Research Profile – Risky Breathing

Vancouver researchers are studying why women have a higher risk than men for chronic obstructive lung disease and lung cancer.

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There is something about women's lungs that increases their risk of chronic obstructive pulmonary disease (COPD) and lung cancer. Researchers in Vancouver are making progress in the effort to identify this mystery risk factor.

COPD is the third leading killer of women in Canada, following heart disease and cancer. A woman's risk of developing COPD is 30% higher than a man's, even if they have identical risk factors, according to Dr. Donald Sin, chief of respiratory medicine at St. Paul's Hospital. He is also Canadian Research Chair in Chronic Obstructive Lung Disease and a professor of medicine at the University of British Columbia.

It's anticipated that within 30 years the number of women with COPD will far outstrip that in men, in part to due greater numbers of female smokers. But even if identical numbers of men and women smoked, a larger percentage of women would develop COPD and lung cancer.

"We think that women, compared to men, have increased airway and systemic inflammation in response to tobacco smoke exposure," he says. Indeed, research in his laboratory provides compelling evidence.

When people smoke, or are exposed to air pollution, specialized immune cells in the lungs cause inflammation to try to control or clear out the irritants. Coughing and extra phlegm are both signs of these inflammatory cells in action. With constant or frequent exposure, these inflammatory cells end up causing damage to the lung tissue.

"The airways become what we call 'remodelled' – they become progressively narrow – due to this collateral damage," says Dr. Sin.

The narrowing has several possible causes. For one, the tissue lining the airways becomes chronically inflamed or swollen, causing blockages and reducing airflow. Progressive scarring in the airways can happen, creating layers of scar tissue. This makes lung tissue stiff and less elastic when breathing. There can also be a chronic build-up of thick 'tenacious' mucous inside the airways.

The presence of female sex hormones such as progesterone in the lungs may be one of the factors that increases women's risk of COPD and lung cancer.

"In our work, we found out that when lung cells are exposed to progesterone, they go kind of wild and produce very thick tenacious mucous," Dr. Sin says. Under normal circumstances, this thick mucus helps trap irritants that can be eventually coughed up. But, with constant exposure to irritants (such as with habitual smoking) this thick mucus stays put, trapping viruses and bacteria that are not cleared properly.

"The bacteria can sit there and multiply and cause all sorts of damage," he said. One of the normal roles of progesterone is to protect cells from dying, which is normally a good thing. "But if you smoke and progesterone causes damaged cells to live longer than they should – those cells can develop mutations and may become cancerous," he said.

In women, this is especially problematic. It is suspected that because some cancer tumours actually have estrogen receptors, they may be able to "use female sex hormones to proliferate and prevent them from being destroyed by the host's immune cells," says Dr. Sin. This is what the researchers are investigating right now, with the support of the Canadian Institutes of Health Research.

The eventual goal is to find treatments for patients with these diseases. "We think that by trying to understand the mechanistic process linking women – and particularly female smoking – with COPD and lung cancer that we can come up with novel targets for therapy," says Dr. Sin.

"Once you turn on the bad gene for COPD with cigarette smoking, it's very hard to put the genie back in the bottle."
– Dr. Donald Sin, University of British Columbia