**1. Introduction**

Chronic obstructive pulmonary disease (COPD) is a disease which is characterized by airway inflammation and progressive airflow limitation with poor reversibility. Patients with COPD can experience periods of acute deterioration, which are called exacerbations. There are different definitions for an acute exacerbation of COPD (AECOPD). A symptom reported AECOPD is defined solely based on a patient's symptoms [1]. This is regardless of whether the patient seeks medical attention or receives treatment for the exacerbation. An event defined AECOPD requires a therapeutic intervention such as a change in COPD medications or a change in healthcare utilization [1]. Generally accepted is the definition as in the guidelines of the World Health Organization, US National Heart Lung and Blood Institute and Global Initiative for Chronic Obstructive Lung Disease (GOLD), which define an exacerbation as "an event in the natural course of the disease characterized by a change in the patient's baseline dyspnoea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset and may warrant a change in regular medication in a patient with COPD" [2]. Frequent exacerbations can result in a decreased health related quality of life [3], a decline in lung function [4], an increased risk of hospitalization [5] and an increase in mortality [6].

COPD and acute exacerbations of COPD (AECOPD) impose a burden on health care and so‐ ciety. It is estimated that COPD is the 4th leading cause of death worldwide and will be the 3rd leading cause of death in 2030 [7]. Along with increasing mortality rates, the loss in disa‐ bility-adjusted life years (DALYs) also rises. By 2030 COPD will be the 5th leading cause of loss in DALYs globally, where it was only number 13 in 2004. Increasing health care costs will be the consequence of this trend. In the European Union COPD accounts for just over 3% of the total health care budget. In the USA, the direct and indirect costs for COPD are

© 2013 Uzun et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

almost 50 billion USD. The majority of these costs are attributed to exacerbations [8]. The im‐ portance of exacerbations is reflected in the latest update of the GOLD report, in which the number of exacerbations in the preceding year is incorporated in the new classification of a patient with COPD [8]. In order to try to reduce the mortality, loss in DALYs and related costs and to lower the burden on society and health care, it is a goal to prevent and treat COPD and exacerbations of COPD. This chapter will give a concise overview of the back‐ ground of AECOPD and the available tools for its treatment and prevention.

induces inflammation and contributes to the progression of COPD [24, 25]. The existence of the chronic inflammation and oxidative stress is supported by the presence of oxidants and numerous pro-inflammatory cytokines in the airways and serum. Compared to healthy controls, sputum specimens of patients with stable COPD and AECOPD show increased numbers of neutrophils and increased levels of pro-inflammatory cytokines like interleukin-6 (IL-6) and interleukin-8 (IL-8) [21, 23, 26-29]. During an AECOPD neutrophils, IL-6 and IL-8 are also increased in serum [27, 30, 31]. Interleukin-6 is a cytokine released during initial immune response by different cell types of the native immune system, like macrophages. It induces hepatic acute phase response during inflammation [32] which in turn increases production of C-reactive protein (CRP). Interleukin-6 is also a growth factor for T- and B-cells [33]. Interleuking-8 is released by a variety of cell types involved in inflammation, like endothelial cells, fibroblasts and monocytes [34]. It is a potent neutrophil chemotactic and activating factor [34]. The presence of the increased inflammation in serum both during stable state and AECOPD may be explained by the "overspill theory", in which the local inflamma‐ tory processes in the lung "spill over" to the systemic circulation [35]. It is therefore thought that disease activity of COPD can be measured in serum by biomarkers. Exhaled breath condensate (EBC) components are thought to reflect the physiological state of lining fluid of the airways. It's a non-invasive mean of obtaining information on oxidative stress and inflammation in the airways. Hydrogen peroxide (H2O2, a precursor of potent oxidants OH and HOCl) and 8-isoprostane (formed by the free radical peroxidation of arachidonic acid) are EBC oxidative stress biomarkers proven to be elevated in patients with COPD during stable state and during exacerbations [31, 36-38]. Heme-oxygenase-1 (HO-1) is an inducible catalyzer of the degradation of heme to biliverdin which is thought to provide protection from oxidative stress. It is decreased in ex-smokers with COPD compared to control subjects [39] but increased during severe exacerbations [29], in healthy smokers and current smokers with COPD [40].

Acute Exacerbations of Chronic Obstructive Pulmonary Disease

http://dx.doi.org/10.5772/54867

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There is a great variety in reported infectious causes of COPD exacerbations. It is of importance to determine, both for bacteria and viruses, whether the presence of the microbe is actually the cause of the exacerbation. Estimated is that about 50-78% of acute exacerbations of COPD are caused by respiratory infections [24, 27, 41, 42], in which the clinical presentation range from pneumonia to coryzal symptoms with dyspnea. Patients with AECOPD of proven infectious aetiology have a longer hospital stay and a greater decrease in FEV1 than patients with non-

In the past viruses have been an underestimated cause of AECOPD and the causative role of viruses in AECOPD is still not fully established. The observation that as well viral infections and exacerbations are seasonal does suggest that viruses have a role in AECOPD [15, 43].

**4. Aetiology of AECOPD**

infective exacerbations [27].

**4.1. Microbiology**

**4.2. Viral causes**
