'Lung atlas' maps changes to immune cells of kids with cystic fibrosis

Lewis took part in the research project when he was a preschooler. (Supplied: Justine Milne) Australian researchers analysed 190,000 individual cells from 37 kids with cystic fibrosis, building a "lung atlas" of cells in the lower airways of children with the condition. The study found young kids with CF had changes in their immune system that were linked to lung damage at an early age. Researchers said the study suggested targeted anti-inflammatory treatments could improve outcomes for kids with CF, if used alongside current medications. Link copiedShareShare articleWithin 24 hours of being born, Lewis Milne needed emergency surgery to remove a blockage in his small intestine. This type of blockage, called meconium ileus, can be the first sign of cystic fibrosis. Still, Lewis's diagnosis came as a "huge shock" to his mum Justine Milne, who said the family was completely unprepared and unaware of the possibility before he was born. "It was just so overwhelming," Ms Milne said. Lewis Milne grew into a happy kid who loves animals and being outdoors. (Supplied: Justine Milne) Cystic fibrosis (CF) is an inherited, progressive genetic disease caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In a healthy body, the CFTR protein helps balance salt and water in the body's organs. But in a body with CF, the CFTR protein doesn't work properly and thick, sticky mucus develops in the lungs and digestive system, leading to frequent infections and digestive problems. In an effort to help researchers understand the condition in its early stages, Lewis's family signed him up as a preschooler to take part in a recently published study, which mapped out early lung damage in kids with CF. Lead author Melanie Neeland, a senior research fellow at Murdoch Children’s Research Institute (MCRI), said most CF research to date looked at older children and adults with more advanced disease. Dr Neeland said it was critical researchers learnt more about the early stages of CF lung disease because irreversible structural damage began during infancy and early childhood. By understanding more about was happening in childhood doctors could potentially stop this damage from starting. The researchers analysed the genetic profile of 190,000 individual cells from 37 kids with CF and eight children without the condition, building what they called a "lung atlas" of the lower airways in young kids with CF. "We created a map of cells in the lungs of young children with cystic fibrosis," Dr Neeland said. "We found that even in this early age, that in the preschool years, the immune system in the lungs is already abnormal in children with CF and we found this was linked to early lung damage." Cystic fibrosis is a genetic disease which affects the lungs, pancreas and other organs. (Unsplash: Robina Weermeijer) The researchers observed changes in immune cells called macrophages — white blood cells that act as the body's first line of defence against infection — showing these cells were not functioning properly. A small number of the children in the study used a treatment option known as CFTR modulators, which help improve the function of the CFTR protein. The researchers compared the lung cells of the CF kids using CFTR modulators with cells from the group of kids without CF. They found that even after starting treatment with modulators, the lungs of kids with CF were more prone to inflammation. Dr Neeland said this observation suggested that modulators alone weren't doing enough to protect the lungs of young kids, and that anti-inflammatory treatments might also be needed. As CF is a progressive disease, earlier treatment could prevent long-term lung damage, she said. Since the study was undertaken, a new generation of modulators has been approved for use in Australian children, but Dr Neeland suggested the results seen in this study would be relevant to the newer treatments based on studies conducted on adults. Elena Schneider-Futschik, a clinical researcher at the University of Melbourne who did not contribute to the study, described the research as "significant". "The study adds to growing evidence that CF lung disease isn't just about mucus and infection, it's also about early immune dysregulation that may contribute to irreversible lung damage over time," she said. However, Dr Schneider-Futschik noted that there were some limitations to the study itself. Firstly, she pointed out that the study involved just 45 kids. But she noted this small cohort wasn't surprising considering how "invasive and ethically challenging" it was to collect lung samples from preschool children, especially in healthy kids. "This type of research is extremely difficult to perform," she said. It can be challenging to find healthy volunteers for a study like this, which can be invasive. (Unsplash: Bermix Studio) Of the 37 kids with CF in the study, 12 kids were using modula

'Lung atlas' maps changes to immune cells of kids with cystic fibrosis

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