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Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice.

Ganesan S, Comstock AT, Kinker B, Mancuso P, Beck JM, Sajjan US - Respir. Res. (2014)

Bottom Line: 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.These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W, Medical Center Dr,, Ann Arbor, MI 48109-5688, USA. usajjan@umich.edu.

ABSTRACT

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.

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Related in: MedlinePlus

Airways responsiveness to methacholine challenge following RV infection. RA, CS, HK-NTHi or CS/HK-NTHi-exposed mice were either infected with RV or equal volume of sham. Four days later, total respiratory system resistance was measured by plethysmography. Data represent mean ± SEM from 3 mice per group (* different from respective sham-infected animals, p ≤ 0.05, two-way ANOVA).
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Figure 8: Airways responsiveness to methacholine challenge following RV infection. RA, CS, HK-NTHi or CS/HK-NTHi-exposed mice were either infected with RV or equal volume of sham. Four days later, total respiratory system resistance was measured by plethysmography. Data represent mean ± SEM from 3 mice per group (* different from respective sham-infected animals, p ≤ 0.05, two-way ANOVA).

Mentions: RV-infected mice, irrespective of prior exposure to CS. NTHi, or combination of CS/NTHi, showed an increase in airways resistance in response to methacholine challenge over respective sham-infected mice (Figure 8A to8D). However, CS/HK-NTHi-exposed mice infected with RV showed a much higher increase in airways resistance to methacholine challenge than similarly infected mice in other groups.


Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice.

Ganesan S, Comstock AT, Kinker B, Mancuso P, Beck JM, Sajjan US - Respir. Res. (2014)

Airways responsiveness to methacholine challenge following RV infection. RA, CS, HK-NTHi or CS/HK-NTHi-exposed mice were either infected with RV or equal volume of sham. Four days later, total respiratory system resistance was measured by plethysmography. Data represent mean ± SEM from 3 mice per group (* different from respective sham-infected animals, p ≤ 0.05, two-way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3926338&req=5

Figure 8: Airways responsiveness to methacholine challenge following RV infection. RA, CS, HK-NTHi or CS/HK-NTHi-exposed mice were either infected with RV or equal volume of sham. Four days later, total respiratory system resistance was measured by plethysmography. Data represent mean ± SEM from 3 mice per group (* different from respective sham-infected animals, p ≤ 0.05, two-way ANOVA).
Mentions: RV-infected mice, irrespective of prior exposure to CS. NTHi, or combination of CS/NTHi, showed an increase in airways resistance in response to methacholine challenge over respective sham-infected mice (Figure 8A to8D). However, CS/HK-NTHi-exposed mice infected with RV showed a much higher increase in airways resistance to methacholine challenge than similarly infected mice in other groups.

Bottom Line: 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.These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W, Medical Center Dr,, Ann Arbor, MI 48109-5688, USA. usajjan@umich.edu.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus