PULMONARY ARTERIAL HYPERTENSION: A blood test to assess its severity

PULMONARY ARTERIAL HYPERTENSION: A blood test to assess its severity

PAH is a rare and life-threatening condition that causes unexplained high blood pressure in the lungs. PAH can cause difficulty breathing, chest pain and fatigue. The disease, the exact cause of which is unknown, is characterized precisely by narrowing and progressive blockage of the small pulmonary arteries of the lungs, tension on the right side of the heart and can lead to death from heart failure. Lung damage in the most severe cases may require a lung transplant. Patients with PAH have a high mortality rate and the condition mainly affects women. Despite advances in treatment, there is currently no cure.

Measuring elevated cell-free DNA in patients with PAH

Current tests used to monitor the severity of PAH rely on risk prediction scores based on clinical symptoms and the use of an invasive catheter to measure pressure in the lungs. Doctors sometimes use echocardiography, or cardiac imaging, to measure pressures in the heart as an indirect measure of lung pressure, but these tests tend to lack reliability and sensitivity. Thus, many scientists are looking for new, less invasive approaches to assess PAH severity, disease progression, and response to treatment.

Cell-free DNA analysis is a technique of the future, underlines the co-author of the study, Dr. Michael A. Solomon, of the pulmonary arterial hypertension department of the NIH Clinical Center. The new blood test measures DNA fragments released by damaged cells. Levels of these cell-free DNA fragments, elevated in the blood of patients with PAH, increase with disease severity. If the specificity and sensitivity of the test were confirmed by larger studies, then doctors would be able to intervene more quickly to prevent or delay disease progression and potentially save lives.

A first proof of concept is provided, with the analysis of cell-free DNA of blood samples taken from 209 adult patients, mainly women, diagnosed with PAH compared to the cell-free DNA of 48 volunteers free of PAH and in good health. The analysis confirms that:

  • cell-free DNA is elevated in patients with PAH;
  • cell-free DNA levels increase with disease severity;
  • patients with the highest level of cell-free DNA have a 3.8 times higher risk of death or the need for lung transplantation, vs those with the lowest level of cell-free DNA;
  • several types of tissues – including the heart, blood vessels, fatty tissues and inflammatory cells circulating in the blood are found to be affected by PAH. The new blood test makes it possible to better identify the specific tissues involved in the pathological process.

Finally, the research provides an illustration of the cell-free DNA analytical technique, a relatively new technique whose medical uses are growing, including the early detection of heart and lung transplant rejection as well as the early detection of cancer.

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