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Nasal Epithelial Gene Expression May Allow Nasal Swab Diagnosis of Asthma Subtypes
The study also revealed a predominant T2-low asthma endotype in majority Puerto Rican and Black or African American youth populations.
New research has demonstrated proof of concept of using nasal epithelial gene expression to identify asthma endotypes in young people and revealed a predominant T2-low asthma endotype in ethnic minorities.1
“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,” senior investigator Juan Celedón, MD, DrPH, professor of pediatrics, University of Pittsburgh and chief of pulmonary medicine, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, said in a statement.2 “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.”
Celedón and colleagues sought to identify T helper 2 (T2) cells and T helper 17 (T17) cell endotypes of asthma in school-aged youths aged 6 to 20 years from 3 studies: 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).1
Current diagnostic tests, including assessing immune markers in the blood, lung function and the presence of allergies “allow us to presume whether a child has T2-high disease or not,” said Celedón.2 “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.”
Participants in the STAR, EVA-PR, and VDKA studies had mean ages of 14.2, 15.4, and 10.3 years, respectively. Gender was generally balanced across the studies, with the percentage of female participants ranging from 41% to 53.2% across studies. Participants in EVA-PR were 100% Puerto Rican, while participants in STAR (71.8%) and VDKA (57.6%) were mostly Black or African American.1
Celedón and colleagues identified 3 transcriptomic profiles: high T2 expression (T2HIGH), high T17 expression (T17HIGH), and low expression of both pathways (T2LOW/T17LOW). They found that across studies, T2HIGH was present in 23% to 29% of participants, T17HIGH in 35% to 47%, and T2LOW/T17LOW in 30% to 38%. Participants with the T2HIGH profile in each study had higher median total IgE and blood eosinophils than those with the T2LOW profiles (IgE, 584-869 vs 105-382 IU/mL; eosinophils, 343-560 vs 164-413 cells/mL).1
“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,” Celedón said.1 “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.”
The investigators found that at least 50% of participants including all profiles had 1 or more positive allergen-specific IgEs. Using a differential expression meta-analysis, they identified 3516 and 2494 differentially expressed genes for the T2HIGH and T17HIGH profiles, respectively. The T17HIGH profile was associated with interleukin 17 and neutrophil signaling pathways and the T2HIGH profile was associated with interleukin 13 signaling pathways.1
“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,” Gustavo Matute-Bello, MD, acting director, Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH) added.2
