Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice.
BACKGROUND
Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD.


METHODS
C57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV).


RESULTS
Unlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.


CONCLUSIONS
These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.
Shyamala
S
Ganesan
Adam T
AT
Comstock
Brenton
B
Kinker
Peter
P
Mancuso
James M
JM
Beck
Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W, Medical Center Dr,, Ann Arbor, MI 48109-5688, USA. usajjan@umich.edu.
Uma S
US
Sajjan
D000818:Animals; D006192:Haemophilus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006193:Haemophilus influenzae; D006367:HeLa Cells; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects*