Mechanism Behind Hyperresponsiveness During Asthma – Discovered

Asthma is one of the most common major non-communicable diseases in which the airways are narrowed due to the production of extra mucus. This is characterized by breathing difficulty, coughing, a whistling sound (wheezing), and shortness of breath. Asthma also allows the airways to become hyperresponsive (overreactive) to various types of stimuli, such as cold air, physical exertion, and chemicals. A new mechanism that contributes to, and explains, airway hyperresponsiveness is found by the researchers from Uppsala University, published in the scientific journal Allergy.

Asthma is said to impact 300 million people globally. The global asthma treatment market size stood at over $18 billion US in 2019. It is commonly diagnosed using a "methacholine test" that helps determine whether a person is showing signs of airway hyperresponsiveness.

Methacholine binds to muscarinic receptors in the smooth muscle cells lining the inside of the trachea. These muscle cells then begin to contract, causing constriction of the trachea.

Hyperresponsiveness Mechanism During Asthma

To find the airway hyperresponsiveness induced by methacholine, the study team utilized a mouse model of asthma, where the mice were made allergic to house dust mites. It was found that the “mast cells” contribute to airway hyperresponsiveness by having a receptor that recognizes methacholine: muscarinic receptor-3 (M3).

When methacholine binds M3, the mast cells release serotonin. This then acts on nerve cells, which in turn control the airways. Thereafter, the airways produce acetylcholine, which also acts on M3 in smooth muscle cells and makes the trachea contract even more. A vicious cycle is underway.

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Mast cells are a type of immune cell that belongs to the innate immune system. They are found mainly in tissues that are in contact with the external environment, such as the airways and the skin, and react quickly to foreign substances, therefore playing a major part in the body's defense against pathogens.

The discovery demonstrates the efficacy of existing drugs like tiotropium, that was previously thought to work solely by blocking M3 in smooth muscle. Thus the drugs are probably also efficacious because they prevent activation through M3 in mast cells.

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Also, the study brings to light the role of mast cells in rapidly releasing the serotonin in response to various stimuli, which contributes to airway hyperresponsiveness – long underestimated action.

Source-Medindia