According to Australian researchers, cigarette smoke exposure permanently alters the cellular structure of the tissues in the airway from people with Chronic Obstructive Pulmonary Disease (COPD).  Causing airway thickening and even causing precancerous cells to increase long after cigarette smoke exposures has ended.

"We have demonstrated for the first time that the extracellular matrix (ECM) produced by fibroblasts following stimulation with cigarette smoke extract is functionally different than non-exposed ECM, and that the cigarette smoke itself may prime the airways in such a way to create an environment whereby airway remodeling is encouraged," wrote lead researcher David Krimmer, a PhD student who is working with senior investigator Dr. Brian Oliver at the Woolcock Institute of Medical Research, from the University of Sydney in Australia.

COPD, also known as emphysema and chronic bronchitis, is a very serious disease, and the third leading cause of death in the United States.

The primary cause is chronic exposure to particulate matter, most often cigarette smoke. While the cause of emphysematous destruction of the alveoli is likely due to the combination of they cytotoxic and pro-inflammatory activity of cigarette smoke, it is unknown whether cigarette smoke itself can cause thickening of the airway walls.

"We aimed to examine whether cigarette smoke extract alters the ECM deposited by primary human lung fibroblasts, and if smoke-induced ECM can alter proliferation and cytokine release," wrote Mr. Krimmer. "We also investigated whether the release of pro-fibrotic cytokines from fibroblasts were increased by cigarette smoke exposure."

Researchers examined the response of human lung tissue from donors with and without COPD to cigarette smoke extract (CSE). They found that CSE exposure induced a significant increase in fibronectin, a general cell adhesion molecule, deposition from the tissue of donors with COPD compared to donors without COPD.  

Similarly, they found that CSE up regulated the expression of perlecan, an ECM protein that is associated with tumor growth and angiogensis in COPD Lung Tissue. 

These findings demonstrate that cigarette smoke has the capacity to directly induce fibrotic changes. "as such, this will change the way researchers think about the etiology of fibrosis in COPD, " said Mr. Krimmer.

The researchers also found that CSE exposure caused the COPD tissue to express a significantly greater amount of IL-8, a marker of inflammation, than non-COPD tissue.

CSE-induced ECM caused fibroblasts to proliferate. "We've known for a long time that development of fibrosis is irreversible in people with COPD. Our findings suggest that cigarette smoking alters the composition of the lung in such a way that fibrosis become self-perpetuating," explained Mr. Krimmer. "Cigarette smoking is obviously bad for everyone; however, in light of our findings, cigarette smoking is likely to be especially dangerous in people with pre-existing COPD."

"It is our hope that further research on how and why this occurs will result in viable therapeutic targets for reducing the detrimental airway changes underlying COPD."

Published online in the American Thoracic Society's American Journal of Respiratory Cell and Molecular Biology.