Chest
Volume 145, Issue 6, June 2014, Pages 1219-1229
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Original Research
Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma

https://doi.org/10.1378/chest.13-1567Get rights and content
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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.

Abbreviations

PC10
10% fall in FEV1
PEF
peak expiratory flow
RV
rhinovirus

Cited by (0)

Drs Zhu and Message contributed equally to this work.

Funding/Support: This work was supported by a Medical Research Council Clinical Research Fellowship and a British Medical Association HC Roscoe Fellowship (to Dr Message), British Lung Foundation/Severin Wunderman Family Foundation Lung Research Programme [Grant P00/2], Asthma UK [Grants 02/027 and 05/067], Wellcome Trust [Grants 063717 and 083567/Z/07/Z], the National Institute for Health Research Biomedical Research Centre and Clinical Lecturer funding schemes, Centocor Inc, Medical Research Council Centre [Grant G1000758], and European Research Council FP7 Advanced [Grant 233015] (to Prof Johnston).

This is a Wellcome-Trust-compliant open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/).