Intermountain Healthcare Researcher Receives National Grant to Identify Genetic Markers of Lung Disorder

An Intermountain Healthcare researcher has been awarded a prestigious grant to study a vexing problem: why do approximately three percent of patients who experience pulmonary  embolism – a blood clot in the arteries in the lungs  – have their blood clots fail to resolve even with proper treatment with blood thinning medications?  
 
“We really don’t understand why some people develop chronic pulmonary emboli that fail to resolve with anticoagulant treatment,” said Mark W. Dodson, MD, PhD, medical director of the CTEPH program at Intermountain Healthcare.  
 
Through the ENTELLIGENCE Young Investigator Program grant, Dr. Dodson and his team, who have already identified clusters of families in which chronic blood clots of the lungs are more likely to develop, hope to identify genetic markers for the disease. 
 
Called Chronic Thromboembolic Pulmonary Hypertension (CTEPH), it’s a form of high blood pressure in the lungs caused by scar-like tissue formation within the arteries in the lungs. These scars form from unresolved pulmonary emboli, and block or narrow the arteries in the lungs. 
 
“The blood clots essentially remodel into fibrous scar tissue inside the pulmonary arteries and block blood flow within these arteries, raising the pressure,” said Dr. Dodson. 
 
In the United States, about 5,000 people are diagnosed with CTEPH each year. It’s estimated that one in every 25 people who have had a blood clot in the lungs is at risk for getting CTEPH.
 
The most common symptom is shortness of breath, which can be debilitating for patients. 
 
The recommended treatment for CTEPH is surgically opening up the chest to remove the lining of the arteries and the scar tissue with it. This is an option for patients who are strong enough to undergo that kind of intense surgery.
 
CTEPH can be challenging to diagnose early because its primary symptom – persistent shortness of breath – is experienced by about half of all pulmonary embolism patients. 
 
Clinicians get so used to hearing this, they may not do the testing to evaluate for CTEPH, such as an echocardiogram or lung ventilation-perfusion scan. “The typical age of onset of CTEPH is also in the mid-60s, so these patients could have other conditions like asthma or Chronic Obstructive Pulmonary Disease (COPD)that could also cause shortness of breath,” Dr. Dodson noted. 
 
In a paper published in the journal, Chest, Dr. Dodson and his team identified CTEPH patients from Intermountain Healthcare and the University of Utah, then used the Utah Population Database to assess whether CTEPH clusters in families. 
 
They found 27 high-risk CTEPH pedigrees – and discovered that many patients with CTEPH were in fact related to someone else with the disease. It wasn’t necessarily a close familial relation like parent to child, Dr. Dodson said, but more often second cousin to second cousin or aunt to niece. 
 
Because CTEPH patients tend to share distant familial relationships, they are often not aware that they have another family member with the same disease. The clustering of disease into pedigrees suggests that there are genetic risk factors for the disease. 
 
The ENTELLIGENCE research grant, which is for one year, will be used to build on that research to do whole genome sequencing of CTEPH patients from those high-risk pedigrees, Dr. Dodson said. 
 
“We know that those patients are related, so we only need to focus on what they share in terms of their DNA. For second cousins, that’s about three percent. It really allows you to filter out genes that are not likely to be involved and hone in on the genes that could be causing this,” he said. 
 
If researchers can find a biomarker – a measurable indicator of the severity or presence of disease – for CTEPH, pulmonary embolism patients could be screened for risk of CTEPH. With this knowledge, doctors could work to prevent CTEPH from developing in patients at risk, rather than treating the consequences of CTEPH after the disease has occurred. 
 
“There’s basically nothing known about the genetics of CTEPH and no known genetic risk factors so we can predict who’s going to get the disease,” Dr. Dodson said. “I think this would really change how we manage people with pulmonary embolism.” 

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