Severe Asthma Tied to Changes in Brain's White Matter

People living with severe asthma have slightly different brain structure than people whose asthma is well controlled, according to new research presented today at the European Respiratory Society Congress in Barcelona. The study is the first to link the severity of inflammation in asthma to measurable differences in brain structure, and it was led by the NIHR Biomedical Research Centre in Bristol and City St George’s, University of London, in the United Kingdom.

Earlier research had already hinted that asthma might be linked to changes in the brain, but it was unclear whether those changes were more pronounced in severe forms of the disease. Severe type 2 asthma results from an overactive immune response, driving persistent inflammation, frequent attacks and breathing problems, and some patients respond poorly to treatment even on multiple medications at once.

The scans covered 50 people with severe type 2 asthma and 25 people with mild to moderate type 2 asthma that was well controlled. Researchers used MRI with a technique known as quasi-diffusion imaging, which reveals the microscopic structure of white matter pathways, the network that connects different parts of the brain and carries signals between them.

In the group with severe asthma, white matter was less organized than in the group whose disease was under control. The researchers also found differences in hippocampal size and in the structure of the temporal lobes. The higher the level of type 2 inflammation, the greater the differences in white matter, pointing to a possible link between inflammation in severe asthma and changes in the brain.

The findings were presented by Dr. George Nava, a clinical lecturer at the Bristol Academic Respiratory Unit. He explained why the team set out to do this research.

“Asthma is usually thought of as a disease of the lungs, but a growing body of evidence suggests its effects may reach well beyond the airways. We found measurable differences in brain structure in people with severe type 2 asthma compared with people whose asthma was mild to moderate and well controlled.”

Nava also added a caveat about causation.

“This study doesn’t prove that inflammation causes these changes, but it points to a possible biological link that deserves further investigation.”

The team is now examining whether these differences change once patients start treatment aimed at the inflammation that drives severe type 2 asthma. Lead investigator Professor James Dodd, of the University of Bristol, said that is a key question for the next stage of the work.

“One of the most important questions is whether these changes in the brain can be prevented or reversed. We hope our further work will help answer that.”

Commenting on the research, Professor Apostolos Bossios, chair of the European Respiratory Society’s group on airway diseases, asthma, chronic obstructive pulmonary disease and chronic cough, and associate professor of respiratory medicine at the Karolinska Institute in Sweden, who was not involved in the study, said:

“About 5 to 10 percent of patients develop a severe form of the disease, characterized by persistent symptoms, frequent flare-ups and inflammation that doesn’t let up.”

According to figures cited by the European Respiratory Society, that same range, between 5 and 10 percent of people with asthma, develop this more severe form of the disease, marked by constant symptoms and inflammation that does not subside even with intensive treatment.

The research, presented at the Barcelona congress, has clear limits. It does not prove that inflammation causes the changes in the brain, only that the changes are associated with its level. It is also not known whether the differences observed in white matter, the hippocampus and the temporal lobes can be prevented or reversed with treatment, a question the Bristol team is preparing to address in the next phase of its work.