Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation.
BACKGROUND
Respiratory virus infections are associated with chronic obstructive pulmonary disease (COPD) exacerbations, but a causative relationship has not been proven. Studies of naturally occurring exacerbations are difficult and the mechanisms linking virus infection to exacerbations are poorly understood. We hypothesized that experimental rhinovirus infection in subjects with COPD would reproduce the features of naturally occurring COPD exacerbations and is a valid model of COPD exacerbations.


OBJECTIVE
To evaluate experimental rhinovirus infection as a model of COPD exacerbation and to investigate the mechanisms of virus-induced exacerbations.


METHODS
We used experimental rhinovirus infection in 13 subjects with COPD and 13 nonobstructed control subjects to investigate clinical, physiologic, pathologic, and antiviral responses and relationships between virus load and these outcomes.


RESULTS
Clinical data; inflammatory mediators in blood, sputum, and bronchoalveolar lavage; and viral load in nasal lavage, sputum, and bronchoalveolar lavage were measured at baseline and after infection with rhinovirus 16. After rhinovirus infection subjects with COPD developed lower respiratory symptoms, airflow obstruction, and systemic and airway inflammation that were greater and more prolonged compared with the control group. Neutrophil markers in sputum related to clinical outcomes and virus load correlated with inflammatory markers. Virus load was higher and IFN production by bronchoalveolar lavage cells was impaired in the subjects with COPD.


CONCLUSIONS
We have developed a new model of COPD exacerbation that strongly supports a causal relationship between rhinovirus infection and COPD exacerbations. Impaired IFN production and neutrophilic inflammation may be important mechanisms in virus-induced COPD exacerbations.
Mallia
Patrick
P
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
Message
Simon D
SD
Gielen
Vera
V
Contoli
Marco
M
Gray
Katrina
K
Kebadze
Tatiana
T
Aniscenko
Julia
J
Laza-Stanca
Vasile
V
Edwards
Michael R
MR
Slater
Louise
L
Papi
Alberto
A
Stanciu
Luminita A
LA
Kon
Onn M
OM
Johnson
Malcolm
M
Johnston
Sebastian L
SL
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010850:Picornaviridae Infections; D029424:Pulmonary Disease, Chronic Obstructive / Q000821:virology*; D012229:Rhinovirus; D019562:Viral Load
D018836:Inflammation Mediators