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Cigarette smoke may alter immune response in COPD exacerbations
Date:4/6/2009

e expression of inflammatory markers.

"Many interventions are developed with a homeostatic model in mind," said Dr. Stmpfli. "However, if our findings are borne out in clinical research, they would indicate that treatment targets for smokers with COPD may be markedly different than in non-smokers. Smoking may change the underlying inflammatory pathways elicited after bacterial infection."

Because of the shift in the inflammatory profile, the researchers wondered if it would have an effect on the efficacy of treatment with the usual corticosteroids.

Interestingly, they found that while the corticosteroid dexamethasone was effective in controlling the inflammation following bacterial challenge in both control and cigarette smoke-exposed mice, but it appeared to compromise the body's ability to clear the bacteria from the lungs.

"This was true for both control- and cigarette smoke-exposed mice and raises questions about the long-term use of corticosteroids in COPD. Certainly, there is evidence that corticosteroid treatment reduces the number of exacerbations in patients with COPD. This, however, is associated with occurrence of pneumonia, which is mirrored by our results. Therefore, inflammation is not altogether bad in the context of a bacterial infection, as it is required to clear the bacteria. It is the excessive inflammation observed in smokers that is of concern, as it may lead to lung damage."

The researchers note that the NTHI bacterium is an obligate human pathogen, and therefore an imperfect fit for a mouse model of COPD. "In the context of this present study, NTHI challenge was used as a tool to address the hypothesis of cigarette smoke exposure on the ensuing inflammatory response, and may not be perfectly suited to address pulmonary clearance, as a mouse-adapted pathogen may demonstrate different kinetics of clearance," Dr. Stmpfli noted.

Dr. Stmpfli intends to focus future research on detailing the pr
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Contact: Keely Savoie
ksavoie@thoracic.org
212-315-8620
American Thoracic Society
Source:Eurekalert

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