Oct. 09, 2026
The field of interstitial lung disease (ILD) management continues to evolve. Mayo Clinic pulmonary medicine physicians are particularly excited about two advances: genetic diagnostics for familial pulmonary fibrosis and newer antifibrotic therapies.
Genetic evaluation is becoming increasingly important in treating familial pulmonary fibrosis (FPF), which can be driven by inherited genetic variants. Despite the name, FPF does not always present with an apparent family history.
Though increasingly recognized by the medical community, FPF awareness still lags. "These patients currently are inaccurately diagnosed with idiopathic pulmonary fibrosis, interstitial pneumonia with autoimmune features and other forms of ILD," says Eva M. Carmona Porquera, M.D., Ph.D., a pulmonologist specializing in ILD and director of the ILD and Familial Pulmonary Fibrosis Clinic at Mayo Clinic in Rochester, Minnesota.
Often, patients with FPF are appropriately treated with antifibrotics. But depending on the underlying genetic mutation, these patients may face risks beyond the lungs, particularly patients with telomere biology disorders and surfactant protein variants. These risks include but are not limited to lung cancer, liver disease and bone marrow failure.
"So, you don't just need to give these patients an antifibrotic," Dr. Carmona Porquera says. "You also need to tell them the risks of other possible comorbidities they may face."
To refine the diagnosis, Mayo Clinic pulmonologists refer selected patients to the Genetic Testing and Counseling (GTAC) Unit for telomere length and genetic testing when clinical features suggest inherited disease, including:
- A family history of pulmonary fibrosis.
- Clinical features suggestive of surfactant protein or telomere biology disorders.
- Early-onset fibrosis at age 60 or younger.
- Progressive fibrotic disease.
The telomere length evaluation uses flow cytometry with fluorescence in situ hybridization (FlowFISH). This CLIA-certified assay measures telomere length separately in lymphocytes and granulocytes from a blood sample. Doctors interpret results alongside genetic testing to provide a more complete clinical picture.
When testing reveals a hereditary form of pulmonary fibrosis, the implications extend beyond the individual patient. "The next question is what this means for the family," Dr Carmona Porquera says. "Do we need to facilitate family testing? Who may benefit from pulmonary assessment or earlier surveillance?"
A team that includes pulmonary and genetic counselors and genetic researchers guides patients on the next steps. These often include genetic testing for relatives and referring at-risk family members to specialists.
Dr. Carmona Porquera compares this approach to hereditary breast cancer screening, in which family history can prompt genetic evaluation and earlier surveillance. "We should think about familial pulmonary fibrosis in a similar way," she says. "Recognizing inherited risk gives us an opportunity to identify at-risk family members, monitor them appropriately and potentially detect disease earlier."
Choosing among antifibrotics amid evolving evidence
Until recently, pulmonologists primarily relied on two antifibrotic medications to slow the progression of pulmonary fibrosis: nintedanib and pirfenidone.
Nintedanib is a tyrosine kinase inhibitor. Pirfenidone's precise mechanism remains unclear.
In October 2025, the U.S. Food and Drug Administration (FDA) approved nerandomilast for idiopathic pulmonary fibrosis (IPF). The FDA extended approval to progressive pulmonary fibrosis (PPF) in December 2025.
The FDA based its approval on the FIBRONEER-IPF and FIBRONEER-ILD phase 3 trial results, which demonstrated that nerandomilast significantly slowed forced vital capacity decline versus placebo. Nerandomilast is the first novel IPF and PPF therapy to be approved in more than a decade. It is also the first in its class: a preferential phosphodiesterase 4B (PDE4B) inhibitor.
"One of the advantages of the new antifibrotic is it doesn't require lab monitoring, so patients don't have to go draw their blood every month or every three months," Dr. Carmona Porquera says. "It also seems to have less liver toxicity and fewer side effects, like diarrhea."
With the addition of nerandomilast, pulmonologists have more therapeutic options but also more questions about how best to use them in clinical practice. Dr. Carmona Porquera asks: "How should we sequence these therapies? Should they be used alone or in combination? And if we combine them, how do we balance efficacy with tolerability and side effects?"
These questions have not yet been fully addressed in clinical guidelines.
For now, pulmonary medicine physicians at Mayo Clinic collaborate with pharmacists specializing in ILD who help monitor patients for side effects and support an individualized treatment approach.
"We discuss challenging cases as a group, learn from each other's experience and tailor treatment to the needs of each patient while adapting our approach as the evidence evolves," Dr. Carmona Porquera says.
For more information
Refer a patient to Mayo Clinic.