Every breath you take

With every breath you take, the delicate air sacs in your lungs are filled with oxygen.

Each of the 300 million or so sacs in a healthy set of lungs are surrounded by capillaries that facilitate the transfer of the oxygen into the bloodstream.

For this process to occur, the tissue that makes up the lungs must be elastic and flexible, able to be fully inflated with each breath. In someone with idiopathic pulmonary fibrosis (IPF), the thin lacy walls of the air sacs become stiffened and thick with scar tissue, and unable to be filled with air.

People with the condition initially experience shortness of breath. IPF can progress very quickly and, without intervention, is fatal.

“‘Idiopathic’ means unexplained,” says Dr Davis McCarthy, “We use the term when we can’t pinpoint a cause for a condition.”

Davis and his collaborators have recently published a study in Nature Genetics, which they hope will help better understand what goes wrong in IPF, with the potential to further the development of therapies that treat the causes of the disease, as opposed to its symptoms.

Kathleen’s mother, Margaret, was 64 and had only just retired from nursing when she was diagnosed with the condition in 2019.

“Mum loved the water and swam 20-30 laps every day, 7 days a week. She noticed that she was feeling breathless and finding it harder to do.”

For about 12 months, Margaret struggled to get a definitive diagnosis, facing uncertainty and frustration.

“She had a huge number of tests and was misdiagnosed with something else before she was finally told it was IPF,” Kathleen says.

On hearing that her Mum had IPF, Kathleen and her family says that it was not the diagnosis, but rather the prognosis that was the shock.

“Mum was told that she had 5 years at most, and there were no real treatments available. Sadly, she died just 2 and a half years later.”

“The last 6 months of her life were devastating. She spent a huge amount of time in and out of ICU and had very little quality of life. We organised a nurse at home to help her, but towards the end, she had to go into care.”

“Because this was during Covid, and I was living in Melbourne and Mum in Queensland, I sadly didn’t get to introduce her to her new granddaughter before she passed away,” says Kathleen.

Over 1,250 Australians are diagnosed with IPF every year, most of whom are between the ages of 50 and 70 years old.

Davis says that while there are some new treatments that can slow the progress of the disease, the only current effective therapy is lung transplantation, which has limited availability and in which one set of medical problems is swapped for another.

“Our study is the first to examine exactly what is happening in individual cell types in the lung of people affected by the condition,” said SVI’s Dr Davis McCarthy, who co-led the research with his collaborator Dr Nicholas Banovich from the Translational Genomics Research Institute and colleagues at Vanderbilt University Medical Center in the U.S.

“In recent years, it has become clear that genetic factors contribute substantially to a person’s risk of developing IPF, but the exact influence of these genetic variations has not been well understood,” Davis says.

The team sampled lung tissue taken from 116 people, 67 of whom had the lung disease, and examined the genetic factors that influence how genes are turned on and off at a single-cell level, within 38 different individual cell types in the lung.

They showed that there were different factors found either only in healthy lung tissue or only in diseased lung tissue, and that these were highly cell type specific. This suggests that these factors may be important contributors to disease.

The study is the first to use single-cell genomics to study genetic regulation of gene expression in complex, solid, primary human tissues – in this case, the lung – pioneering new methods for identifying genetic causes of disease.

Kathleen reflects of the dire prognosis of IPF, saying, “With the cause still to be identified, it’s not surprising that there are no great treatments. For the treatment of cancer, medical advances have been able to provide some hope. For IPF, there’s no hope.”

With their results, Davis and his team are taking the first steps to provide just that.