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Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma.

Zhu J, Message SD, Qiu Y, Mallia P, Kebadze T, Contoli M, Ward CK, Barnathan ES, Mascelli MA, Kon OM, Papi A, Stanciu LA, Jeffery PK, Johnston SL - Chest (2014)

Bottom Line: 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 = -0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023) and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = -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).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.

View Article: PubMed Central - PubMed

ABSTRACT

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 = -0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023) and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = -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.

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Cell counts in bronchial biopsy specimens of subjects with and without asthma at baseline and days 4 and 6 of rhinovirus 16 infection. A, CD45+ cells. B, Epithelial neutrophils. C, Subepithelial neutrophils. D, CD68+ cells. E, CD4+ cells. Data are presented as the number of positive cells per square millimeter of subepithelium or per 0.1 mm2 of epithelium. △ and ▲ show individual counts, and horizontal bars show median values (Wilcoxon matched pairs and Mann-Whitney U tests).
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fig02: Cell counts in bronchial biopsy specimens of subjects with and without asthma at baseline and days 4 and 6 of rhinovirus 16 infection. A, CD45+ cells. B, Epithelial neutrophils. C, Subepithelial neutrophils. D, CD68+ cells. E, CD4+ cells. Data are presented as the number of positive cells per square millimeter of subepithelium or per 0.1 mm2 of epithelium. △ and ▲ show individual counts, and horizontal bars show median values (Wilcoxon matched pairs and Mann-Whitney U tests).

Mentions: The number of subepithelial CD45+ cells in subjects with asthma was significantly greater at both baseline (P = .014) and day 4 infection (P = .025) (Fig 2A) than in normal subjects at the same time points. Compared with their respective baseline and day 4 values, the number of subepithelial CD45+ cells was significantly less at week 6 postinfection in both normal subjects (P = .038 and P = .006) and subjects with asthma (P = .003 and P = .0006) (Fig 2A). There were no significant differences in counts of epithelial CD45+ cells within and between groups.


Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma.

Zhu J, Message SD, Qiu Y, Mallia P, Kebadze T, Contoli M, Ward CK, Barnathan ES, Mascelli MA, Kon OM, Papi A, Stanciu LA, Jeffery PK, Johnston SL - Chest (2014)

Cell counts in bronchial biopsy specimens of subjects with and without asthma at baseline and days 4 and 6 of rhinovirus 16 infection. A, CD45+ cells. B, Epithelial neutrophils. C, Subepithelial neutrophils. D, CD68+ cells. E, CD4+ cells. Data are presented as the number of positive cells per square millimeter of subepithelium or per 0.1 mm2 of epithelium. △ and ▲ show individual counts, and horizontal bars show median values (Wilcoxon matched pairs and Mann-Whitney U tests).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042510&req=5

fig02: Cell counts in bronchial biopsy specimens of subjects with and without asthma at baseline and days 4 and 6 of rhinovirus 16 infection. A, CD45+ cells. B, Epithelial neutrophils. C, Subepithelial neutrophils. D, CD68+ cells. E, CD4+ cells. Data are presented as the number of positive cells per square millimeter of subepithelium or per 0.1 mm2 of epithelium. △ and ▲ show individual counts, and horizontal bars show median values (Wilcoxon matched pairs and Mann-Whitney U tests).
Mentions: The number of subepithelial CD45+ cells in subjects with asthma was significantly greater at both baseline (P = .014) and day 4 infection (P = .025) (Fig 2A) than in normal subjects at the same time points. Compared with their respective baseline and day 4 values, the number of subepithelial CD45+ cells was significantly less at week 6 postinfection in both normal subjects (P = .038 and P = .006) and subjects with asthma (P = .003 and P = .0006) (Fig 2A). There were no significant differences in counts of epithelial CD45+ cells within and between groups.

Bottom Line: 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 = -0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023) and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = -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).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.

View Article: PubMed Central - PubMed

ABSTRACT

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 = -0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023) and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = -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.

Show MeSH
Related in: MedlinePlus