Asthma is a chronic condition that is characterized by difficulty breathing, coughing, and wheezing which is caused, in part, when the affected individuals’ airways narrow, swell, and produce extra mucus. Asthma was once thought to be a single disease, but now it is well known that it is a spectrum of diseases with genetics and a multitude of environmental factors (e.g. viral or bacterial infections) contributing to the development and progression of the disease. According to the Asthma and Allergy Foundation of America, approximately 25 million Americans are currently living with asthma. And while the amount of asthma attacks decreased during the COVID-19 pandemic, the prevalence of asthma among the general population has remained stable for years.
Currently there is no cure for asthma, but treatment can be effective in many instances. However, in cases of severe asthma, a subset of individuals fails to respond to treatment. A recent study, published in the journal Science Translational Medicine, discovered that a certain protein is involved in the process of mucus hypersecretion during a bacterial infection, and as such, may be a key target to help treat severe asthma.
The lungs were previously considered a sterile organ. Currently, however, it is well established that the mucus membrane of the lungs contains its own microbiome – or a rich microbial population in the respiratory tract that contains a complex variety of bacteria, fungi, and other microorganisms. A proper maintenance of the lung microbiome appears to be critical for good health and healthy lung function. Indeed, in diseases such as asthma, the lung microbiome becomes dysregulated leading to bacterial dysbiosis and an increase in severe asthma. For the current study the researchers were interested in the mechanisms that lead to lung bacterial dysbiosis in patients with severe asthma.
In the study, the researchers found that a protein called oncostatin M (OSM) was elevated in human lung biopsies from patients with asthma. Following this finding, the researchers asked whether OSM could be mediator that contributes to bacterial dysbiosis in severe asthma. In their systematic study, the researchers induced a bacterial infection in experimental mice and found that the mice also showed elevated OSM in lung tissue, and a significant increase in airway mucus production. Then, the researchers developed two important tools for their research: a genetic knockout mouse of OSM which was incapable of producing the OSM protein, and an antibody against OSM that could prevent its effects. Using these tools, they found that airway mucus hypersecretion was dependent on the OSM protein after bacterial exposure, such that inhibiting OSM prevented bacterial-associated mucus production.
Overall, the researchers found that blocking OSM reduced severe asthma-related symptoms. Additionally, they have identified that OSM may be a druggable target for the treatment of severe asthma.
Sources: American Lung Association; Asthma and Allergy Foundation of America; Labroots; CDC; Science;nature