A pill that could mitigate some of the negative health effects of smoking is a step closer to reality.

Researchers have identified 28 molecules that are produced in abnormal amounts in cells lining the airways of smokers. If the levels of these molecules could be restored to that of non-smokers it might allow chronic smokers who have been unable to quit to improve their health prospects. It might also enable people to smoke without significant damage to their health.

Avrum Spira at Boston University School of Medicine and his colleagues took samples of cells from the airways of 10 smokers and 10 non-smokers and identified 28 microRNAs - molecules that control the expression of whole networks of related genes - that were perturbed in the smokers.

"These microRNAs serve to regulate the gene expression changes occurring in people who smoke and who get smoking related diseases, including cancer," says Spira.

One of these microRNAs, called mir-218, appears to control a group of genes that usually protect lung and airway cells from the oxidative damage caused by smoke. "We think the level of activity [of mir-218] is crucial in how a smoker defends his or herself against injury and potential development of lung disease."

Other microRNAs identified help to regulate the proliferation and growth of airway cells.

Damage test

Giving supplements of mir-218 to smokers, or developing a drug that restores levels of disrupted microRNAs to normal could mitigate some of the damaging effects of smoke. "We might be able to alter the host's response to tobacco smoke so that it is a protective one," says Spira.

A test could also be developed that tells smokers how much damage they are doing to their lungs. In the current study, cells were taken from volunteers airways using a small brush attached to a flexible plastic tube - although Spira says that cells lining the mouth and nose may display similar changes in response to smoke.

"We could use these epithelial cells as a kind of canary in the goldmine to tell us what is going on deeper in the lungs," he says. "Based on the activity of these microRNAs, we could potentially decide whether someone is responding appropriately or not to the toxin, and is therefore at higher risk of developing disease further down the road."

Journal reference: Proceedings of the National Academy of Science (DOI: 10.1073/pnas.0806383106)