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Smoking May Alter Immune Response In COPD Exacerbations

by VR Sreeraman on Apr 8 2009 3:20 PM

Smoking cigarettes is not the only risk factor for chronic obstructive pulmonary disease (COPD), it may also change the body’s immune responses to bacteria that commonly cause exacerbations of the disease, according to a study in mice.

"It is well established that smoking is the main risk factor for COPD. But our research also suggests that cigarette smoke substantially changes the immune response to bacteria, which means that patients with COPD who smoke are weakening their body’s ability to deal effectively with bacterial invaders. This may cause even further progression of the disease," said Martin Stampfli, Ph.D., an associate professor at McMaster University, the principle investigator of the study.

"We wanted to see whether and how cigarette smoke would change the inflammatory response to the bacteria that is the culprit behind many COPD exacerbations, nontypeable Haemophilus influenzae or NTHI," Stampfli added.

Researchers tested the effects of cigarette smoke exposure on inflammation and immune response in mice that were exposed to cigarette smoke twice daily five days a week for either eight weeks or four days then challenged with an intranasal inoculation of NTHI.

The cigarette smoke exposure roughly approximated that of an "average" human smoker (within the limitations of a model with differing metabolic processes.) Control mice were not exposed to cigarette smoke, but were inoculated with NTHI as were the cigarette smoke-exposed mice.

The researchers found that mice that were exposed to cigarette smoke, whether for four days or for eight weeks, showed distinct shifts in their immune-response profile, namely an increase in inflammation of the lungs after the NTHI challenge, increased weight-loss in response to the bacterial infection and, notably, a shift in the expression of inflammatory markers.

"Many interventions are developed with a homeostatic model in mind. 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," said Stampfli.

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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.

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.

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"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," Stampfli said.

"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," Stampfli added.

The results were published in the second issue of April of the American Journal of Respiratory and Critical Care Medicine.

Source-ANI
SRM


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