Children hospitalised with severe pneumonia can safely switch from injectable to oral antibiotics once they begin to recover, allowing many to return home sooner and complete treatment outside hospital. This is according to a major international clinical trial led by researchers from City St George's, University of London, UCL Innovative Clinical Trials Unit, and partners across Africa and Europe, with results published today in The Lancet.

In a groundbreaking new study published in Nature Communications, researchers from the University of Colorado Anschutz Linda Crnic Institute for Down Syndrome (Crnic Institute) discovered unique biological processes altered among individuals with Down syndrome who have different sets of co-occurring conditions. The findings mark an important step toward personalized treatment.

Biological differences are linked to co-occurring conditions of Down syndrome

The study is part of the ongoing Human Trisome Project™, one of the largest and most comprehensive studies of people with Down syndrome, including extensive clinical data, multi-omics data sets and the largest biobank for the study of this condition to date. The Crnic Institute team analyzed hundreds of blood samples to identify physiological differences across research participants with Down syndrome who have histories of medical conditions that are more prevalent in this population. They mapped changes in gene expression, protein levels, metabolite abundance and immune cell types across 100 different clinical traits, producing an unprecedented atlas of the processes underlying variable medical complexity in Down syndrome.

“These results decipher for the first time the conserved effects of the extra copy of chromosome 21 versus effects that are unique or exacerbated in people with Down syndrome that have other co-occurring medical conditions,” said Joaquín Espinosa, PhD, executive director of the Crnic Institute, professor of Pharmacology, principal investigator of the Human Trisome Project and senior author of the paper. “We know that no two individuals with Down syndrome are the same from a clinical standpoint, and now we can understand how this uniqueness reflects in their molecular, metabolic and immune profiles.”

“The number of discoveries produced by this analysis is spectacular,” said Micah Donovan, PhD, instructor of Pharmacology and a lead author of the study. “For example, this effort revealed the outsized effects of obesity in Down syndrome, whereby individuals with obesity display strong changes in key hormonal circuits, metabolism and systemic inflammation."

The researchers used advanced computational tools to analyze the enormous volume of biological and clinical data generated through the study. The resulting dataset is expected to support many future investigations into the wide range of health outcomes experienced by people with Down syndrome.

“We found strong biosignatures of immune dysregulation and cardiac stress that persist throughout life in those with a history of specific congenital heart defects,” explained Srija Chilamcherla, MS, another lead author of the study. “These results pave the way toward the development of biomarkers that could help physicians monitor the lifelong effects of medical conditions that occurred earlier in life.”

Family socioeconomic position may be a more important determiner of children’s health than parental behaviors such as smoking, drinking or caffeine consumption, according to a study published July 23^rd in the open access journal PLOS Medicine by Gemma Sharp from the University of Exeter, UK, and colleagues.