**4. Aetiology of AECOPD**

#### **4.1. Microbiology**

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‐

The prevalence of COPD varies greatly per country and also within countries [9]. This heterogeneity can be contributed to not only differences in diagnostic methods and classifica‐ tion but also to smoking habits, population age, in- and outdoor air pollution, occupational exposure, prevalence of pulmonary tuberculosis, chronic asthma and socioeconomic status [10]. Prevalences of COPD have been reported varying from 0,2-37% [11, 12]. The prevalence of AECOPD is very difficult to determine since there is no generally agreed definition for an AECOPD (see above). Studies show that only 32-50% of symptom defined AECOPD are reported by patients to health care professionals [13, 14]. Although there is no reliable estimate of the prevalence of AECOPD, much is known about the occurrence of exacerbations. Research shows that exacerbations are more frequent in the winter season [15] and may occur clustered in time [16]. Exacerbations are also more frequent and severe as COPD severity increases [17]. Besides COPD severity, the history of exacerbations is also a good predictor of future exacer‐ bations [17]. Furthermore, there is a strong correlation with symptoms of depression and

COPD is the result of a chronic inflammation in the airways. The inflammation is initiated by chronic exposure to exogenic toxins (e.g. cigarette smoke) which is causing damage to the airway epithelium and is activating the innate immune system giving a rapid, nonspecific response [20, 21]. Of the innate immune response the neutrophillic inflammation is most prominent in COPD. The cells of the innate immune system activate the adaptive immune system, of which CD8+-cells, CD4+ Thelper1 cells and B-cells have an important role in COPD. This activation of the adaptive immune response is the beginning of a cascade which causes extensive chronic inflammation, oxidative stress and remodeling, resulting in destruction of alveolar space and deposition of connective tissue in the subepithelium and adventitium of the airway wall [22]. The degree of chronic inflammation in COPD correlates with the severity of airflow limitation. This is supported by a correlation which is seen between the severity of obstruction and presence of CD8+-cells and B-cells in the small conducting airways [22] and the presence of neutrophils in sputum [23]. Also, bacterial colonization is more frequently observed in patients with severe to very severe COPD, suggesting that bacterial colonization

ground of AECOPD and the available tools for its treatment and prevention.

78 Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung

**2. Epidemiology**

recurrent exacerbations [18, 19].

**3. Pathophysiology of COPD and AECOPD**

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 noninfective exacerbations [27].

#### **4.2. Viral causes**

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]. Recently researchers deliberately exposed patients with COPD and healthy smokers to rhinoviruses and observed that this virus was able to cause an exacerbation in patients with COPD [44]. Detection of viruses by culture and by serology, where a second serum sample is also required, is less sensitive and more time consuming than PCR techniques, where only 1 sample is required. Because of the advanced PCR techniques in detecting viruses, the per‐ centage of exacerbations they account for can also be overestimated. The presence of viral DNA or RNA does not implicate that the virus is the cause of an exacerbation as several studies reported patients with stable COPD to carry viruses with percentages varying from 12-19% [45, 46]. In exacerbations several studies have reported that viruses were detected in 20-56% of cases [24, 27, 41, 42, 46, 47]. In these studies rhinovirus, influenza virus and respiratory syncytial virus and were the most common isolated viruses. A more extensive overview can be found in table 1.

**4.3. Bacterial causes**

**4.4. Non-microbial causes**

**5.1. History**

**5.2. Laboratory tests**

ly compensate the hypercapnia.

acquisition of a new strain is linked to an exacerbation.

about 30% of exacerbations are of unknown origin [6].

**5. Clinical Presentation and Diagnosis**

Bacteria as cause of AECOPD are reported from 30% [48] up to 55% [27, 49]. The most common bacterial pathogens are *Streptococcus pneumoniae*, *Haemophilus influenzae*, *Moraxella catarrhalis* and in patients with more severe COPD also *Pseudomonas aeruginosa* [42, 48]. It is difficult to determine the role of bacteria in AECOPD, as 34-48% of patients with COPD are reported to be colonized with bacteria [26, 27, 50, 51]. Molecular typing of bacteria during exacerbations showed that the acquisition of new strains may cause exacerbations [52], but not every

Acute Exacerbations of Chronic Obstructive Pulmonary Disease

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

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One tenth of AECOPD are due to environmental pollution, of which ozone, sulphur dioxide and nitrogen dioxide known and researched causes [53, 54]. Particulate matter (PM) is also related to increased admissions for COPD and other respiratory diseases [53, 55]. Particulate matter consists of a mixture of solid particles and liquid aerosols suspended in the air from natural sources, industrial activities and can also be traffic related [56]. Other possible, noninfectious causes may be left sided heart failure, change in environmental temperature, but

Patients with an AECOPD usually present with dyspnea, which may be acute but can also be a history of slowly progressive dyspnea. Coughing or sputum production may or may not be present. When expectorating sputum, it is important to assess whether sputum volume has increased and whether it is purulent (e.g. green). Purulent sputum is usually a sign of infection [57]. Fever or other signs of infection should be looked for. Hemoptysis may be present in case

Laboratory test can be performed if necessary. C-reactive protein as marker for inflamma‐ tion can be performed. Additional laboratory tests can be performed depending on the differential diagnosis. If available, an arterial blood gas can be performed. Hypoxemia may be present and in more severe cases a patient can also retain CO2. Hypercapnia is defined as arterial blood gas CO2 (*P*aCO2) level above 45 mmHg (6,00 kPa) and hypercapnic respiratory failure as *P*aCO2 of >50 mmHg (6,67 kPa). When present it is important to assess if the hypercapnia is longer existing and to assess if the patient is being able to metabolical‐

of a severe infection. Risk factors for atypical infections should be thought of.


**Table 1.** Most common causes of exacerbations of COPD.
