It's estimated that over 262 million people around the world have asthma, a chronic condition in which the airways are inflamed and narrow. It can cause wheezing, shortness of breath, and coughing. The disorder is thought to be underdiagnosed and undertreated, and it led to around 455,000 deaths worldwide in 2019. There are different types of asthma, which can be caused by allergies, infections, or environmental factors like exposure to toxic fumes or smoke. People with a family history of allergic diseases are at higher risk, particularly when their mother is asthmatic. Researchers have now identified epigenetic changes in the airway cells of adults who had asthmatic mothers, which were different compared to those who had non-asthmatic mothers. This study, which was reported in the Proceedings of the National Academy of Sciences may begin to explain why the risk of asthma increases in children when their mothers have asthma.
Epigenetics can alter gene activity without changing the genetic sequence, and studies have indicated that epigenetic markers can be passed down to future generations. Epigenetics may refer to chemical tags like methyl groups that are linked to DNA, or structural alterations that change how accessible a gene may be to cellular machinery, for example. Environmental influences can alter epigenetic tags, including during development.
In this work, researchers were investigating epigenetic changes associated with asthma. They identified four different methylation patterns in the DNA of airway epithelial cells in asthmatic adults who had asthmatic mothers, and those patterns were different from asthmatic adults whose mothers did not have asthma. Those patterns were linked to a reduction in the activity of genes that are related to immune pathways, noted first study author Kevin Magnaye, Ph.D.
The immune pathways implicated in this study are involved in T cell signaling and adaptive immunity, which cells can invoke during infections. Impaired immune responses to pathogens like bacteria and viruses were also identified.
In type 2-low asthma, which is severe, standard corticosteroid treatments that suppress immunity don't work. "This subtype of asthma is particularly difficult to treat," said senior study author Carole Ober, Ph.D., the Blum-Riese Distinguished Service Professor of Human Genetics at the University of Chicago. "Our results suggest that an underlying cause is due to impaired immune responses," which could explain why corticosteroids are ineffective. But this study shows there may be other approaches that could help treat these patients.
The researchers added that this study benefited from a diverse patient sample. The researchers also used adult airway cells for their initial findings, then confirmed their results in another group of kids.
The epigenetic changes are likely to have occurred during pregnancy, though they did not impact people until later in life.
"The fact that these results were replicated in a separate cohort of children supports the notion that these modifications are present long before adulthood," said Ober.
The researchers are now investigating the epigenetic changes, and how they may be leading to an increase in the risk of asthma.