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Investigations of a combination of atopic status and age of asthma onset identify asthma subphenotypes.

Huashi LiMario CastroLoren C DenlingerSerpil C ErzurumJohn V FahyBenjamin GastonElliot IsraelNizar N JarjourBruce David LevyDavid T MaugerWendy C MooreSally E WenzelJoe ZeinEugene R BleeckerDeborah A MeyersYin ChenXingnan Linull null
Published in: The Journal of asthma : official journal of the Association for the Care of Asthma (2023)
Objective: Subphenotypes of asthma may be determined by age onset and atopic status. We sought to characterize early or late onset atopic asthma with fungal or non-fungal sensitization (AAFS or AANFS) and non-atopic asthma (NAA) in children and adults in the Severe Asthma Research Program (SARP). SARP is an ongoing project involving well-phenotyped patients with mild to severe asthma. Methods: Phenotypic comparisons were performed using Kruskal-Wallis or chi-square test. Genetic association analyses were performed using logistic or linear regression. Results: Airway hyper-responsiveness, total serum IgE levels, and T2 biomarkers showed an increasing trend from NAA to AANFS and then to AAFS. Children and adults with early onset asthma had greater % of AAFS than adults with late onset asthma (46% and 40% vs. 32%; P  < 0.00001). In children, AAFS and AANFS had lower % predicted FEV 1 (86% and 91% vs. 97%) and greater % of patients with severe asthma than NAA (61% and 59% vs. 43%). In adults with early or late onset asthma, NAA had greater % of patients with severe asthma than AANFS and AAFS (61% vs. 40% and 37% or 56% vs. 44% and 49%). The G allele of rs2872507 in GSDMB had higher frequency in AAFS than AANFS and NAA (0.63 vs. 0.55 and 0.55), and associated with earlier age onset and asthma severity. Conclusions: Early or late onset AAFS, AANFS, and NAA have shared and distinct phenotypic characteristics in children and adults. AAFS is a complex disorder involving genetic susceptibility and environmental factors.
Keyphrases
  • late onset
  • early onset
  • chronic obstructive pulmonary disease
  • lung function
  • allergic rhinitis
  • young adults
  • air pollution
  • gene expression
  • dna methylation
  • copy number