Early lung damage patterns uncovered in children with cystic fibrosis

Researchers have mapped how lung damage begins early in life for children with cystic fibrosis, providing new insights that will help reshape future care.

The research team, led by Murdoch Children's Research Institute (MCRI) and the Peter MacCallum Cancer Centre, has created the largest-ever lung atlas of the lower airways in young cystic fibrosis patients, offering new clues into preventing long-term disease.

MCRI Associate Professor Melanie Neeland said the findings showed that immune abnormalities in cystic fibrosis patients were already well established by early childhood, with current treatments failing to protect the lungs from irreversible damage.

The team analyzed more than 190,000 individual cells from 45 lung samples taken from 37 children treated at The Royal Children's Hospital (RCH) for cystic fibrosis, aged five months to six years. Using advanced single-cell sequencing and protein analysis, they identified 43 distinct types of immune and epithelial cells, building a detailed cellular map of the developing lung.

The research was supported by the Chan Zuckerberg Initiative, reflecting their interest in studying how cells operate to better understand why disease happens and how to correct it.

Published in Mucosal Immunology, the study found that even in preschool-aged children with cystic fibrosis, their key immune cells, especially macrophages, aren't strong enough to help fight off infections. These cells displayed abnormal activity in several important biological pathways, including those involved in inflammation, cholesterol regulation and tissue scarring linked to lung fibrosis.

Importantly, these abnormalities were more pronounced in children who had already begun developing bronchiectasis, a form of irreversible lung damage that can lead to lifelong breathing problems.

Children with cystic fibrosis often face persistent lung infections due to thick mucus in their airways. In Australia, about 1,600 children have cystic fibrosis with one baby born with the condition every four days.

The researchers also examined the effects of commonly used cystic fibrosis medications that focus on the condition's underlying genetic defect.

Associate Professor Neeland said despite major advances in treating cystic fibrosis, the findings suggested that targeted anti‑inflammatory treatments may be necessary alongside current medications to prevent permanent lung damage.

"We discovered immune dysfunction in the lungs begins in the preschool years and persists despite current breakthrough therapies," she said.

"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 "

"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. It also highlights the importance of studying lung disease in preschool children, who are often overlooked in research that focuses on adults."

Shivanthan Shanthikumar, Associate Professor, MCRI, Pediatric Respiratory Specialist at the RCH

Lewis, 12, who has cystic fibrosis, has previously participated in MCRI trials with one transforming how early life lung disease in cystic fibrosis is viewed.

Mum Justine said the cystic fibrosis research had been transformative and encouraged other families to enrol in clinical trials. To help find new treatments, MCRI researchers have also grown human lung stem cell models in the lab to screen thousands of existing medicines to see if any might be effective against cystic fibrosis. 

"We have taken part in research before and would do it again in a heartbeat if it helps other children," Justine said. "The only reason Lewis has access to life-changing medications is because a team of researchers somewhere proved that they work.

"We were encouraged early on by his doctors to not keep Lewis in a bubble, so with the help of different treatments, he can still play sport and thrive in outdoor activities."

Researchers from the University of Melbourne, The Royal Children's Hospital, Walter and Eliza Hall Institute of Medical Research, Garvan Institute of Medical Research and the University of New South Wales also contributed to the research.