New Study Maps Early Lung Damage in Children with Cystic Fibrosis

Within 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.

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.

Why look at lung damage in preschoolers?

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."

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.

'Significant study' despite limitations

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.

Of the 37 kids with CF in the study, 12 kids were using modulators for different periods of time, which Dr Schneider-Futschik said made it "difficult to draw firm conclusions about treatment effects".

Also, Dr Schneider-Futschik said the control group of kids without CF wasn't a true group of very healthy kids, with many undergoing procedures for upper airway conditions.

Where to from here

Most newborn babies in Australia are screened for CF, with about one in 2,500 babies born with the condition.

There's no cure for CF but treatments like modulators can help slow the disease's progression.

Ms Milne said Lewis, who is now 12, uses a CFTR modulator and does twice-daily physio exercises to clear his airways and his lungs.

His lung function is currently that of a "normal healthy child", with doctors expecting him to live a long life.

Kids born today with CF can expect to live well into their 60s, Dr Neeland said, with their quality of life significantly better than previous generations.

But she said her study suggested targeted anti-inflammatory treatments alongside current medications could potentially improve outcomes for kids.

It's a theory worth exploring, Dr Schneider-Futschik said.

"We’re already seeing growing interest in starting CFTR modulators very early in life, and even the possibility of treatment in utero," she said.

"If some of these inflammatory and immune abnormalities are beginning before or immediately after birth, studies like this suggest there could be real value in intervening as early as possible to try to prevent that disease process from becoming established at all."