Airway discovery may result in new treatment

Researchers from the MRC and Asthma UK Centre in Allergic Mechanisms of Asthma have discovered a key reason to why airways in the lungs of people with asthma change over time, a process called airway remodelling.

The small airways in the lungs of people with asthma tend to change as their lungs respond to the presence of particles such as dust, pollen and mould spores in the air they breathe. Airway remodelling can also be compounded by viruses and bacteria, or even by the body's response to strong emotions or changes in air temperature.

There is no proven way of reversing airway remodelling once it has occurred.

An important aspect of airway remodelling is changes to the muscle cells that line the airways. In people with asthma, these cells tend to multiply and become larger, increasing their ability to squeeze the airways and cause breathing difficulties. The muscle cells also become twitchy and likely to contract at the slightest provocation.

Professor Tak Lee and colleagues have focused their attention on the movement of calcium atoms in and out of muscle cells, and they believe that they have discovered a key reason why muscle cells in the lungs of people with asthma become twitchy and over-sensitive.

Calcium is the most plentiful mineral in the human body. It is essential for our bones and teeth, and its movement in and out of muscle cells causes them to contract or relax.

Professor Lee and his colleagues examined whether the defective movement of calcium might be responsible for the over-sensitivity and excessive contraction of muscle cells in asthma. The amount of free-floating calcium in muscle cells is controlled by a series of channels and pumps that either increase or decrease calcium levels. One of these pumps is called SERCA2. It causes muscle cells to relax by pumping calcium out of the main body of the cell.

The Asthma UK-supported scientists studied muscle cells from the airways of people with moderate asthma; they experience daily asthma symptoms and need both preventer and relieve inhalers to keep their symptoms under control.

The scientists compared these cells to those from people who either had mild asthma or didn't have asthma at all. They discovered that in people with moderate asthma SERCA2 levels were reduced, lowering the cells' capacity to remove calcium. They also found that if they removed SERCA2 from the cells of people who didn't have asthma, these cells started to behave more like asthma cells.

These discoveries suggest that a lack of SERCA2 in airway muscle cells might play an important role in causing asthma symptoms. Professor Lee suggests that replacing SERCA2 in these cells might be an effective way of creating new asthma treatments that reduce asthma symptoms and prevent the long-term lung changes that can make some people's asthma almost impossible to control.

Dr Elaine Vickers, Research Relations Manager at Asthma UK, said: ‘Professor Lee's detailed research into the causes of asthma symptoms provides us with vital clues as to how such symptoms could be stopped. ‘He has uncovered important information, which we hope will lead to the creation of effective new treatments for the millions of the people in the UK affected by asthma symptoms.'

This research was also supported by the Medical Research Council; the Dr Hadwen Trust for Humane Research; the Guy's and St Thomas' NHS Foundation Trust; and King's College London National Institute for Health Research Biomedical Research Centre. It was published in the scientific journal Proceedings of the National Academy of Sciences.