Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD

Abstract

Background: Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.

Objectives: We sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16-induced COPD exacerbations and its relationship to disease severity.

Methods: Bronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests.

Results: RV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8⁺ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4⁺ T lymphocytes, and CD20⁺ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8⁺ T lymphocytes but fewer numbers of CD4⁺ T lymphocytes and CD20⁺ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function.

Conclusions: Experimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations.

Keywords: Rhinovirus infection; chronic obstructive pulmonary disease exacerbation; eosinophils; inflammation.