Novel blood test helps evaluate severity in pulmonary arterial hypertension, a rare lung disease

Researchers at the National Institutes of Health have found that a novel blood test can be used to easily evaluate disease severity in patients with pulmonary arterial hypertension (PAH) and predict survivability. PAH is a rare, life-threatening condition that causes unexplained high blood pressure in the lungs. In early clinical studies, the researchers showed the test to significantly improve upon conventional tests, some of which use invasive tools.

Computed tomography 3D surface rendering of the lungs and heart from a patient with pulmonary arterial hypertension demonstrating trachea and major airways (yellow), an enlarged heart (red), enlarged main pulmonary artery (large blue vessel on top of heart) and thinning of the peripheral pulmonary vessels (blue). Marcus Y. Chen, M.D., NHLBI

The new blood test measures DNA fragments shed by damaged cells. Researchers found that these fragments, called cell-free DNA, were elevated in the blood of patients with PAH and increase with disease severity. If future studies confirm the findings, this first-of-its-kind blood test for PAH patients could allow doctors to intervene faster to prevent or delay progression of the disease and possibly save lives. Cell-free DNA is a relatively new analytical technique that is growing in its potential medical uses, which include the early detection of heart- and lung-transplant rejection as well as early detection of cancer.  

The study was funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Clinical Center, both part of NIH. The findings will appear online in the journal Circulation, a publication of the American Heart Association.

PAH is a rare form of pulmonary hypertension that can cause difficulty breathing, chest pain, and fatigue. The disease, whose exact cause is unknown, is estimated to affect less than 50,000 people in the United States, according to the NIH’s Genetic and Rare Diseases Information Center. It is characterized by progressive narrowing and blockage of the small pulmonary arteries of the lungs, strain on the right side of the heart, and eventual death from heart failure. The damage to the lung in severe cases can require lung transplantation. Patients with PAH have a high death rate, and the condition mostly affects women. Despite treatment advances, it currently has no cure.

Current tests used to monitor PAH severity rely on established risk prediction scores based on clinical symptoms and on the use of an invasive catheter to measure pressure in the lungs. Doctors sometimes use echocardiography, or heart imaging, to measure pressures in the heart as an indirect measurement of lung pressure, but these tests tend to lack reliability and sensitivity.

“Researchers have been actively searching for novel, less-invasive approaches to evaluate PAH severity, disease progression, and response to therapy for more than a decade. These cell-free DNA analyses represent progress toward that goal,” said study co-author Michael A. Solomon, M.D., M.B.A., who is part of the NHLBI Cardiovascular Branch and co-director of the NIH Clinical Center Pulmonary Arterial Hypertension Section.

Sean Agbor-Enoh, M.D., Ph.D., study co-author and chief of the NHLBI’s Laboratory of Applied Precision Omics, agreed. “Here we’re proposing a one-time test where you collect a vial of blood from a patient and use that to predict survival. We’re very encouraged by the early results.”

 In the current study, the research team analyzed cell-free DNA from blood samples taken from 209 adult patients, predominately women, diagnosed with PAH at two large U.S. medical centers. The researchers compared the results to cell-free DNA measured from a control group of 48 healthy volunteers without PAH at the NIH Clinical Center. 

They found that cell-free DNA was elevated in patients with PAH, and also found that cell-free DNA concentrations increased in proportion to the severity of the disease. Patients with the highest level of cell-free DNA had a 3.8 times greater risk of either death or a need for lung transplantation compared to those with the lowest level of cell-free DNA, the researchers said.

Further analyses of cell-free DNA samples revealed that multiple tissue types – including the heart, blood vessels, fat tissue, and inflammatory cells circulating in the blood – were affected by PAH. The new blood test will allow researchers to better pinpoint the specific tissues involved in the PAH disease process. This knowledge may lead to new drug interventions for PAH, whose current treatment options may slow but not halt or reverse disease progression.

In addition to funding from the Intramural Research Program of the NHLBI, this research is supported by the NIH Clinical Center Research Award for Staff Clinicians Program, the NIH Distinguished Scholar Award, the Lasker Clinical Research Scholars Program, and the Intramural Research Programs of the NIH Clinical Center. 

FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations

The Food and Drug Administration has granted accelerated approval to mobocertinib for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to select patients with the above mutations for mobocertinib treatment.

Approval was based on Study 101, an international, non-randomised, open-label, multicohort clinical trial (NCT02716116) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

Efficacy was evaluated in 114 patients whose disease had progressed on or after platinum-based chemotherapy. Patients received mobocertinib 160 mg orally daily until disease progression or intolerable toxicity.

The main efficacy outcome measures were overall response rate (ORR) according to RECIST 1.1 as evaluated by blinded independent central review (BICR) and response duration. The ORR was 28% (95% CI: 20%, 37%) with a median response duration of 17.5 months (95% CI: 7.4, 20.3).

The most common adverse reactions (>20%) were diarrhoea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.

Product labelling includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhoea.

The recommended mobocertinib dose is 160 mg orally once daily until disease progression or unacceptable toxicity.

Story published courtesy of ecancer

NIH-funded study finds teens prefer mint and mango vaping flavors

A new analysis suggests that teens prefer mint and mango as their vaping flavors of choice for e-cigarettes.

E-cigarette. Photo credit: Medical News Today

 Previous research showed that teens were attracted to nicotine vaping by the candy and fruit-flavored products offered by manufacturers. Products and trends are quickly evolving, and estimates of the specific e-cigarette flavors teens use are lacking; therefore, scientists wanted to find out which flavors are now preferred by teens. The report, published in JAMA, was supported by the National Institute on Drug Abuse (NIDA), the National Cancer Institute (NCI), and the U.S. Food and Drug Administration Center for Tobacco Products. NIDA and NCI are parts of the National Institutes of Health.

The study focused on JUUL products, the most widely used brand, which is available in multiple flavors. Data were from the 2019 Monitoring the Future (MTF) study, which annually surveys eighth, 10th, and 12th grade students in U.S. schools. A randomly-selected third of MTF respondents were asked, “Which JUUL flavor do you use most often?”

The 2019 data suggests that among both 12th and 10th graders, mint and mango ranked first and second (at about 47% and 24% for seniors; 44% and 27% for 10th graders). Among eighth graders, mango was most popular at 34%, followed by mint at 29%. In all grades, fruit flavoring was ranked third, followed by “Other.” Menthol was among the least popular (less than 2.3% for eighth graders; less than 3% for 10th graders and less than 6% for seniors).

The overall 2019 Monitoring the Future vaping data released last month showed a significant increase in past month vaping of nicotine in each of the three grade levels since last year. Additional findings from the 2019 Monitoring the Future Survey, documenting the use of and attitudes about marijuana, alcohol and other drugs, will be released in December.

2.4 billion people living in countries with tobacco preventive measures

Many governments are making progress in the fight against tobacco, with 5 billion people today living in countries that have introduced smoking bans, graphic warnings on packaging and other effective tobacco control measures four times more people than a decade ago, according to WHO.

Smoking leads to disease and disability and harms nearly every organ of the body – CDC

A new WHO report also shows many countries are still not adequately implementing policies, including helping people quit tobacco, that can save lives from tobacco.

According to the WHO, the focus of the latest report is on the progress countries have made to help tobacco users quit. It is being launched today in Brazil, a country that has become the second, after Turkey, to fully implement all the MPOWER measures at the highest level of achievement.

The MPOWER measures include monitoring tobacco use and prevention policies, protecting people from tobacco smoke; offering help to quit tobacco use; warning people about the dangers of tobacco; enforcing bans on tobacco advertising, promotion and sponsorship; and raising taxes on tobacco.

Dr Tedros Adhanom Ghebreyesus, WHO Director-General, said governments should implement cessation services as part of efforts to ensure universal health coverage for their citizens.

“Quitting tobacco is one of the best things any person can do for their own health,” said Dr Tedros. “The MPOWER package gives governments the practical tools to help people kick the habit, adding years to their life and life to their years.”

Progress is being made, with 2.4 billion people living in countries now providing comprehensive cessation services (2 billion more than in 2007). But only 23 countries are providing cessation services at the best-practice level, making it the most under-implemented MPOWER measure in terms of number of countries offering full coverage.

Tobacco cessation services include national toll-free quit lines, “mCessation” services to reach larger populations via mobile phones, counselling by primary health care providers and cost-covered nicotine replacement therapy.

Michael R. Bloomberg, WHO Global Ambassador for Noncommunicable Diseases and Injuries  and founder of Bloomberg Philanthropies, said the report shows government-led efforts to help people quit tobacco work when properly implemented.

“More countries are making tobacco control a priority and saving lives, but there’s still much more work to be done,” said Mr Bloomberg. “The WHO’s new report shines a spotlight on global efforts to help people quit using tobacco and it details some of our most important gains.”

The report, funded by Bloomberg Philanthropies, showed that while only 23 countries have implemented cessation support policies at the highest level, 116 more provide fully or partially cost-covered services in some or most health facilities, and another 32 offer services but do not cost-cover them, demonstrating a high level of public demand for support to quit.

Tobacco use has also declined proportionately in most countries, but population growth means the total number of people using tobacco has remained stubbornly high. Currently, there are an estimated 1.1 billion smokers, around 80% of whom live in low- and middle-income countries (LMICs).

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