A recent Vanderbilt University Medical Center-led study of relatives of patients with familial pulmonary fibrosis (FPF), a form of idiopathic pulmonary fibrosis (IPF) that runs in families, studied the risk factors for progressive early disease in a group of asymptomatic relatives of patients with FPF.
The research focused on the very early stages of FPF, a serious progressive lung disease where for unknown reasons scar tissue builds up in the lungs over time. The analysis determined that even minor early changes in the lungs can signal progression of the disease.
The study, “Progressive Early Interstitial Lung Abnormalities in Persons At-Risk for Familial Pulmonary Fibrosis,” demonstrates that individuals with very early disease can be identified relatively easily using high resolution chest CT scan. Individuals with very early changes in the lungs that are detectable on CT, but who have not yet developed symptoms, are the ideal population to enroll in future clinical trials to identify treatments that prevent progression toward symptomatic FPF, said Margaret Salisbury, MD, assistant professor of Medicine and first author of the study.
People with IPF develop symptoms such as shortness of breath and cough and eventually require oxygen. Survival time after diagnosis of symptomatic disease is typically around three to five years. Patients often die of respiratory failure.
The study was published in the American Journal of Respiratory and Critical Care Medicine. National Jewish Health in Denver contributed to the study.
Approximately 20-25% of all cases of IPF are familial, meaning that there are two or more blood-related relatives who have the disease, Salisbury said. Around 1 in 200 U.S. adults over 65 are living with IPF.
The study used a VUMC registry of families with FPF.
“Blood relatives of those who have pulmonary fibrosis can join the study even if they aren’t known to have pulmonary fibrosis,” Salisbury said. This group of people is known as the “at-risk for FPF cohort” — those who are asymptomatic, are not known to have IPF, but are at risk to develop it in the future, she said.
Those relatives between 40 and 75 are eligible to come to VUMC for study visits over a period of time where they are screened for subclinical or asymptomatic early disease using a CT scan of the chest as well as pulmonary function tests and blood tests.
“The main goal of the study is to evaluate characteristics, particularly CT findings, that are associated with subclinical disease — abnormal changes on CT that are getting worse over time or the development of symptomatic pulmonary fibrosis in these at-risk individuals,” Salisbury said.
The changes the study investigators looked for on the CT scans are called interstitial lung abnormalities (ILAs), as defined by the Fleischner Society, an international multidisciplinary medical society for thoracic radiology. The society identifies ILAs as involving 5% or more of a lung zone, but the researchers wanted to see if the changes are relevant when they are present in less than 5% of lung involvement.
They grouped patients based on whether they had ILAs in less than or more than 5% of the lung zone, and then compared those patient outcomes to patients with no interstitial abnormalities on their enrollment CT scans.
“We found that even people who had abnormalities present, but at less than 5% (called mild ILAs), had a significantly increased risk to go on to have worsening changes over time, or to develop IPF,” Salisbury said. “They had about nine times the risk of going on to progressive disease, compared to people who had no abnormalities at enrollment. And people who had moderate ILAs (more than 5% of the lungs involved) had 17 times the odds of progression as those without ILAs,” she said.
Salisbury said the study is ongoing, and patients are still being enrolled.
“Our goal, and the goal of a lot of other people in the field, is to eventually do clinical trials to see if IPF, meaning symptomatic disease, can be prevented,” she said. “If we want to prevent something, we have to know what it looks like in its very earliest stages. This study provides very useful information about people that we could target for enrollment in future clinical trials trying to prevent the development of the progression of symptomatic pulmonary fibrosis.”
