An estimated 2.3 million U.S. children and adolescents experienced asthma attacks in 2019, according to the Centers for Disease Control and Prevention. Black and Hispanic children who live in low-income urban environments in the United States are at particularly high risk for asthma that is prone to attacks.
These children often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control.
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In an earlier study, researchers identified multiple networks of functionally related genes that are activated together and are associated with asthma attacks in children and adolescents who live in low-income urban settings. Some of these genetic networks are specifically associated with cells called eosinophils.
Many people with untreated asthma have a high level of eosinophils in the blood and airways. These cells are thought to increase airway inflammation, which in turn leads to tissue damage, making breathing more difficult.
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Mepolizumab, marketed by GlaxoSmithKline as Nucala, is approved by the Food and Drug Administration to treat people ages 6 years and older with eosinophilic asthma and has been shown to reduce blood levels of eosinophils.
The investigators hypothesized that mepolizumab would suppress the eosinophil-specific gene networks associated with asthma attacks in Black and Hispanic urban youth with eosinophilic asthma, thereby reducing the number of asthma attacks in this population.
They further hypothesized that by analyzing asthma-associated gene networks during treatment, they would identify certain networks associated with stronger or weaker responses to mepolizumab. The MUPPITS-2 trial was designed to test these hypotheses.
The MUPPITS-2 study team enrolled 290 children ages 6 to 17 years whose asthma was difficult to control, prone to attacks and characterized by high blood levels of eosinophils. Seventy percent of the participants were Black, 25% were Hispanic, and all lived in low-income neighborhoods in nine U.S. cities.
The children were assigned at random to receive an injection of either mepolizumab or a placebo once every four weeks for 12 months. No one knew who received which type of injection until the end of the trial. All the participants also received asthma care based.
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The study team collected nasal secretions from the children before they began receiving injections and at the end of one year. RNA, a form of genetic material, was extracted from cells in the nasal secretions and was sequenced and analyzed to determine the activity of various gene networks.
The study team also collected blood samples from participants at the start and end of the trial and a few times in-between. Asthma control improved in all study participants, regardless of whether they received mepolizumab or placebo.
This suggests that by participating in the trial, the children benefited from frequent clinic visits and maintained better adherence to hand-held devices called asthma inhalers, which deliver standard medication to the lungs to ease asthma symptoms.
To understand this result and explain why this effect is significantly lower than what has been reported in adults in other studies, the researchers examined activity levels of the networks of genes identified during MUPPITS-1 as associated with asthma attacks.
The findings also identify potential future targets for further reducing asthma attacks among these children and adolescents. Importantly, clearly illustrating how a variety of gene networks associated with airway inflammation play a role in asthma attacks in low-income urban youth, paves the way for using gene activation patterns to monitor new asthma therapies in future clinical trials in this population.
Source: Medindia
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