A research team, led by Murdoch Children’s Research Institute (MCRI) in Parkville, Australia, and the Peter MacCallum Cancer Centre in Melbourne, has developed the largest lung map of the lower airways in pediatric patients with cystic fibrosis (CF). The model offers new insights into treating the condition and preventing progressive damage.
The research findings are detailed in the paper, “Single-Cell Profiling of BAL in Preschool Cystic Fibrosis Reveals Macrophage Dysregulation and Ivacaftor-Modified Inflammatory Programs in the Early Life Lung,” published in Mucosal Immunology.
Melanie Neeland, PhDMCRI
“We discovered immune dysfunction in the lungs begins in the preschool years and persists despite current breakthrough therapies,” Dr. Neeland said in a MCRI news release.
The study included 45 lung samples taken from 37 children with CF, aged five months to six years, who were treated at The Royal Children’s Hospital (RCH). The researchers used advanced single-cell sequencing and protein analysis to examine more than 190,000 individual cells. After identifying 43 distinct types of immune and epithelial cells, the team created a comprehensive cellular map of a developing lung.
In children as young as preschool-aged who have CF, their primary immune cells, especially macrophages, aren’t mature enough to fight off infection. The analyzed cells showed abnormal activity in critical biological pathways, including inflammation, tissue scarring and cholesterol regulation. The abnormalities were more prominent in kids who also had bronchiectasis.
The researchers evaluated common medications used to treat the underlying genetic defect of CF and found children with the condition may also require targeted anti-inflammatory medications to reduce long-term lung damage.
“Although these therapies have been considered highly effective treatments, our findings in children suggest their impact on lung disease may not be as good as once predicted,” Dr. Neeland said. “This suggests that early intervention strategies that combine these medications with targeted anti-inflammatory therapies could help prevent lung damage. These findings provide a powerful new resource, highlighting a critical window for intervention.”
“The study shows there’s still a long way to go to ensure people with cystic fibrosis can live unaffected by the disease,” said Shivanthan Shanthikumar, MD, associate professor at MCRI and pediatric respiratory specialist at the RCH. “It also highlights the importance of studying lung disease in preschool children, who are often overlooked in research that focuses on adults.”
