Research Identifies Non-Allergy Driven Rhinoconjunctivitis Phenotypes in Children With Asthma

Alkis Togia, MD

Credit: NIAID

New research has identified novel rhinoconjunctivitis phenotypes in children with asthma which may not be allergy-driven, prompting the need for more research to better understand the pathology of rhinoconjunctivitis.¹

“Rhinoconjunctivitis phenotypes are conventionally described on the basis of symptom severity, duration and seasonality, and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level,” lead investigator Alkis Togia, MD, Branch Chief, Allergy, Asthma and Airway Biology, Division of Allergy, Immunology and Transplantation of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, and colleagues wrote.¹

Togia and colleagues conducted a study with a cohort of children with asthma in low-income urban environments that were prospectively followed with a rhinoconjunctivitis activity questionnaire. The participants had their upper and lower airway disease managed for 12 months with every 2-month visit based on standardized algorithms. The investigators identified individual rhinoconjunctivitis symptom trajectories and clusters of those trajectories and compared the clusters focusing on atopic characteristics.

Togia and colleagues identified 5 symptom clusters from the 619 children included: 2 had high symptoms (22.5%) but differed in seasonal pattern, 1 had medium symptoms (13.6%), 1 had medium nasal congestion only (20.4%), and 1 had low symptoms (43.6%). The low symptom group had 2 subgroups of if nasal corticosteroids were frequently prescribed (23.6%) or not (20.0%), and both subgroups did not have seasonal variation. The high symptom cluster group had a higher number of allergic sensitizations and family history of allergic airway disease, but allergic sensitization did not explain differences in seasonality.¹

“In children with asthma, unbiased clustering based on rhinoconjunctivitis symptom frequency, intensity, and seasonality reveals phenotypes that differ from conventional classifications,” Togia and colleagues wrote.¹ “Although allergic sensitization is more prominent in phenotypes with more severe disease, specific aeroallergen sensitization does not link to the newly identified clinical phenotypes.”

Other recent research, conducted by 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, and colleagues looked deeper into asthma pathology.²

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), 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).²

“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 in a statement.³ “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.”

REFERENCES

1. Togias A, Gergen PJ, Liu AH, et al. Rhinoconjunctivitis symptoms in children and adolescents with asthma: Longitudinal clustering analysis. J. Allergy Clin. Immunol. Published online January 2, 2025. DOI: 10.1016/j.jaci.2024.12.1084

2. Yue M, Gaietto k, Han YY, et al. Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth. JAMA. 2025;333(4):307-318. doi:10.1001/jama.2024.22684

3. The nose knows: Nasal swab detects asthma type in kids. University of Pittsburgh. News release. January 2, 2025. https://www.eurekalert.org/news-releases/1069101