Research reveals exactly how coughing is triggered by environmental irritants

Findings suggest new target for potential cough treatments - <em>News Release</em>

Imperial College London News Release

Under strict embargo until:
00.01 EST/05.01 GMT
Monday 23 November 2009

Scientists have revealed how environmental irritants such as air pollution and cigarette smoke cause people to cough, in research published today in the American Journal of Respiratory and Critical Care Medicine. The authors of the study, from Imperial College London and the University of Hull, have identified the reaction inside the lungs that can trigger coughing when a person is exposed to particular irritants in the air. They suggest that their findings may ultimately lead to the development of new treatments for chronic coughing.

Coughing is the most common reason for people visiting a family doctor. Treatment options are limited for people with chronic coughing; a recent study concluded that over-the-counter remedies are ineffective and there is increasing concern about the safety of these therapies in children.

Today's study indicates, for the first time, how coughing can be triggered when a person is exposed to certain irritants in the air. It shows that the irritants can switch on receptor proteins called TRPA1 on the surface of nerve endings in the lungs. This switches on sensory nerves, which then trigger a cough reflex. The researchers say coughing could potentially be treated by blocking TRPA1 receptors, to stop irritants in the air from setting off this chain reaction. They hope that this could ultimately help millions of people whose lives are affected by chronic coughing.

Professor Maria Belvisi, corresponding author of the study from the National Heart and Lung Institute at Imperial College London, said: "For some people, chronic coughing can be annoying and uncomfortable, but for others it can be distressing and can have a severe impact on their quality of life. Many people say that certain things in the air can make them cough and we are very excited that we have shown, for the first time, exactly what is probably happening inside the lungs. Now that we think we have cracked the mechanism, we can start investigating whether we can stop people from coughing excessively by blocking the receptor protein that triggers it."

To reach their conclusions, the researchers first looked at sensory nerves from mice, guinea pigs and humans, and showed that the receptors on the sensory nerves were activated by a number of irritants, including a key compound in cigarette smoke (acrolein) and a chemical called cinnamaldehyde. The researchers then blocked the receptors and showed that these substances no longer activated the nerves.

Over-the-counter cough treatments are often ineffective

To establish whether activating the receptor causes coughing, the researchers looked at the effect of acrolein on guinea pigs, as they have a coughing reflex. The researchers assessed the guinea pigs' coughing after inhaling acrolein. The compound caused coughing, and the higher the concentration, the more the guinea pigs coughed. The researchers then showed that blocking the receptor using a drug significantly reduced the guinea pigs' coughing response to the compound.

Finally, researchers led by Professor Alyn Morice at the University of Hull looked at the effect of inhaling the chemical cinnamaldehyde in humans. Ten healthy, non- smoking volunteers inhaled the chemical, as well as control substances. The researchers measured their cough response on five occasions, 2-3 days apart. All of the volunteers coughed after inhaling the compound.

This research was funded by the Medical Research Council.

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Imperial College London
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Notes to Editors:

1. "TRPA1 Agonists Evoke Coughing in Guinea-Pig and Human Volunteers" American Journal of Respiratory and Critical Care Medicine, Monday 23 November 2009.
Corresponding author: Professor Maria Belvisi, Imperial College London (For a full list of authors, please see paper)

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 13,000 students and 6,000 staff of the highest international quality.

Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy.

Website: www.imperial.ac.uk

3. About the University of Hull

The University of Hull is one of the world's top 500 universities and is well known for the discovery of liquid crystals, for which the Department of Chemistry received the Queen's Award for Technological Achievement. Philip Larkin, one of the greatest English poets of the twentieth century, was the University's librarian for 30 years and he wrote some of his most celebrated works at the University. Famous alumni include: Lord Dearing, Roger McGough CBE, John McCarthy and Anthony Minghella.

For more information visit: www.hull.ac.uk

4. The University of Hull is host to the largest specialist cough clinic in Europe

5. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing envi ronment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk