Children with asthma who contract respiratory syncytial virus (RSV) may experience more severe illness than children without asthma, based on new data presented at a global conference sponsored by the Respiratory Syncytial Virus Foundation.

Current data show that RSV is the leading cause for hospitalization among children worldwide. Approximately 200,000 deaths in children, mainly infants, worldwide each year, Gina Aloisio, MD, assistant professor of pediatrics and emergency medicine at Baylor College of Medicine, Houston, and colleagues wrote.

Although RSV is known to trigger exacerbations in children with asthma, the mechanism driving this association remains unclear, the authors noted. “More research is needed to understand why children with asthma are so severely affected with RSV infection compared to children without asthma,” Aloisio told Medscape Medical News.

Aloisio and colleagues used lab-grown tissue models (organoids) to examine RSV activity in the upper airways (nasal organoids, HNOs) and lower airways (tracheobronchial organoids, HTBOs). They derived eight matched upper and lower airway organoids from children with and without asthma and infected them with contemporaneous strains of RSV (RSV/A/Ontario and RSV/B/Buenos Aires). The researchers tracked the virus’ activity over an 8-day period, and used a plaque assay to count the virus particles produced. Cell damage or death was measured using lactate dehydrogenase (LDH).

Overall, RSV behaved similarly in both HNOs and HTBOs, with similar patterns of viral replication, for children with and without asthma, although viral titers were lower in HTBOs after one day than in matched HNOs. The cell composition was similar between HTBOs and HNOs, although the HTBO epithelium was thinner and had fewer ciliated cells, which could increase vulnerability to infection, the researchers noted in their abstract.

Organoids derived from children with and without asthma had comparable airway injury based on similar increases in LDH after RSV infection.

However, the virus spread more significantly in tissue from children with asthma and reached the highest level of activity at about 8 days after infection.

“I was very surprised that, despite overall having fewer infectious virions (the active, infectious form of the virus), organoids derived from children with asthma seemed to have more cell death compared to organoids from children without asthma,” Aloisio told Medscape Medical News. The organoids retained a “memory” of whether they were derived from children with or without asthma, she added.

The results were limited by the small sample size, but the takeaway for clinical practice is to be cautious when a child with asthma contracts RSV, as the virus could affect them more severely than a child without asthma, Aloisio said.

“The next step in this research is to analyze the differences in cytokine release between the upper and lower airways from children with and without asthma,” said Aloisio. “From there, our lab will expand to co-culture systems of airway organoids with immune cells,” she said. The researchers have begun this work in healthy individuals without other respiratory conditions, but will expand to those with asthma and other lung diseases, she noted.

New Window on Viral Activity

The study highlighted the concern that RSV infections pose for pediatricians, particularly during fall and winter months because of complications such as asthma exacerbations and bronchiolitis, said Amer Kechli, MD, professor of clinical pediatrics at the Lewis Katz School of Medicine at Temple University, Philadelphia. “Children with asthma face an increased risk of wheezing, severe disease, and hospitalization during RSV infections,” said Kechli, who was not involved in the study.

The finding that early viral replication was lower in organoid models derived from lower airways than from upper airways, was not unexpected, and consistent with the knowledge that viruses initially replicate in the upper airway before moving to the lower airway, Kechli told Medscape Medical News. However, “a significant and unexpected finding was the increased viral titers in children with asthma compared to those without, observed 8 days post-infection, despite similar levels of airway injury,” he said. “This was noteworthy as children with asthma are generally predisposed to more airway damage because of baseline airway inflammation,” he added.

A study limitation was the inability of the organoid models to incorporate all cell types involved in cellular immunity, which could impact RSV particle replication and ability to cause damage, said Kechli. “The models included goblet cells, ciliated cells, and basal stem cells but lack other immune cells that might influence viral replication and lung damage, and it may be helpful to develop methods to enhance organoid models to include a broader range of immune cells for more comprehensive results,” he said.

Overall, the study raises awareness of the increased risk for complications of RSV infection in children with asthma and provides pediatricians with some information on when in the course of an infection lower airway involvement may occur, Kechli said. However, more research is needed on the implications of increased viral titers in children with asthma to determine their contribution to complication risks, he said. In addition, investigating potential preventive and acute treatment strategies based on the study findings could help mitigate RSV complications in children with asthma, Kechli noted.

The study was funded by the Baylor Clinical Research Center via the Baylor College of Medicine Pandemic Threat Technology Center and the Texas Medical Center Genomics Center for Infectious Diseases. The researchers and Kechli disclosed no financial conflicts of interest.