Abstract

Acute exacerbations are the major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Rhinovirus, which causes acute exacerbations may also accelerate progression of lung disease in these patients. Current therapies reduces the respiratory symptoms and does not treat the root cause of exacerbations effectively. We hypothesized that quercetin, a potent antioxidant and anti-inflammatory agent with antiviral properties may be useful in treating rhinovirus-induced changes in COPD. Mice with COPD phenotype maintained on control or quercetin diet and normal mice were infected with sham or rhinovirus, and after 14 days mice were examined for changes in lung mechanics and lung inflammation. Rhinovirus-infected normal mice showed no changes in lung mechanics or histology. In contrast, rhinovirus-infected mice with COPD phenotype showed reduction in elastic recoiling and increase in lung inflammation, goblet cell metaplasia, and airways cholinergic responsiveness compared to sham-infected mice. Interestingly, rhinovirus-infected mice with COPD phenotype also showed accumulation of neutrophils, CD11b+/CD11c+ macrophages and CD8+ T cells in the lungs. Quercetin supplementation attenuated rhinovirus-induced all the pathologic changes in mice with COPD phenotype. Together these results indicate that quercetin effectively mitigates rhinovirus-induced progression of lung disease in a mouse model of COPD. Therefore, quercetin may be beneficial in the treatment of rhinovirus-associated exacerbations and preventing progression of lung disease in COPD.

Highlights

  • Chronic obstructive pulmonary disease (COPD), a relatively prevalent lung disease is one of the leading causes of morbidity and mortality worldwide [1]

  • Better therapies with relatively no side effects are needed for treatment of COPD exacerbations associated with rhinovirus infections

  • To examine whether mice with COPD phenotype resolves lung inflammation induced by RV, we examined lung histology at 14 days post-RV infection

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Summary

Introduction

Chronic obstructive pulmonary disease (COPD), a relatively prevalent lung disease is one of the leading causes of morbidity and mortality worldwide [1]. Respiratory infections are responsible for 50 to 70% of COPD exacerbations and approximately 1/3rd to 1/2 of these were associated with virus infections with rhinovirus (RV) being the most commonly detected virus [5,6]. Accumulating clinical evidence indicate casual relationship between RV infection and worsening of both upper and lower respiratory symptoms, and development of secondary bacterial infections in COPD patients [5,7]. An elegant study involving experimental infection of COPD or normal subjects patients with RV provided direct evidence demonstrating that RV induces respiratory illness which is more severe and prolonged in COPD than in normal [8]. Better therapies with relatively no side effects are needed for treatment of COPD exacerbations associated with rhinovirus infections

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