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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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A-F, In subjects with asthma alone, correlations between total chest symptom score d 0 to 14 after the rhinovirus 16 infection period and counts of epithelial CD4+ cells (A), between fall in PC10 (log2) and counts of subepithelial neutrophils at d 4 (B), between PC10 at d 6 and counts of subepithelial CD3+ (C), CD4+ (D), and CD8+ (E) cells at d 4; and between PC20 at d 6 and counts of subepithelial CD20+ cells at d 4 (F) (Spearman rank correlation, n = 10 for all). PC10 = 10% fall in FEV1; PC20 = 20% fall in FEV1.
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fig05: A-F, In subjects with asthma alone, correlations between total chest symptom score d 0 to 14 after the rhinovirus 16 infection period and counts of epithelial CD4+ cells (A), between fall in PC10 (log2) and counts of subepithelial neutrophils at d 4 (B), between PC10 at d 6 and counts of subepithelial CD3+ (C), CD4+ (D), and CD8+ (E) cells at d 4; and between PC20 at d 6 and counts of subepithelial CD20+ cells at d 4 (F) (Spearman rank correlation, n = 10 for all). PC10 = 10% fall in FEV1; PC20 = 20% fall in FEV1.

Mentions: At day 4, epithelial CD4+ counts in subjects with asthma correlated with total chest symptom scores recorded during the 2-week postinfection period (r = 0.69, P = .029) (Fig 5A). Those with high subepithelial neutrophil counts had a significantly larger fall in the 10% fall in FEV1 (PC10) from baseline to day 6 postinfection (r = 0.89, P = .029) (Fig 5B). The PC10 at day 6 correlated inversely with subepithelial CD3+ (r = −0.81, P = .016) (Fig 5C), CD4+ (r = −0.67, P = .023) (Fig 5D), and CD8+ (r = −0.65, P = .03) (Fig 5E) cells, and the 20% fall in FEV1 at day 6 was inversely associated with subepithelial CD20+ cells (r = −0.65, P = .03) (Fig 5F).


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)

A-F, In subjects with asthma alone, correlations between total chest symptom score d 0 to 14 after the rhinovirus 16 infection period and counts of epithelial CD4+ cells (A), between fall in PC10 (log2) and counts of subepithelial neutrophils at d 4 (B), between PC10 at d 6 and counts of subepithelial CD3+ (C), CD4+ (D), and CD8+ (E) cells at d 4; and between PC20 at d 6 and counts of subepithelial CD20+ cells at d 4 (F) (Spearman rank correlation, n = 10 for all). PC10 = 10% fall in FEV1; PC20 = 20% fall in FEV1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: A-F, In subjects with asthma alone, correlations between total chest symptom score d 0 to 14 after the rhinovirus 16 infection period and counts of epithelial CD4+ cells (A), between fall in PC10 (log2) and counts of subepithelial neutrophils at d 4 (B), between PC10 at d 6 and counts of subepithelial CD3+ (C), CD4+ (D), and CD8+ (E) cells at d 4; and between PC20 at d 6 and counts of subepithelial CD20+ cells at d 4 (F) (Spearman rank correlation, n = 10 for all). PC10 = 10% fall in FEV1; PC20 = 20% fall in FEV1.
Mentions: At day 4, epithelial CD4+ counts in subjects with asthma correlated with total chest symptom scores recorded during the 2-week postinfection period (r = 0.69, P = .029) (Fig 5A). Those with high subepithelial neutrophil counts had a significantly larger fall in the 10% fall in FEV1 (PC10) from baseline to day 6 postinfection (r = 0.89, P = .029) (Fig 5B). The PC10 at day 6 correlated inversely with subepithelial CD3+ (r = −0.81, P = .016) (Fig 5C), CD4+ (r = −0.67, P = .023) (Fig 5D), and CD8+ (r = −0.65, P = .03) (Fig 5E) cells, and the 20% fall in FEV1 at day 6 was inversely associated with subepithelial CD20+ cells (r = −0.65, P = .03) (Fig 5F).

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