Asthma comes in different subtypes, but diagnosing those subtypes, also known as endotypes, has historically been difficult – until now. Recent research presents an alternative: a nasal swab test that scientists in the US say accurately diagnoses a child’s asthma subtype.
Researchers used the new tests in three studies of mostly Puerto Rican and African American children – groups disproportionately affected by asthma, reports The Washington Post.
Understanding a child’s asthma type can help target treatment, but precisely pinpointing asthma endotype has relied on an invasive procedure that can be difficult to perform on a child.
“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,” said Juan Celedón, a professor of paediatrics at the University of Pittsburgh, chief of pulmonary medicine at UPMC Children’s Hospital of Pittsburgh and the study’s senior author.
To make diagnosis easier and better identify asthma subtypes, researchers developed a nasal swab test instead, analysing samples from 459 children between six and 20-years-old across the three studies of Puerto Rican and African American youths.
The test looked for three asthma endotypes: T2-high or T17-high, which involve high Type-2 or Type-17 inflammation in the lungs, and “low-low” asthma, which involves low levels of both inflammation types.
T2-high asthma has often been considered the most common type of asthma in school-age children, the researchers wrote in their findings, published in JAMA. But the genetic analysis revealed that 23% to 29% of the study participants had T2-high asthma while 35% to 47% had T17-high asthma, and 30% to 38% had low-low asthma.
A better understanding of asthma subtypes in young people who are members of minority groups may lead to “trials of much-needed therapies for T17-high asthma”, the researchers concluded.
Though targeted biologic drugs exist for T2 asthma subtypes, there are no biologics on the market for T17 or low-low asthma.
Study details
Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth
Molin Yue, Kristina Gaietto, Juan Celedón et al.
Published in JAMA Network on 2 January 2025
Abstract
Importance
T helper 2 (T2) cells and T helper 17 (T17) cells are CD4+ T cell subtypes involved in asthma. Characterising asthma endotypes based on these cell types in diverse groups is important for developing effective therapies for youths with asthma.
Objective
To identify asthma endotypes in school-aged youths aged 6 to 20 years by examining the distribution and characteristics of transcriptomic profiles in nasal epithelium.
Design, Setting, and Participants
Cross-sectional analysis of nasal epithelial samples from 3 studies of youths with asthma aged 6 to 20 years: Stress and Treatment Response in Puerto Rican and African American Children with Asthma (STAR; N = 156), Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR; N = 237), and Vitamin D Kids Asthma (VDKA; N = 66).
Main Outcomes and Measures
The primary outcome was nasal epithelial transcription profiles of 3 T2 and 5 T17 pathway genes. Clinical characteristics, total and allergen-specific immunoglobulin E (IgE), blood eosinophils, and lung function were compared across profiles in all studies.
Results
Mean ages for STAR, EVA-PR, and VDKA participants were 14.2, 15.4, and 10.3 years, respectively. The percentage of female participants ranged from 41% to 53.2% across studies. The predominant race or ethnicity was Puerto Rican in EVA-PR (100%) and Black or African American in STAR (71.8%) and VDKA (57.6%). Three transcriptomic profiles were identified: high T2 expression (T2HIGH), high T17 expression (T17HIGH), and low expression of both pathways (T2LOW/T17LOW). Across studies, T2HIGH was present in 23% to 29% of participants, T17HIGH in 35% to 47%, and T2LOW/T17LOW in 30% to 38%. In each study, median total IgE and blood eosinophils for the T2HIGH profile was higher than for the T2LOW profiles (IgE, 584-869 vs 105-382 IU/mL; eosinophils, 343-560 vs 164-413 cells/mL). Of the participants in all profiles, at least 50% had 1 or more positive allergen-specific IgEs. A differential expression meta-analysis identified 3516 and 2494 differentially expressed genes for the T2HIGH and T17HIGH profiles, respectively. The T17HIGH profile was associated with interleukin 17 and neutrophil signalling pathways and the T2HIGH profile was associated with interleukin 13 signalling pathways.
Conclusions and Relevance
Nasal transcriptomic profiles consistent with T2-high, T17-high, and T2-low/T17-low endotypes occurred in similar proportions across 3 studies of predominantly racially and ethnically minoritised youths with asthma. Most participants had T2-low asthma endotypes and sensitisation to one or more allergens was common among these endotypes.
The Washington Post article – New nasal test said to ID asthma subtypes in kids (Restricted access)
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Urgent need to improve asthma control worldwide – global study
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