**4.3. Bacterial causes**

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.

**Bacteria**

**Viruses**

**Other**

**COPD exacerbations: divided by cause**

Human rhinovirus Respiratory syncytial virus

Influenza virus Parainfluenza virus Human metapneuvirus

Coronavirus Adenovirus **Atypical microorganisms**

> *Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella pneumophila Coxiella burnetii*

Sulphur dioxide (SO2)

Nitrogen dioxide (NO2)

Particulate matter (PM2,5 , PM10)

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

Ozone (O3)

*Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Haemophilus parainfluenzae Pseudomonas aeruginosa Staphylococcus aureus*

80 Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung

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 acquisition of a new strain is linked to an exacerbation.

#### **4.4. Non-microbial causes**

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