ArticleThe Journal of allergy and clinical immunology2021
Unconjugated bilirubin is associated with protection from early-life wheeze and childhood asthma.
Article in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Bilirubin metabolism in early life and respiratory health during preschool age: A combined analysis of two independent birth cohorts.Med (New York, N.Y.) · 2024Pooled it
- Eight weeks of aerobic exercise, but not four, improves insulin sensitivity and cardiovascular performance in young women.Scientific reports · 2025Trial
- Exploratory integrative analysis of infant gut microbiome and metabolome suggests diet- and microbiome-derived metabolites associated with childhood asthma.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- [Pathological roles of lipid metabolism disorders in asthma and related intervention strategies].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Targeted Delivery of Bilirubin to Pulmonary Endothelium Mitigates Paraquat-Induced Lung Injury.International journal of nanomedicine · 2026Article
- Bilirubin - new insights into an old molecule.Biochemia medica · 2025Review
- The association of infant urinary adrenal steroids with the risk of childhood asthma development.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2024Article
- Bilirubin Levels in Infancy and Their Associations with Body Weight, Levels of Iron-Related Parameters and Steroid Hormone Levels.Metabolites · 2024Article
- Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort.The Journal of allergy and clinical immunology · 2024Article
- Revealing polygenic pleiotropy using genetic risk scores for asthma.HGG advances · 2023Article
- Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles.International journal of molecular sciences · 2023Review
- Early-life fecal metabolomics of food allergy.Allergy · 2023Article
- Article
- Biliverdin/Bilirubin Redox Pair Protects Lens Epithelial Cells against Oxidative Stress in Age-Related Cataract by Regulating NF-Oxidative medicine and cellular longevity · 2022Article
- Prenatal and Postnatal Exposure to Ambient Air Pollution and Preschool Asthma in Neonatal Jaundice Infants.Journal of inflammation research · 2022Article
- [The Role of Nrf2 Pathway Activation in Hippocampal Neuron Injury of Neonatal Rats with Bilirubin Encephalopathy].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- Research Progress of Metabolomics in Asthma.Metabolites · 2021Review
Corrections and comments
- Commented on by
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundWheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood.
objectivesWe sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma.
methodsWe conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma.
resultsEighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress-related metabolites. There were no significant associations between metabolites and allergic sensitization.
conclusionsWe identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.