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Systemic and Upper and Lower Airway Inflammation at Exacerbation of Chronic Obstructive Pulmonary Disease

Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, London, United Kingdom

Correspondence and requests for reprints should be addressed to Jadwiga A. Wedzicha, M.D., F.R.C.P., Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, Royal Free Hospital London NW3 2PF UK. E-mail: j.a.wedzicha{at}medsch.ucl.ac.uk

Rationale: In addition to pulmonary involvement, stable chronic obstructive pulmonary disease (COPD) is associated with nasal and systemic inflammation. Although 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, IL-8, and myeloperoxidase; serum IL-6 and C-reactive protein). 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 (e.g., nasal wash/sputum myeloperoxidase; r = 0.50, p = 0.001). The degree of systemic inflammation correlated with the degree of lower airway inflammation (e.g., serum IL-6/sputum IL-8; r = 0.35, p = 0.026), and was greater in the presence of a sputum bacterial pathogen (29.0 g/dl C-reactive protein 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: cytokine • nose • pathogen

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