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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 and B, Changes in counts of epithelial (A) and subepithelial (B) neutrophils and CD68+ cells from baseline to d 4 postinfection in bronchial biopsy specimens from subjects with and without asthma. Data are presented as change in the number of positive cells per 0.1 mm2 of epithelium or per square millimeter of subepithelium. ○ and ● show individual changes in counts, and horizontal bars show median values (Mann-Whitney U test).
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fig03: A and B, Changes in counts of epithelial (A) and subepithelial (B) neutrophils and CD68+ cells from baseline to d 4 postinfection in bronchial biopsy specimens from subjects with and without asthma. Data are presented as change in the number of positive cells per 0.1 mm2 of epithelium or per square millimeter of subepithelium. ○ and ● show individual changes in counts, and horizontal bars show median values (Mann-Whitney U test).

Mentions: To investigate differences in inflammatory responses of subjects with and without asthma to RV infection, the magnitude of the changes of inflammatory cell counts from baseline to infection was compared. The changes in numbers of both epithelial (P = .0036) and subepithelial (P = .018) neutrophils from baseline to day 4 infection in subjects with asthma were significantly greater than those in normal subjects (Figs 3A, 3B). The changes in subepithelial CD68+ cell counts from baseline to day 4 infection in subjects with asthma were also significantly greater than those in normal subjects (P = .025) (Fig 3B). No significant differences with respect to changes in numbers of other inflammatory cell phenotypes were seen between groups from baseline to day 4 or week 6.


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 and B, Changes in counts of epithelial (A) and subepithelial (B) neutrophils and CD68+ cells from baseline to d 4 postinfection in bronchial biopsy specimens from subjects with and without asthma. Data are presented as change in the number of positive cells per 0.1 mm2 of epithelium or per square millimeter of subepithelium. ○ and ● show individual changes in counts, and horizontal bars show median values (Mann-Whitney U test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: A and B, Changes in counts of epithelial (A) and subepithelial (B) neutrophils and CD68+ cells from baseline to d 4 postinfection in bronchial biopsy specimens from subjects with and without asthma. Data are presented as change in the number of positive cells per 0.1 mm2 of epithelium or per square millimeter of subepithelium. ○ and ● show individual changes in counts, and horizontal bars show median values (Mann-Whitney U test).
Mentions: To investigate differences in inflammatory responses of subjects with and without asthma to RV infection, the magnitude of the changes of inflammatory cell counts from baseline to infection was compared. The changes in numbers of both epithelial (P = .0036) and subepithelial (P = .018) neutrophils from baseline to day 4 infection in subjects with asthma were significantly greater than those in normal subjects (Figs 3A, 3B). The changes in subepithelial CD68+ cell counts from baseline to day 4 infection in subjects with asthma were also significantly greater than those in normal subjects (P = .025) (Fig 3B). No significant differences with respect to changes in numbers of other inflammatory cell phenotypes were seen between groups from baseline to day 4 or week 6.

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