Clinical Trials

Clinical trials help determine new treatment options for diseases and conditions. While there are no specific trials addressing familial pulmonary fibrosis, patients have access to clinical trials for other types of interstitial lung disease. Patients should speak with their doctor to determine what trials might work best for them.