Effect Modification of T2 Inflammation and Sex Impacts Asthma Exacerbation Rates

Trisha Agarwal; Ryan Peterson; Guillermo Jimenez; Zachary Taich; Sunita Sharma; Fernando Holguin; Meghan D. Althoff

doi:10.1016/j.chpulm.2024.100123

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Effect Modification of T2 Inflammation and Sex Impacts Asthma Exacerbation Rates

Journal article

Open access

Peer reviewed

Effect Modification of T2 Inflammation and Sex Impacts Asthma Exacerbation Rates

Trisha Agarwal, Ryan Peterson, Guillermo Jimenez, Zachary Taich, Sunita Sharma, Fernando Holguin and Meghan D. Althoff

CHEST pulmonary, Vol.3(3), 100123

09/2025

DOI: 10.1016/j.chpulm.2024.100123

PMCID: PMC12652403

PMID: 41311812

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Abstract

Prior studies have identified predictors of asthma exacerbations; however, most lack integration of type 2 (T2) inflammatory markers. In a large electronic health record database, what are predictors of asthma exacerbation rates and is there interaction by T2 inflammation, female sex, and obesity? This is a retrospective cohort study using electronic health record data of patients with asthma followed for at least 1 year in the XXHealth system. The primary outcome was asthma exacerbation rate, defined by the prescription of an oral corticosteroid burst. Predictors of interest included T2 high inflammation, defined as absolute eosinophil count (AEC) ≥ 300 cells/μL, BMI, and sex. Predictors of the numbers of exacerbation and prespecified interactions were identified with negative binomial models. A natural cubic spline was used to model the dose response between AEC and exacerbation rate. The cohort included 70,939 patients with asthma; 52% had T2 high inflammation and 62% were female, with 70% of patients being overweight or obese. Individuals with T2 high inflammation had higher adjusted rates of exacerbation (adjusted incidence rate ratio, 1.13; 95% CI, 1.10-1.16). AEC predicted exacerbation frequency in a dose-dependent manner. There was significant effect modification by sex, with women with T2 high inflammation having increased exacerbation rates compared with men with T2 high inflammation. This study finds an increase in exacerbation rate among patients with T2 high inflammation with asthma and shows a dose-dependent response to AEC. This is the first study to find effect modification by sex and T2 status, identifying a group of patients who could potentially benefit from T2-targeted biologic therapy to decrease their exacerbation rate.

Asthma

Obesity

administrative data

eosinophil

exacerbation

female

sex

Details

Title: Subtitle: Effect Modification of T2 Inflammation and Sex Impacts Asthma Exacerbation Rates
Creators: Trisha Agarwal - University of Colorado Anschutz Medical Campus
Ryan Peterson - University of Colorado Anschutz Medical Campus
Guillermo Jimenez - University of California - San Diego School of Medicine
Zachary Taich - West Coast Pulmonary & Sleep Disorder Center, Oxnard, CA
Sunita Sharma - University of Colorado Anschutz Medical Campus
Fernando Holguin - University of Colorado Anschutz Medical Campus
Meghan D. Althoff - University of Colorado Anschutz Medical Campus
Resource Type: Journal article
Publication Details: CHEST pulmonary, Vol.3(3), 100123
DOI: 10.1016/j.chpulm.2024.100123
PMID: 41311812
PMCID: PMC12652403
NLM abbreviation: CHEST Pulm
ISSN: 2949-7892
eISSN: 2949-7892
Publisher: Elsevier Inc
Language: English
Electronic publication date: 11/26/2024
Date published: 09/2025
Academic Unit: Biostatistics; Internal Medicine
Record Identifier: 9984920952602771

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