Severe type 2 asthma linked to subtle changes of structures within the brain

Research presented at the recent European Respiratory Society Congress in Barcelona, Spain, suggests inflammation driving a severe form of asthma may extend beyond the lungs to affect the brain's white matter and grey matter regions

People living with a severe form of asthma show subtle differences in the structure of their brains compared with people whose asthma is well controlled, according to novel research presented at the European Respiratory Society (ERS) Congress in Barcelona, Spain.

The study, led by researchers from the UK’s National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Bristol (BRC: Bristol) and City St George's University of London, UK, suggests that the inflammation driving severe asthma may affect more than the lungs. Dr George Nava, an NIHR Academic Clinical Lecturer in the Bristol Academic Respiratory Unit presented the findings.

Previous studies have suggested that asthma may be associated with changes in the brain but little has been known about whether these changes were more pronounced in people with severe disease. Severe type‑2 asthma is caused by an overactive immune response. It causes persistent inflammation, frequent asthma attacks and difficulty to breathe. Many patients require multiple medications and some remain difficult to treat despite intensive therapy.

“Asthma is usually thought of as a disease of the lungs but growing evidence suggests its effects may extend well beyond the airways.

“We wanted to investigate whether people with severe type‑2 asthma show more differences in brain structure compared to those [in whom] asthma is well controlled,” Nava told the Congress.

To investigate this question the researchers recruited 50 people with severe type‑2 asthma and compared them with 25 people with well‑controlled mild or moderate type‑2 asthma. Participants underwent magnetic resonance imaging using a state‑of‑the‑art technique called quasi‑diffusion imaging which can reveal the microscopic structure of white matter pathways in the brain.

White matter acts as the brain’s communication network, connecting different regions and helping information to travel efficiently around the brain.

The researchers found changes in both the size of specific brain regions and in the organisation of the brain’s white matter network, which is responsible for carrying signals between different parts of the brain. People with severe asthma had less‑organised white matter than those with well‑controlled asthma.

The team also identified differences in the size of specific structures such as the hippocampus and brain regions such as the temporal lobes. Importantly, the degree of white matter change was linked to levels of type‑2 inflammation which suggests a possible connection between the inflammation associated with severe asthma and changes in the brain.

“We found measurable differences in brain structure in people with severe type‑2 high asthma compared with people whose asthma was mild‑moderate and well controlled.

“Across all participants, higher levels of type‑2 inflammation were associated with greater differences in brain white matter. While this study cannot prove that inflammation causes these changes, it does suggest there may be a biological link that deserves further investigation,” Nava explained.

The researchers are now investigating whether these differences change once patients begin treatments that target the inflammation driving severe type‑2 asthma.

“One of the most important questions is whether these brain changes can be prevented or reversed. We hope our ongoing work will help to answer that,” said Professor James Dodd, professor of respiratory medicine at the University of Bristol and chief investigator for the study.

At the congress Professor Apostolos Bossios, Head of the European Respiratory Society’s Assembly on airway diseases, asthma, COPD and chronic cough but was not involved in the research, commented:

“We already know that asthma can have effects beyond the lungs, including impacts on memory, thinking and wellbeing. Type 2 asthma is the most common asthma phenotype. Approximately 5 to 10 per cent of patients develop severe disease, characterised by persistent symptoms, frequent exacerbations and ongoing inflammation despite high‑intensity treatment, leading to impaired lung function, reduced quality of life and poor asthma control.

“This study suggests that inflammation in severe type‑2 asthma is not limited to the lungs but is also seen in the brain and is more severe than in patients with mild‑to‑moderate, well‑controlled asthma. The chronic inflammation associated with asthma can negatively affect brain health. To study how this inflammation is linked to changes elsewhere in the body could help us to understand the wider impact of the disease and to determine whether these changes can be prevented or reversed with treatment,” he concluded.

For further information please visit: www.ersnet.org/congress