New noninvasive asthma test may help doctors tailor treatment for kids

Impacting millions of children in the U.S. alone, asthma can be particularly problematic to diagnose with specificity — leaving the majority of kids without treatments that target their subtype of the condition.

Using a new, noninvasive nose swab test, researchers at the University of Pittsburgh have for the first time detected multiple asthma subtypes in children with the condition, which previously could only be recognized through an invasive procedure called a bronchoscopy.

The team's study, published in the Journal of the American Medical Association on Jan. 2, is also the first to pinpoint genes involved in the various asthma subtypes using the nose swab test.

"Asthma is the most common chronic respiratory disease in children around the world," said Juan Celedón, a professor of pediatrics at Pitt, division chief of pulmonary medicine at UPMC Children's Hospital of Pittsburgh and senior author on the paper. "In the U.S., it affects 6 million children, and even though it affects children of all races and ethnicities, Puerto Ricans and Blacks are most heavily affected — not only with regard to the frequency of asthma, but also with the severity of the disease."

This is true in Allegheny County. A 2022 county health assessment report found that Black kids ages 5 to 17 had asthma at a rate six times higher than white children in 2020.

The findings give clues as to why some people don't respond to treatment.

Asthma and allergy biologics have become popular approaches, due to their ability to target specific inflammation pathways, as opposed to the general approach of an inhaler. But the treatments don't work for everyone. The researchers want to expand on the study's findings to tailor treatments to other asthma patients, similar to how breast cancer treatment became personalized based on subtypes including triple negative and HER2-positive breast cancers.

The first step in identifying the causes of certain diseases and developing treatments for them, said Celedón, is to select patients to study who might benefit.

So researchers pulled from three different cohorts of 460 children, ages 9 to 20 — including Pittsburgh kids — and swabbed their noses for DNA. They then sequenced the genes to discover which kind of asthma each had. As the disease impacts Puerto Rican and Black populations more, they made up most of the cohorts.

The nasal swab technique is a welcome alternative to a bronchoscopy, a procedure that involves sedating a patient and taking lung tissue samples. It's expensive, involved and not recommended for kids or people with mild to moderate asthma, which makes up the majority of asthma cases.

"There is no way you're going to do a bronchoscopy with mild to moderate disease," said Celedón, who is also a professor of medicine, epidemiology and human genetics at Pitt. "True severe asthma in kids is very rare — it's estimated that 5% or fewer of kids have true severe asthma. Kids may have poorly controlled asthma, which is very common ... but the vast majority of kids have mild to moderate asthma."

From those nasal swab samples, the researchers looked at genes that deal with T cells, involved in the body's immune response and inflammation.

Experts already know about two asthma subtypes involving T cells. T2-high asthma is more likely to be associated with exposure to allergens and irritants. People with this asthma subtype have a high level of T2 cells present, leading to robust immune response, allergic reactions and inflammation in the airways.

Current treatments such as antibody shots for asthma work well for people with this subtype, because they target specific inflammatory cells in the body, amped up from an immune response.

But T2-low asthma is often not related to allergens and is more likely to show up in people with obesity and those over 65. This could be why antibody treatments don't always work for these groups. It's like shooting a bunch of arrows at the wrong target.

And the researchers were able to detect another asthma subtype involving T17 cells — a type of immune marker — called T17-high.

Through gene analysis, the study concluded that T2-high patients were more likely to be Puerto Rican, while T17-high patients were more likely to be Black.

Celedón said it's "90 to 95% likely" that these racial and ethnic inequities are caused by environmental and socioeconomic factors, such as air pollution, smoking and obesity.

"Omics (the study of genes) can complement this information and help us understand how environment shapes disease," he said. "And then we'll have better prevention. So the two things are complementary."

His team is already working on a longer-term study to see whether these subtypes change after puberty or over a person's lifespan. They're also in the process of checking in with one of the three cohorts to see how their health has changed over time.

And they want to learn more about what's leading to different asthma subtypes, as gene pathways involved with the asthma subtypes studied in the paper were also linked to cancer risk, liver function and integrity of the airway lining.

"Is obesity more associated with the T17-high, T2-high, or both? What about air pollution?," he asked. "It's good to understand that for prevention and treatment."

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