Airways inflammation and treatment during acute exacerbations of COPD

Abstract

Introduction: Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations. It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation.

Objectives: To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations. To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations. To speculate on future therapeutic options to modify inflammation during COPD exacerbations.

Results: During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes. Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive.

Conclusion: Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations. This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects.

Figure 1

An increase in neutrophils concurs with a drop in FEV₁ during a COPD exacerbation. Data of 64 patients. Copyright © 2006. Reproduced with permission from from Papi A, Bellettato CM, Braccioni F et al 2006. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med, 173:1114–21. Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in one second.

Figure 2

Changes in sputum eosinophil numbers from stable phase of COPD to the onset of an exacerbation. Copyright © 2005. Reproduced with permission Fujimoto K, Yasuo M, Urushibata K et al 2005. Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease. Eur Respir J, 25:640–6. Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 3

Lymphocytes are involved in the onset of COPD exacerbations. CD8+ cells are increased at COPD exacerbations, causing a decreased CD4/CD8 ratio. Copyright © 2005. Reproduced with permission from Tsoumakidou M, Tzanakis N, Chrysofakis G et al 2005a. Changes in sputum T-lymphocyte subpopulations at the onset of severe exacerbations of chronic obstructive pulmonary disease. Respir Med, 99:572–9. Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 4

In an aero-allergen induced allergic inflammation mice model, inhaled carbon monoxide (CO) reduced inflammatory cell counts (×104/mL) in broncho-alveolar lavage fluid. Treated animals (CO) received 250 parts per million inhaled carbon monoxide 2 hours before the aero-allergen challenge (OVA) and continuously thereafter. Control animals were kept in room air (RA) for the duration of the experiment. Copyright © 2001. Reproduced with permission from Chapman JT, Otterbein LE, Elias JA et al 2001. Carbon monoxide attenuates aeroallergen-induced inflammation in mice. Am J Physiol Lung Cell Mol Physiol, 281:L209–L216. Notes: *Significantly increased (p < 0.05) from sham-challenged animals; †Significantly different (p < 0.05) from mice kept in room air; ††Significantly different (p < 0.0007) from mice kept in room air.