Nasal Swabs Identify Kids’ Asthma Subtypes

A simple, noninvasive nasal swab identified a predominance of T2-low asthma subtypes in racial and ethnic minority pediatric patients, based on data from three independent studies of children and youth aged 6-20 years with asthma.

“T helper 2 (T2) and T helper 17 (T17) cells are CD4+ cell subtypes involved in asthma. At present, we lack noninvasive tests to identify asthma subtypes or endotypes based on these cell types in school-aged children and adolescents,” said corresponding author Juan C. Celedon, MD, of the University of Pittsburgh, Pennsylvania, in an interview.

“Identification of these endotypes is key to better understand causal pathways and develop effective treatments for asthma in youths, particularly those in minorized groups with high asthma burden, such as Puerto Rican and Black youths,” said Celedon. “We aimed to identify asthma endotypes in school-aged youth aged 6-20 years by studying the distribution and characteristics of transcriptomic (or gene expression) profiles in nasal epithelial samples,” he said.

The study population included 156 individuals from the Stress and Treatment Response in Puerto Rican and African American Children with Asthma (STAR), 237 from the Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR), and 66 from the Vitamin D Kids Asthma (VDKA) studies. The primary outcome was an analysis of eight genes in the nasal epithelium (three T2 genes and five T17 genes). The researchers also compared clinical characteristics, total and allergen-specific immunoglobulin E, blood eosinophils, and lung function across the studies.

The collective data from the three studies were published in JAMA.

The mean ages of the participants in the STAR, EVA-PR, and VDKA were 14.2 years, 15.4 years, and 10.3 years, respectively, and the percentage of women ranged from 41% to 53.2%. All participants in the EVA-PR study were Puerto Rican, and a majority of those in the STAR and VKDA were Black or African American (71.8% and 57.6%, respectively).

The researchers identified three transcriptomic profiles: High T2 expression (T2-high), high T17 expression (T17-high), and low expression of T2 and T17 (T2-low/T17-low). T2-high, T17-high, and T2-low/T17-low profiles were present in 23%-29%, 35%-47%, and 30%-38%, respectively, of participants across all three studies.

The median total Immunoglobulin E (IgE) and blood eosinophils levels were higher for the T2-high profiles vs for the T2-low profiles, with values ranging from 584 IU/mL to 869 IU/mL vs 105 IU/mL to 382 IU/mL for IgE and from 343 cells/mL to 560 cells/mL vs 164 cells/mL to 413 cells/mL for eosinophils across the studies.

At least 50% of participants across all profiles had at least one positive allergen-specific IgE. However, the proportion was highest for those with a T2-high profile (95.5%, 91.9%, and 66.7% in the EVA-PR, STAR, and VDKA studies, respectively).

In a meta-analysis, the researchers identified 3516 differentially expressed genes for T2-high and 2494 differentially expressed genes for T17-high profiles. The T2-high profile was associated with interleukin 13 signaling pathways, whereas the T17-high profile was associated with interleukin 17 and neutrophil signaling pathways.

“T2-high asthma has often been assumed to be the most common asthma endotype in youth, largely because atopy (sensitization to at least one allergen) often coexists with asthma in this group,” Celedon told Medscape Medical News. However, the current study showed that T2-low transcriptomic profiles (including both T17-high and T2-low/T17-low) are more prevalent in data from mainly minority youth with asthma, he said.

“This study’s results should enable endotype-targeted clinical trials of new and much-needed therapies for T2-low asthma endotypes (T17-high and T2-low/T17-low) in diverse youth,” he said.

A key takeaway is that asthma with atopy is not the same as T2-high asthma, said Celedon. “In our study, atopy alone or any single biomarker (such as total immunoglobulin E or blood eosinophils) had poor accuracy to define T2-high asthma, which may explain why some persons thought to have T2-high asthma based on single biomarkers do not respond well to monoclonal antibodies for severe T2-high asthma,” he said.

The findings were limited by the cross-sectional design, Celedon noted. “We are planning longitudinal studies to assess whether and how asthma endotypes change over time, such as after puberty, or as a result of treatment, and we will be studying potential risk factors for the different asthma endotypes,” he said.

Clinical Implications

“This research was important because asthma is a heterogeneous disease with various endotypes (T2-high, T17-high, T2-low/T17-low), but most prior studies on asthma focused on T2-high endotypes,” said Payel Gupta, MD, medical director and owner of Ease Allergy Clinic, Brooklyn, New York, in an interview.

“The use of nasal transcriptomics, which is safer and more feasible for children, offered an opportunity to better understand asthma endotypes in these underserved groups, who disproportionately experience asthma-related health burdens,” said Gupta, who was not involved in the study.

Gupta said the current study challenged the assumption that T2-high asthma is the most common endotype in youth. “The study revealed that T2-low endotypes, including T17-high and T2-low/T17-low, were more prevalent. This was surprising because atopy (allergic sensitization) is commonly associated with asthma and has historically been equated with T2-high asthma,” she said. “These results highlight the need to reconsider clinical strategies, especially since a significant proportion of participants with T2-low profiles also showed allergic sensitization,” she added. The data may promote future research and the development of more tailored therapies, especially for minority groups who suffer disproportionately from asthma, she noted.

“The take-home message is that nasal transcriptomic profiling may effectively identify asthma endotypes in youth, providing insights beyond traditional biomarkers like IgE or eosinophils,” Gupta said. “This could lead to more precise endotype-driven treatments, particularly for patients with T2-low or T17-high asthma, for whom current therapies are often less effective; such testing could facilitate tailored interventions and improve outcomes for racially and ethnically minoritized youth,” she said.

Potential barriers to the use of nasal swab testing in clinical practice include accessibility and cost, Gupta said. Clinicians also may need to be taught how to interpret the test, which will take time, so the sooner the method is validated, the better for it to become more widely adopted, she said.

Looking ahead, additional research is needed in several areas, Gupta told Medscape Medical News. The findings must be validated in broader populations, including youth from diverse racial and ethnic backgrounds. Research also is needed to explore the longitudinal stability of asthma endotypes and their response to treatments, to develop biomarkers and therapeutic targets for T17-high asthma in particular, and to investigate how transcriptomic profiles correlate with bronchial profiles and real-world treatment outcomes, she said.

The three studies were supported in part by grants from the National Institutes of Health. In the VDKA study, Pharmavite provided the vitamin D and placebo capsules and GlaxoSmithKline provided the Flovent medication. In the STAR study, Merck provided the Asmanex medication. The researchers had no financial conflicts to disclose. Gupta had no financial conflicts to disclose.