CT Scans Indentify Smokers At Risk Of Emphysema

Using CT scans to measure blood flow in the lungs of people who smoke may offer a way to identify which smokers are most at risk of emphysema before the disease damages and eventually destroys areas of the lungs, according to a new study published in PNAS

The study found that smokers who have very subtle signs of emphysema, but still have normal lung function, have very different blood flow patterns in their lungs compared to non-smokers and smokers without signs of emphysema.This difference could be used to identify smokers at increased risk of emphysema and allow for early intervention.

As many as 24 million Americans have chronic obstructive pulmonary disease (COPD) -- a group of serious lung diseases that includes emphysema -- and COPD is the fourth leading cause of death nationwide. Because COPD is a group of different diseases, identifying more effective treatments may hinge on distinguishing between these diseases and targeting them separately.

The team used multi-detector row CT imaging to measure blood flow patterns in the lungs of 41 study participants -- 17 non-smokers and 24 smokers. All the participants had normal lung function, but 12 of the smokers had very subtle signs of emphysema. The CT scans showed that these 12 individuals had the most disrupted patterns of blood flow compared to the other participants.

The findings also support the idea that abnormal blood flow occurs before emphysema develops.

"Although the underlying causes of emphysema are not well understood, smoking increases the risk of developing the disease," said lead study author Eric Hoffman, Ph.D., UI professor of radiology, internal medicine and biomedical engineering.

"Our study suggests that some smokers have an abnormal response to inflammation in their lungs; instead of sending more blood to the inflamed areas to help repair the damage, blood flow is turned off and the inflamed areas deteriorate."

The cellular pathway that turns off blood flow is helpful when an area of the lung has become permanently blocked and cannot be rescued. In that case, the lung "optimizes gas exchange" and stops supplying the area with blood. However, lung inflammation caused by smoking can be resolved and resultant damage repaired by increased blood flow, which brings oxygen and helpful cellular components to the site of injury.

This study suggests that the ability to distinguish when to turn off or when to ramp up blood flow is defective in some people -- probably due to genetic differences. If this genetic difference is coupled with smoking, which increases lung inflammation, that could increase the risk of developing emphysema.



CT Scans Indentify Smokers At Risk For Emphysema

Be cool without dying: New technique reduces tobacco smoke damage to lungs

Researchers in Australia have demonstrated that blocking a certain protein can reduce or prevent cigarette smoke-induced lung inflammation in mice. Inflammation underlies the disease process of chronic obstructive pulmonary disease (COPD) and many other smoking-related ailments.

The findings have been published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Cigarette smoking causes lung inflammation, which can lead to oxidative stress, emphysema, small airway fibrosis, mucus hypersecretion and progressive airflow limitation. Since the inflammatory reaction to cigarette smoke responds poorly to current anti-inflammatory treatments, there is intense research to identify more effective therapies for cigarette smoke-induce lung damage.

Granulocyte macrophage-colony stimulating factor (GM-CSF) is of special interest because it governs the growth, activation and survival of leukocytes directly implicated in the pathogenesis of COPD.

Cigarette smoke triggers the release of GM-CSF and other cytokines and chemokines which cause activation and recruitment of more inflammatory cells into the lung,thereby perpetuating the inflammatory response and exacerbating ongoing inflammation. These activated and recruited inflammatory cells also release proteases such as matrix metalloproteinase (MMP)-12, which destroy the lung tissue, resulting in emphysema.

The research team from the University of Melbourne set out to determine whether blocking GM-CSF could reduce the inflammation and other deleterious effects of cigarette smoke exposure in mice.

To do so, they exposed a group of mice, half of which had been treated with a GM-CSF blocking agent, anti-GM-CSF, and half of which were controls, to the equivalent of nine cigarettes of smoke each day for four days. At the end of four days, the mice were killed and their lung tissue was examined for the presence of inflammatory cells.

"We found that anti-GM-CSF strongly reduced the number of potentially harmful white blood cells that infiltrate the lung after smoke exposure, as well as inhibiting the pro-inflammatory cytokine tumor necrosis factor (TNF)-, the chemokine macrophage inflammatory protein-2 (MIP-2), which coordinates the movement of white blood cells into the lung. It also inhibited the protease MMP-12, which is known as one of the main enzymes able to destroy lung tissue," said lead researcher on the study, Ross Vlahos, Ph.D., a senior research fellow with the lung disease research group at the University of Melbourne. "Cigarette smoke-exposed mice that were treated with an anti-GM-CSF had significantly less lung inflammation in comparison to untreated mice. This indicates that GM-CSF is a key mediator in smoke-induced lung inflammation and its neutralization may have therapeutic implications in diseases such as COPD."

These results, though preliminary, may illuminate a new pathway toward fighting smoke-related disease, specifically COPD. "Short-term models often translate into benefits in longer-term models. We still need to develop new methods and agents to test this idea long term and we also need to learn if it is effective in reversing longstanding disease," explained Dr. Vlahos.

In future research, Dr. Vlahos hopes to test whether GM-CSF could be a key target in other disease processes. "We want to understand exactly how blocking GM-CSF alters disease processes at the cellular and molecular levels so we can use this fine detail to make other treatments."

But this research is no free pass for patients to continue smoking, he warned: "Our treatment deals with cigarette smoke-induced lung inflammation involved in COPD, not cancer and other smoking-related ailments. Quitting remains the best and only cure for smoking-related lung disease."

Be cool without dying: New technique reduces tobacco smoke damage to lungs in mice