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

Title: Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma
Authors: 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
Item Type: Journal Article
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.
Issue Date: 1-Jun-2014
Date of Acceptance: 5-Dec-2013
URI: http://hdl.handle.net/10044/1/56595
DOI: https://dx.doi.org/10.1378/chest.13-1567
ISSN: 0012-3692
Publisher: Elsevier
Start Page: 1219
End Page: 1229
Journal / Book Title: Chest
Volume: 145
Issue: 6
Copyright Statement: Creative Commons Attribution 3.0 Unported (CC BY 3.0)
Sponsor/Funder: Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: 233015
G1000758
G1000758
Keywords: Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
BRONCHIAL BIOPSY SPECIMENS
MAST-CELLS
T-LYMPHOCYTES
COMMON COLD
MILD ASTHMA
ANTI-IGE
EXACERBATIONS
NEUTROPHILS
VIRUS
EOSINOPHILS
Adult
Asthma
Common Cold
Comorbidity
Eosinophils
Female
Humans
Lung
Lymphocytes
Macrophages, Alveolar
Male
Mast Cells
Neutrophils
Pneumonia
Rhinovirus
Severity of Illness Index
Viral Load
1103 Clinical Sciences
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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