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. 2025 Feb;155(2):547-556.
doi: 10.1016/j.jaci.2024.08.031. Epub 2024 Sep 20.

Clinical and molecular analysis of longitudinal rhinitis phenotypes in an urban birth cohort

Sima K Ramratnam  1 , Molly Johnson  2 , Cynthia M Visness  2 , Agustin Calatroni  2 , Mathew C Altman  3 , Tomasz Janczyk  3 , Kathryn E McCauley  4 , Claire Schachtschneider  4 , Kei E Fujimura  4 , Douglas W Fadrosh  4 , Susan V Lynch  4 , Leonard B Bacharier  5 , George T O'Connor  6 , Megan T Sandel  6 , Meyer Kattan  7 , Robert A Wood  8 , Peter J Gergen  9 , Daniel J Jackson  10 , Alkis Togias  9 , James E Gern  10 ; Childhood Asthma in Urban Settings (CAUSE) Network
Affiliations

Clinical and molecular analysis of longitudinal rhinitis phenotypes in an urban birth cohort

Sima K Ramratnam et al. J Allergy Clin Immunol. 2025 Feb.

Abstract

Background: Chronic rhinitis symptoms cause significant health burden among children and can have a heterogeneous presentation. Defining phenotypes of childhood chronic rhinitis and associated pathobiology may lead to prevention or improved treatments.

Objectives: We sought to identify longitudinal patterns of rhinitis symptoms in childhood and determine their associations with early life risk factors, allergic comorbidities, and nasal epithelial cell gene expression.

Methods: Chronic rhinitis symptoms were evaluated from ages 1 through 11 years in 485 urban children at high risk for allergic disease in the URECA (Urban Environment and Childhood Asthma) birth cohort. We identified longitudinal rhinitis phenotypes and their relationships to early life exposures, atopic comorbidities, and patterns of nasal epithelial gene expression at age 11 years.

Results: Chronic rhinitis symptoms started early in many children and were a risk factor for developing aeroallergen sensitization. We identified 4 longitudinal rhinitis phenotypes: low/minimal, persistent, persistent decreasing, and late increasing. Persistent rhinitis was most closely linked to allergic sensitization and asthma. Risk factors for persistent rhinitis included frequent colds (P < .001), antibiotic use (P < .001), and reduced exposure to common indoor aeroallergens (P = .003). Compared to low/minimal rhinitis phenotype, the other rhinitis phenotypes were associated with increased expression of canonical type 2 genes and decreased expression of immune response genes.

Conclusions: In urban children, rhinitis symptoms often precede aeroallergen sensitization. Rhinitis phenotypes based on symptoms had distinct risk factors and nasal transcriptome. These results suggest that focusing on early life risk factors and distinct immune mechanisms may be a target to preventing chronic rhinitis in childhood.

Keywords: Chronic rhinitis; allergic sensitization; endotypes; environmental exposures; hay fever; phenotypes; seasonal rhinitis; transcriptomics.

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Conflict of interest statement

Disclosure statement This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health under awards 1UM1AI114271-01, UM2AI117870, 1U01AI178772, and AI160040. Additional support was provided by the National Center for Research Resources, National Institutes of Health under grants NCRR UL1TR001079, 1UL1TR001430, UL1TR001873, and UL1TR002345. Disclosure of potential conflict of interest: S. V. Lynch is a board member and consultant with Siolta Therapeutics Inc. The rest of the authors declare that they have no relevant conflicts of interest. Disclaimer: Drs Gergen's and Togias' coauthorship of this report does not constitute official endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, or any other agency of the US government.

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