Experimental Rhinovirus Infection as a Human Model of Chronic Obstructive Pulmonary Disease Exacerbation
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....
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| Published in | American journal of respiratory and critical care medicine Vol. 183; no. 6; pp. 734 - 742 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York, NY
American Thoracic Society
15.03.2011
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| Subjects | |
| Online Access | Get full text |
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| Summary: | 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.
To evaluate experimental rhinovirus infection as a model of COPD exacerbation and to investigate the mechanisms of virus-induced exacerbations.
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.
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.
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. |
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| Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-General Information-1 content type line 14 ObjectType-Feature-3 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 Supported by an unrestricted grant from GlaxoSmithKline, a Medical Research Council Clinical Research Fellowship (to S.D.M.), British Medical Association H.C. Roscoe Fellowships (to S.D.M. and P.M.), British Lung Foundation/Severin Wunderman Family Foundation Lung Research Program grant P00/2, Wellcome Trust grant 083567/Z/07/Z for the Centre for Respiratory Infection, an Imperial College and National Institute for Health Research Biomedical Research Centre funding scheme, a grant from Pfizer UK, and a European Respiratory Society fellowship (to M.C.). Spirometers were provided by Micro Medical Ltd, Rochester, UK. Author Disclosure: M.C. received advisory board fees from Chiesi Farmaceutici for $1,001–$5,000 and lecture fees from Boehringer Ingelheim and Merck Sharp & Dohme (for up to $1,000 each), AstraZeneca, and GlaxoSmithKline (for $1,001–$5,000 each). M.G.E. received a sponsored grant from FAMRI for more than $100,001. M.J. is a full-time employee of GlaxoSmithKline. S.J. received consultancy fees from AstraZeneca, Centocor, Sanofi-Pasteur, and Synairgen for $10,001–$50,000 each, and serves on the advisory board of AstraZeneca, Centocor, Sanofi-Pasteur, and Synairgen for $1,001–$5,000 each. S.J. received sponsored grants from AstraZeneca, Centocor, and Sanofi-Pasteur for more than $100,001, and from Synairgen for $50,001–$100,000. S.J. owns stock in Synairgen for $10,001–$50,000. O.M.K. served on the advisory board of Nycomed for less than $1,000. A.P. has received consultancy fees from Chiesi Farmaceutici for $5,001–$10,000, and from GlaxoSmithKline and AstraZeneca for $1,001–$5,000 each. A.P. served on the advisory board of Mundipharma, UCB, AstraZeneca, Nycomed, Italy, and GlaxoSmithKline for $1,001–$5,000 each, and Chiesi Farmaceutici for $5,001–$10,000. A.P. received lecture fees from Chiesi Farmaceutici for $10,001–$50,000, and from GlaxoSmithKline, AstraZeneca, Merck Sharp & Dohme, Boehringer Ingelheim, Novartis, Italy, and Pfizer for $1,001–$5,000 each. A.P. received sponsored grants from Chiesi Farmaceutici and Merck Sharp & Dohme for $10,001–$50,000 each, and from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline for $50,001–$100,000 each. V.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. V.L.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. K.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L. Slater does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L. Stanciu does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. This article has an online supplement, which is available from the issue's table of contents at www.atsjournals.org Originally Published in Press as DOI: 10.1164/rccm.201006-0833OC on October 1, 2010 |
| ISSN: | 1073-449X 1535-4970 1535-4970 |
| DOI: | 10.1164/rccm.201006-0833OC |