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PITTSBURGH — A novel diagnostic test using just a nasal swab could transform how doctors diagnose and treat childhood asthma. Researchers at the University of Pittsburgh have developed this non-invasive approach that, for the first time, allows physicians to precisely identify different subtypes of asthma in children without requiring invasive procedures.
Until now, determining the specific type of asthma a child has typically required bronchoscopy, an invasive procedure performed under general anesthesia to collect lung tissue samples. This limitation has forced doctors to rely on less accurate methods like blood tests and allergy screenings, potentially leading to suboptimal treatment choices.
“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,” says senior author Dr. Juan Celedón, a professor of pediatrics at the University of Pittsburgh and chief of pulmonary medicine at UPMC Children’s Hospital of Pittsburgh, in a statement.
3 subtypes of asthma
The new nasal swab test analyzes the activity of eight specific genes associated with different types of immune responses in the airways. This genetic analysis reveals which of three distinct asthma subtypes, or endotypes, a patient has: T2-high (involving allergic inflammation), T17-high (showing a different type of inflammatory response), or low-low (exhibiting minimal inflammation of either type).
The research team validated their approach across three separate studies involving 459 young people with asthma, focusing particularly on Puerto Rican and African American youth, populations that experience disproportionately higher rates of asthma-related emergency room visits and complications. According to the researchers, Puerto Rican children have emergency department and urgent care visit rates of 23.5% for asthma, while Black children have rates of 26.6% — both significantly higher than the 12.1% rate among non-Hispanic white youth.
The findings, published in JAMA, challenge long-held assumptions about childhood asthma. While doctors have traditionally believed that most cases were T2-high, the nasal swab analysis revealed this type appears in only 23-29% of participants. Instead, T17-high asthma accounted for 35-47% of cases, while the low-low type represented 30-38% of participants.
“These tests allow us to presume whether a child has T2-high disease or not,” explained 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.”
Precision medicine for patients
This breakthrough carries significant implications for treatment. Currently, powerful biological medications exist for T2-high asthma, but no available treatments specifically target T17-high or low-low types. The availability of this new diagnostic test could accelerate research into treatments for these previously understudied forms of asthma.
“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.”
The test could also help researchers understand how asthma evolves throughout childhood and adolescence. Celedón noted that one of the “million-dollar questions in asthma” involves understanding why the condition affects children differently as they age.
“Before puberty, asthma is more common in boys, but the incidence of asthma goes up in females in adulthood. Is this related to endotype? Does endotype change over time or in response to treatments? We don’t know,” he says. “But now that we can easily measure endotype, we can start to answer these questions.”
Dr. Gustavo Matute-Bello, acting director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, emphasizes the potential impact of this diagnostic advancement. “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,” he says. “This research has the potential to pave the way for more personalized treatments, particularly in minority communities.”
Paper Summary
Methodology
The research team collected nasal epithelial samples using gentle swabs from the nasal passages of participants across three different studies. These samples were analyzed for the activity of eight specific genes associated with different types of immune responses. Using advanced statistical methods, they grouped patients into three distinct profiles based on their gene activity patterns. The team also collected traditional diagnostic information, including allergy tests, lung function measurements, and various biomarkers from blood and breath tests, to validate their findings.
Results
The findings revealed three clear patterns across all three studies:
T2-high asthma, characterized by elevated activity of allergy-related genes, appeared in roughly one-quarter of participants (23-29%). These patients typically showed higher levels of traditional allergy markers in their blood, including immunoglobulin E (IgE) and eosinophils (a type of white blood cell).
T17-high asthma, marked by increased activity of different inflammatory genes, was more common, affecting 35-47% of participants. This type involves a different kind of immune response than traditional allergic asthma.
The third type, termed “low-low,” showed minimal activity of either gene set and appeared in 30-38% of participants. Surprisingly, many children with this type still tested positive for allergies, suggesting that the presence of allergies alone doesn’t determine asthma type.
Limitations
The researchers acknowledge several important limitations. First, while nasal cells provide valuable information, they may not perfectly mirror all aspects of lung inflammation. Additionally, the study captured just one moment in time for each participant – we don’t yet know if these asthma types remain stable or change over time.
The research focused primarily on Puerto Rican and African American youth, which means the findings might not apply equally to all populations. However, this focus was intentional given the higher burden of asthma in these communities.
Discussion and Takeaways
This research marks a significant shift in our understanding of childhood asthma. Traditionally, doctors have often assumed that most childhood asthma was T2-high, largely because this type is easier to identify with existing tests. The discovery that this type actually represents a minority of cases helps explain why some current treatments work better for some patients than others.
The availability of a simple nasal test could accelerate the development of new treatments for T17-high and low-low asthma types, which together represent the majority of cases but currently lack targeted therapies.
Funding and Support
The research received funding from multiple National Institutes of Health grants. The studies also received support from pharmaceutical companies including Merck, Pharmavite, and GSK, who provided medications used in the research.
Publication Details
The study, titled “Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth,” was published in JAMA on January 2, 2025. The research represents a collaboration between scientists at the University of Pittsburgh, UPMC Children’s Hospital of Pittsburgh, and the University of Puerto Rico.
