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New Study Discovers Why Airways Shut Down during Asthma Attacks

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Asthma is a debilitating disorder of the respiratory system, leading the person to experience breathing difficulties, chest pain, and the inability to speak or ask for help. An approximate 300 million people in the world suffer from asthma, about 25 million in the United States and 5.4 million in the United Kingdom. Scientists know that a protein found in epithelial cells can cause asthma, but they do not how it works until the researchers from Houston Methodist Research Institute discovered the secret mechanism.

Mucin is a protein produced by dedicated cells within epithelial cells and tissues that can form gel-like secretions in the body. The protein is important to keep the epithelial tissues moisturized and healthy, and maintain the surface of the airways in the lungs. Without mucin, the epithelial tissues in the lungs will become dry that can cause irritation, which leads to respiratory complications.

In a 2006 study, mucin has been observed in a number of chronic inflammatory lung diseases. The researchers noted that overproduction and hypersecretion of the protein can be stimulated by several mediators, such as irritants and infection. They also found that overexpression of mucin in the airways is common among patients with bronchial asthma, chronic obstructive pulmonary disease or COPD, bronchiectasis, and cystic fibrosis.

While previous studies are left with the mucin mystery, the researchers at Houston Methodist found a new explanation of what causes the airways to close when asthma attacks. The discovery may change the lives of millions with the new types of asthma medications related to the findings.

Asthma normally occurs when the lung’s airways are irritated by biological or environmental factors, such as allergy or chemicals. The irritation will trigger the protein to produce mucus in order to protect the airways, but the overproduction of the sticky, gel-like substance clogs the airways that prevent the air to travel in and out. The result is shortness of breath on the person.

The researchers discovered two molecules in the airways that can be influenced to solve the problem of overproduction. They identified the association of another protein called interleukin 9 or IL9 with mucin-producing cells. IL9 protein is used by the T helper cells, a type of white blood cells responsible for the adaptive immune response. In adaptive immunity, the T helper cells help activate B cells to produce antibodies, command macrophages to destroy devoured microbes, and induce cytotoxic T cells to kill infected cells. In a normal scenario, T helper cells use IL9 to alert the immune system against foreign toxins.

However, T helper cells are hyperactive during asthma episodes and they express the second molecule, the OX40. The second molecule organizes certain regions of DNA called super-enhancers which determine what genes should be active. The process helps the immune cells survive longer, but triggers the T helper cells to produce a large amount of IL-9, which results in the massive production of mucus in the airways.

“Embedded in these epithelial cells are a very important cell type called mucin-producing cells that are vital for keeping the epithelial surface moisturized and healthy, and they secrete mucin to protect the surface of the airways. Production of mucin is normally tightly controlled, but too much of it can be damaging,” said Dr. Xian C. Li from the Immunobiology and Transplant Science Center at the Houston Methodist Research Institute.

The OX40 practically manages the IL-9 production and in effect, the secretion of mucin. Dr. Li said that specific chemical inhibitors that can prevent IL-9 may pave way for new drugs to treat asthma, which may be more effective and safer than steroids.

Steroids are one of many medications designed to reduce inflammation, swelling, and overproduction of mucus in the airways, which relieve symptoms of asthma. Steroid medications are sold in different forms including inhalers and nebulizers. But the use of steroids can cause potential health risks to the patient, such as:

- Thrush or yeast infection in the mouth characterized by white creamy lesions that can spread to the gums and tonsils.

- A sore mouth or throat.

- A cough or throat irritation.

- Croaky or hoarse voice or dysphonia.

- Nosebleeds.

- Contact hypersensitivity due to allergic contact dermatitis. It is an allergic reaction characterized by lesions similar to eczema around the lips and nose, caused by the aerosolized particles.

- Bruising that may be caused by the thinning of the skin from chronic use of steroids.

- Pneumonia has been considered but remains under debate. The association of this lung condition is about the effects of steroids on the immune system. Steroids diminish the strength of the immune system, making the lungs vulnerable to infection.

Taking steroid inhalers for long periods can cause side effects associated with steroid tablets, such as difficulty in sleeping, changes in mood, and increase in appetite.  

[메디컬리포트=Ralph Chen 기자]

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