The association of infant urinary adrenal steroids with the risk of childhood asthma development

Kedir N Turi; Yajing Li; Yaomin Xu; Tebeb Gebretsadik; Christian Rosas-Salazar; Derek A Wiggins; Chris McKennan; Dawn Newcomb; James E Gern; Tina V Hartert

doi:10.1016/j.anai.2024.04.008

The association of infant urinary adrenal steroids with the risk of childhood asthma development

Ann Allergy Asthma Immunol. 2024 Apr 15:S1081-1206(24)00215-1. doi: 10.1016/j.anai.2024.04.008. Online ahead of print.

Authors

Affiliations

¹ Department of Epidemiology and Biostatistics, Indiana University, Bloomington, Indiana. Electronic address: knturi@iu.edu.
² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
³ Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁵ Department of Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
⁶ Department of Pediatrics, University of Wisconsin, Madison, Wisconsin.
⁷ Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: tina.hartert@vumc.org.

PMID: 38631429
DOI: 10.1016/j.anai.2024.04.008

Abstract

Background: Adrenal steroids play important roles in early-life development. However, our understanding of the effects of perinatal adrenal steroids on the development of childhood asthma is incomplete.

Objective: To evaluate the associations between early-life adrenal steroid levels and childhood asthma.

Methods: Participants included the Infant Susceptibility to Pulmonary Infections and Asthma following Respiratory Syncytial Virus Exposure birth cohort children with untargeted urinary metabolomics data measured during early infancy (n = 264) and nasal immune mediator data measured concurrently at age 2 to 6 months (n = 76). A total of 11 adrenal steroid compounds were identified using untargeted metabolomics and 6 asthma-relevant nasal immune mediators from multiplex assays were a priori selected. Current asthma at ages 5 and 6 years was ascertained using validated questionnaires. Associations were tested using logistic and linear regression with confounders adjustment.

Results: Pregnenetriol disulfate (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.06-0.68) and 3a,21-dihydroxy-5b-pregnane-11,20-dione-21-glucuronide (aOR = 0.34, 95% CI = 0.14-0.75) were inversely associated with childhood asthma at 5 and 6 years after multiple testing adjustment. There was a significant interaction effect of pregnanediol-3-glucuronide by biological sex assigned at birth (aOR = 0.11, 95% CI = 0.02-0.51, for those with female sex) on childhood asthma. Pregnenetriol disulfate was inversely associated with granulocyte-macrophage colony-stimulating factor (β = -0.45, q-value = 0.05). 3a,21-dihydroxy-5b-pregnane-11,20-dione 21-glucuronide was inversely associated with interleukin [IL]-4 (β = -0.29, q-value = 0.02), IL-5 (β = -0.35, q-value = 0.006), IL-13 (β = -0.26, q-value = 0.02), granulocyte-macrophage colony-stimulating factor (β = -0.35, q-value = 0.006), and fibroblast growth factor-β (β = -0.24, q-value = 0.01) after multiple testing adjustment.

Conclusion: The inverse association between adrenal steroids downstream of progesterone and 17-hydroxypregnenolone and the odds of childhood asthma and nasopharyngeal type 2 immune biomarkers suggest that increased early-life adrenal steroids may suppress type 2 inflammation and protect against the development of childhood asthma.