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Published ahead of print on February 16, 2006, doi:10.1164/rccm.200506-859OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 10, May 2006, 1114-1121

A more recent version of this article appeared on May 15, 2006
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Submitted on June 3, 2005
Accepted on February 16, 2006

Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations

Alberto Papi1, Cinzia Maria Bellettato2, Fausto Braccioni1, Micaela Romagnoli3, Paolo Casolari1, Gaetano Caramori1, Leonardo M Fabbri3*, and Sebastian L Johnston4

1 Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy, 2 Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; Imperial College London, National Heart and Lung Institute, London, United Kingdom, 3 Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; Section of Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy, 4 Imperial College London, National Heart and Lung Institute, London, United Kingdom

* To whom correspondence should be addressed. E-mail: fabbri.leonardo{at}unimore.it.

Rationale. Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalisation. The role of infections in COPD exacerbations is controversial. Objectives. We investigated whether COPD exacerbations requiring hospitalisation are associated with viral and/or bacterial infection and evaluated relationships between infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. Methods. We examined 64 COPD patients when hospitalised for exacerbations, and when in stable convalescence. We measured lung function, blood gases, exhaled nitric oxide and examined sputum for inflammation and for viral and bacterial infection. Results. Exacerbations were associated with impaired lung function (P<0.01) and increased sputum neutrophilia (P<0.001). Viral and/or bacterial infection was detected in 78% of exacerbations - viruses in 48.4% (6.2% when stable, P<0.001), bacteria in 54.7% (37.5% when stable, P=0.08). Infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial co-infection) had longer hospitalisations (P<0.02) and greater impairment of several measures of lung function (all P<0.05) than non-infectious exacerbations. Exacerbations with co-infection had more marked lung function impairment (P<0.02) and longer hospitalisations (P=0.001). Sputum neutrophils were increased in all exacerbations (P<0.001), and related to their severity (P<0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (P<0.001) virus associated exacerbations. Conclusions. Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial co-infection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.
Key words: COPD, severe exacerbations, respiratory viruses, bacteria, airway inflammation




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