“Asthma exacts a heavy toll, especially on disadvantaged school-aged children of color who live in urban areas,” said Anthony S. Fauci, MD, in a recent news release by the National Institutes of Health (NIH). The NIH recently completed a clinical trial for asthma in this population—a population that has been previously underrepresented in asthma therapeutic trials—to test drug efficacy and advance our understanding of genetic changes underlying this condition.
During an asthma attack, chronic inflammation of the airway leads to swelling of the airway lining, airway muscle contraction, and increased mucus production, significantly reducing the volume of air going through the lungs. An earlier study in Nature Immunology showed genetic networks associated with asthma attacks in children, where some of the activated genes were associated with eosinophils, which are thought to increase airway inflammation.
The NIH clinical trial involved 290 participants who were Black and Hispanic children aged 6–17 years living in low-income neighborhoods in the US. The participants were assigned at random to be injected with either a placebo or a monoclonal antibody called mepolizumab, donated by GlaxoSmithKline. Nasal secretions and blood samples were also collected.
After a year, compared to placebo, mepolizumab safely and significantly reduced blood levels of eosinophils and led to a 27 percent decrease in the rate of asthma attacks in the study population. Transcriptomics analysis revealed that mepolizumab decreased the activity of three eosinophil-related gene networks. However, the drug had no effect on five gene networks related to tissue inflammation and one gene network related to eosinophil activation and mucus overproduction, which may help explain why the drug had a modest efficacy for reducing asthma attacks in this population while also identifying potential future therapeutic targets.