Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma

Background: The nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations. Methods: We used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects. Results: Compared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68(+) macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45(+), CD68(+), and CD20(+) cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4(+) cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = 2 0.89, P = .029), the PC10 correlated inversely with CD4 1 (r = 2 0.67, P = .023) and CD8(+) cells (r = 2 0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20(+) cells (r = 2 0.65, P = .03), and higher epithelial CD8(+) cell counts were significantly associated with a greater maximum fall in FEV1 (r = 2 0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024). Conclusions: In subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/ macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during infection are related to virus load and physiologic and clinical severity, whereas mast cells are related to greater lung function.