**7.2. Long-acting bronchodilators**

patients with self-reported purulent sputum and withheld in patients with non-purulent sputum [71]. There was no difference between the two groups in treatment failure on day 3, suggesting patient reported non-purulent sputum may be a valid criterion to withhold antibiotics [71]. A Dutch study showed that addition of doxycycline to the treatment regimen with glucocorticoids of a patient with an exacerbation was superior on day 10 but equivalent on day 30 in terms of clinical success and clinical cure compared to glucocorticoids alone, even in patients not showing signs of infection [72]. Most recently Spanish investigators performed a multicenter trial where they suggested that treatment of a mild to moderate exacerbation with amoxicillin/clavulanate, independent of glucocorticoids treatment, might give better clinical cure after 10 days compared to placebo [73]. In this study the median time to next exacerbation was also increased in patients receiving antibiotics compared to placebo. Unfortunately, because of recruitment problems this study did not reach the calculated amount of patients needed, so that definite conclusions cannot be made from the results of this study.

**Presence of symptoms and findings**



Increased sputum volume Increased sputum purulence


Preventing exacerbations is an important treatment goal in COPD. There is a wide range of preventive measures which have proven to reduce exacerbation frequency or hospitalization

Influenza vaccination and pneumococcal vaccination have both been researched as preventive measures for infection associated exacerbations. Current GOLD guidelines [8] advise influenza vaccination for patients with COPD. Pneumococcal vaccination is mainly advised for elderly

Type 3 1 of three symptoms of type 1, plus at least one of the following findings:

past 5 days

baseline

**Table 2.** Classification of acute exacerbations of COPD according to Anthonisen criteria [70]

**Classification of AECOPD according to**

Type 1 Increased dyspnea

84 Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung

Type 2 Two symptoms of type 1

**Anthonisen criteria**

**7. Prevention**

in patients with AECOPD.

**7.1. Supportive measures**

Long-acting bronchodilators can be divided in two groups: long acting muscarinic receptor antagonists (LAMAs) and long acting β-agonists (LABAs). Both have proven to show a positive effect on exacerbation reduction and improvement in quality of life [75-79]. An overview of the long-acting bronchodilators is given in table 3.


**Table 3.** An overview of available long-acting bronchodilators.

Of the long-acting bronchodilators, indacaterol and glycopyrronium are the most recent additions for the treatment of COPD. Indacaterol is proven to be superior to formoterol, salmeterol and tiotropium in terms of use of rescue medication, dyspnoea score and health related quality of life. Compared to salmeterol and formoterol it is also superior in improving spirometry values. Indacaterol is non-inferior to tiotropium but when added to tiotropium therapy it is superior compared to tiotropium alone [80]. Indacaterol also lowers the risk of AECOPD compared to placebo [78, 81, 82]. Glycopyrronium has been approved in 2012 as therapy for COPD. It provides significant improvements in lung function, dyspnoea, health status, exacerbation frequency and rescue medication use versus placebo, and is comparable to tiotropium [83, 84]. The combination of glycopyrronium and indacaterol has shown superiority in bronchodilation compared to indacaterol alone [85]. Glycopyrronium has not been compared to other LABAs yet.

## **7.3. Inhalation corticosteroids**

Inhalation corticosteroids (ICS) can be given to patients with high risk of exacerbations. In several studies ICS provided a reduction of symptoms (dyspnea, cough) and reduced the frequency of exacerbations [86-88]. The GOLD guidelines advise treatment for high exacerba‐ tion risk patients with few symptoms (group C) with a combination of ICS/LABA or a LAMA alone, or a combination of LABA and LAMA [8]. For high exacerbation risk patients who have many symptoms (group D) the same treatment is advised as for group C, also a combination of all three classes of inhalation drugs is possible [8].
