Urinary eicosanoid levels in early life and risk of atopic disease in childhood - 28/06/24

Doi : 10.1016/j.jaci.2024.05.022

Liang Chen, MSc ^a,^c, Nicklas Brustad, MD, PhD ^a, Min Kim, MSc, PhD ^a,^b, Yang Luo, MSc ^a, Tingting Wang, MSc, PhD ^a, Mina Ali, MSc, PhD ^a, Nicole Prince, BSc, PhD ^c, Yulu Chen, BSc, PhD ^c, Su Chu, MD, PhD ^c, Sofina Begum, BSc, PhD ^c, Kevin Mendez, BSc, PhD ^c, Rachel S. Kelly, BSc, PhD ^c, Ann-Marie Schoos, MD, PhD ^a,^d, Morten A. Rasmussen, MSc, PhD ^a,^e, Javier Zurita, MSc, PhD ^f,^g, Johan Kolmert, MSc, PhD ^f,^g, Jakob Stokholm, MD, PhD ^a,^d,^e, Augusto Litonjua, MD, MPH ^h, Scott T. Weiss, MD, MS ^c, Klaus Bønnelykke, MD, PhD ^a, Craig E. Wheelock, MSc, PhD ^f,^g,^{^{∗
Co-senior authors.}}, Jessica Lasky-Su, ScD ^c,^{^{∗
Co-senior authors.}}, Bo Chawes, MD, PhD, DMSc ^a,^⁎^{^{∗
Co-senior authors.}}
^a Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
^b Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
^c Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
^d Department of Pediatrics, Slagelse Hospital, Slagelse, Denmark
^e Section of Microbiology and Fermentation, Department of Food Science, University of Copenhagen, Slagelse, Denmark
^f Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
^g Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
^h Division of Pediatric Pulmonary Medicine, Golisano Children’s Hospital, University of Rochester Medical Center, Rochester, NY

^∗Corresponding author: Bo Chawes, MD, PhD, DMSc, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.Copenhagen Prospective Studies on Asthma in ChildhoodHerlev and Gentofte HospitalUniversity of CopenhagenCopenhagenDenmark

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Abstract

Background

Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs), and leukotrienes with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. This study aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease.

Methods

This study quantified the levels of 21 eicosanoids in urine from children from the COPSAC₂₀₁₀ (Copenhagen Prospective Studies on Asthma in Childhood 2010) (age 1 year, n = 450) and VDAART (Vitamin D Antenatal Asthma Reduction Trial) (age 3 years, n = 575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of type-2 inflammation, applying false discovery rate of 5% (FDR5%) multiple testing correction.

Results

In both cohorts, analyses adjusted for environmental determinants showed that higher TXA₂ eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P < FDR5%) and type-2 inflammation (P < .05). In VDAART, lower PGE₂ and PGI₂ eicosanoids and higher isoprostanes were also associated with increased risk of atopic dermatitis (P < FDR5%). For wheeze/asthma, analyses in COPSAC₂₀₁₀ showed that lower isoprostanes and PGF₂ eicosanoids and higher PGD₂ eicosanoids at age 1 year associated with an increased risk at age 1-10 years (P < .05), whereas analyses in VDAART showed that lower PGE₂ and higher TXA₂ eicosanoids at age 3 years associated with an increased risk at 6 years (P < FDR5%).

Conclusions

This study suggests that early life perturbations in the eicosanoid metabolism are present before the onset of atopic disease in childhood, which provides pathophysiological insight in the inception of atopic diseases.

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Key words : Atopic dermatitis, eicosanoids, COPSAC, VDAART, childhood asthma, type-2 inflammation

Abbreviations used : AD, c-TXA₂s, FDR5%, Feno, IsoPs, LTE₄, LTs, PCA, PGs, PGD₂, TXs, TXA₂