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Researchers at the University of Pittsburgh have developed a nasal swab test for kids that diagnoses specific asthma subtype, or endotype. This non-invasive approach could help clinicians prescribe medications more precisely and pave the way for research toward better treatments for lesser-studied asthma types, which have been difficult to diagnose accurately until now.
Published today in JAMA, the findings are based on data from three independent U.S.-based studies that focused on Puerto Rican and African American youths, who have higher rates of asthma and are more likely to die from the disease than their non-Hispanic white counterparts.
“Asthma is the most common chronic disease of childhood, and it disproportionately affects Black and Puerto Rican children, so it’s essential that we develop new therapies to better treat these young patients,” said senior author Juan Celedón, M.D., Dr.P.H., professor of pediatrics at Pitt and chief of pulmonary medicine at UPMC Children’s Hospital of Pittsburgh. “Because asthma is a highly variable disease with different endotypes, which are driven by different immune cells and respond differently to treatments, the first step toward better therapies is accurate diagnosis of endotype.”
Traditionally, asthma has been classified into endotypes known as T2-high or T2-low based on the amount of T helper 2 inflammation present. More recently, T2-low has been split into two endotypes: T17-high, which has less T helper 2 inflammation and more T helper 17 inflammation, and low-low, which has low levels of both types of inflammation.
Precise diagnosis of endotype usually involves genetic analysis of a lung tissue sample taken by a procedure called a bronchoscopy, which is done under general anesthesia. For children, especially those with milder disease, it’s not feasible or ethical to perform this invasive procedure, so clinicians have had to rely on imperfect tools, including immune markers in the blood, lung function and whether or not they have allergies.
“These tests allow us to presume whether a child has T2-high disease or not,” said Celedón. “But they are not 100% accurate, and they cannot tell us whether a child has T17-high or low-low disease. There is no clinical marker for these two subtypes. This gap motivated us to develop better approaches to improve the accuracy of asthma endotype diagnosis.”
Celedón and his team, including first authors Molin Yue, M.S., a Pitt graduate student, and Kristina Gaietto, M.D., M.P.H., instructor of pediatrics at Pitt, collected nasal samples from 459 youth across three different studies. Then they analyzed the expression of eight T2 and T17 signature genes.
As expected, analysis of nasal swab samples revealed a patient’s endotype. Across studies, 23% to 29% of participants had T2 high, 35% to 47% had T17-high and 30% to 38% had low-low endotype.
For treating severe T2-high asthma, there is a powerful new class of drugs called biologics, which target the immune cells that drive disease. However, no available asthma biologics directly target T17-high and low-low endotypes.
“We have better treatments for T2-high disease, in part, because better markers have propelled research on this endotype,” said Celedón. “But now that we have a simple nasal swab test to detect other endotypes, we can start to move the needle on developing biologics for T17-high and low-low disease.”
This rapid test for asthma endotype could also help push forward other areas of asthma research.
“One of the million-dollar questions in asthma is why some kids get worse as they enter puberty, some stay the same and others get better. Before puberty, asthma is more common in boys, but the incidence of asthma goes up in females in adulthood,” said Celedón. “Is this related to endotype? Does endotype change over time or in response to treatments? We don’t know. But now that we can easily measure endotype, we can start to answer these questions.”
Gustavo Matute-Bello, M.D., acting director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH) added, “Having tools to test which biological pathways have a major role in asthma in children, especially those who have a disproportionate burden of disease, may help achieve our goal of improving asthma outcomes. This research has the potential to pave the way for more personalized treatments, particularly in minority communities. More studies are needed.”
Other authors on the study were Yueh Ying Han, Ph.D., Franziska J. Rosser, M.D., M.P.H., Zhongli Xu, Christopher Qoyawayma, B.S.E., Erick Forno, M.D., M.P.H., and Wei Chen, Ph.D., all of Pitt and UPMC; and Edna Acosta-Perez, Ph.D., and Glorisa Canino, Ph.D., both of the University of Puerto Rico.