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Published ahead of print on September 22, 2005, doi:10.1164/rccm.200505-704OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 1, January 2006, 71-78

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Submitted on May 5, 2005
Accepted on September 21, 2005

Systemic, Upper and Lower Airway Inflammation at Exacerbation of COPD

John R Hurst1, Wayomi R Perera1, Tom M.A. Wilkinson1, Gavin C Donaldson1, and Jadwiga A Wedzicha1*

1 St. Bartholomew's Hospital, Academic Unit of Respiratory Medicine, London, United Kingdom

* To whom correspondence should be addressed. E-mail: j.a.wedzicha{at}medsch.ucl.ac.uk.

Rationale: In addition to pulmonary involvement, stable COPD is associated with nasal and systemic inflammation. While exacerbations of COPD are associated with increased pulmonary and systemic inflammation, determinants of the systemic response remain obscure, and nor is it known whether there is nasal involvement. Objectives: To investigate upper airway, lower airway, and systemic inflammation at exacerbation of COPD. Methods: We sampled sputum, nasal wash and serum from 41 exacerbations (East London cohort) for analysis of pathogenic microorganisms and inflammatory indices (sputum/ nasal wash leukocytes, interleukin (IL)6, IL8 and myeloperoxidase (MPO); serum IL6 and C-Reactive Protein (CRP)). Values were compared with stable COPD. Measurements and Main Results: Exacerbation of COPD is associated with greater nasal, sputum and serum inflammation than the stable state. At exacerbation, inflammatory markers were highly correlated within nasal wash and serum (all r≥0.62 p<0.001) but not sputum. The degree of upper airway inflammation correlated with the degree of lower airway inflammation (eg nasal wash/ sputum MPO, r=0.50, p=0.001). The degree of systemic inflammation correlated with the degree of lower airway inflammation (eg serum IL6/ sputum IL8, r=0.35, p=0.026), and was greater in the presence of a sputum bacterial pathogen (29.0g/dl CRP difference, p=0.002). We did not find relationships between the upper airway and systemic compartments. Conclusions: Exacerbation of COPD is associated with pan-airway inflammation; the systemic inflammatory response is proportional to that occurring in the lower airway and greater in the presence of a bacterial pathogen.
Key words: Nose, Pathogen, Cytokine




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