期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 183, 期 6, 页码 734-742出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201006-0833OC
关键词
disease exacerbation; respiratory tract infections; COPD; rhinovirus
资金
- GlaxoSmithKline
- Medical Research Council
- British Medical Association
- British Lung Foundation/Severin Wunderman Family Foundation [P00/2]
- Wellcome Trust [083567/Z/07/Z]
- Imperial College
- National Institute for Health Research Biomedical Research Centre funding scheme
- Pfizer UK
- European Respiratory Society fellowship
- Chiesi Farmaceutici
- Boehringer Ingelheim
- Merck Sharp Ex Dohme
- AstraZeneca
- FAMRI
- Centocor
- Sanofi-Pasteur
- Synairgen
- Merck Sharp Dohme
- Novartis, Italy
- Pfizer
- Wellcome Trust [083567/Z/07/Z] Funding Source: Wellcome Trust
- Medical Research Council [G1000758, G1000758B] Funding Source: researchfish
- National Institute for Health Research [CL-2008-21-014] Funding Source: researchfish
Rationale: 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. Objectives: 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. Measurements and Main 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.
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