Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma.
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.
Department of Respiratory Medicine; National Heart and Lung Institute, Imperial College London, London, England.
Jie
J
Zhu
Department of Respiratory Medicine; Imperial College Healthcare NHS Trust, London, England.
Simon D
SD
Message
National Heart and Lung Institute, Imperial College London, London, England.
Yusheng
Y
Qiu
Department of Respiratory Medicine; Imperial College Healthcare NHS Trust, London, England.
Patrick
P
Mallia
Department of Respiratory Medicine.
Tatiana
T
Kebadze
Department of Respiratory Medicine; Imperial College Healthcare NHS Trust, London, England; Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy.
Marco
M
Contoli
Centocor Inc, Malvern, PA.
Christine K
CK
Ward
Centocor Inc, Malvern, PA.
Elliot S
ES
Barnathan
Centocor Inc, Malvern, PA.
Mary Ann
MA
Mascelli
Imperial College Healthcare NHS Trust, London, England.
Onn M
OM
Kon
Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy.
Alberto
A
Papi
Department of Respiratory Medicine.
Luminita A
LA
Stanciu
National Heart and Lung Institute, Imperial College London, London, England.
Peter K
PK
Jeffery
Department of Respiratory Medicine; Imperial College Healthcare NHS Trust, London, England. Electronic address: s.johnston@imperial.ac.uk.
Sebastian L
SL
Johnston
D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000821:virology; D003139:Common Cold / Q000150:complications / Q000276:immunology*; D015897:Comorbidity; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology / Q000821:virology; D008214:Lymphocytes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D011014:Pneumonia / Q000276:immunology* / Q000821:virology*; D012229:Rhinovirus / Q000302:isolation & purification; D012720:Severity of Illness Index; D019562:Viral Load