WHAT bacteria and allergens can trigger an asthma crisis is known, but now a group of US researchers has discovered why. As they explain on Science Translational Medicine, some bacteria, such as Klebsiella pneumoniae, stimulate the activity of a molecule called oncostatin M, responsible for inflammation and overproduction of mucus. The results of their study pave the way for the possibility of preventing the acute events of the disease, particularly dangerous, with a targeted therapy: an antibody developed to act selectively against oncostatin M, currently tested in mice.
Severe asthma: not a single disease
Asthma is one of the most common chronic diseases on the planet and the most common in children. According to the WHO, 262 million people were affected in 2019 and the condition is believed to be responsible for the deaths of 461,000 of these. Coughing, wheezing, shortness of air, and chest tightness are common symptoms of an asthma crisis, but there can be several triggers. In other words, there is not a single type of asthma: some forms can be well controlled through conventional treatments, while others do not respond at all (not even to steroids). And for these types there are still no therapies.
I study
Hence the importance of the new study. Led by Sarah Headland from Genentech, the researchers analyzed airway biopsies from 57 patients with severe asthma, 28 with mild or moderate asthma, and 16 healthy people after being exposed to lipopolysaccharide (Lps), a molecule that makes up the outer cell membrane of some bacteria. It was found that in samples of patients with severe asthma Lps activates to a greater extent oncostatin M, a molecule involved in immune and inflammatory responses secreted by cells of the immune system, in particular by pulmonary macrophages.
Towards a targeted therapy
Repeating the experiments on different types of human cells in culture, exposed to both Lps and the bacterium Klebsiella pneumoniae, the authors demonstrated that the activation of oncostatin M is the necessary and sufficient factor to drive the overreaction of the immune system and to trigger inflammation and mucus production in severe asthma. The next step was to develop a specific antibody capable of blocking oncostatin M. Thanks to it, scientists have shown that they can prevent the inflammation that triggers the asthma crisis in an animal model. “Overall – they conclude – these results provide a scientific rationale for the clinical development of a target therapy to prevent the progression of asthma”.
Image: Annie Spratt on Unsplash
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