Montuschi also reduce the rate of COPD exacerbations compared with placebo (Rabe et al 2005; Rennard et al 2006). The effect of PDE4 inhibitors on health status in patients with COPD is variable possibly due to differences in the duration of treatment (Compton et al 2001; Rabe et al 2005; Rennard et al 2006). Cilomilast at a dose of 15 mg twice daily for 12 weeks reduces CD4+ T-lymphocyte subsets and CD68+ macrophages in bronchial biopsies from patients with COPD (Gamble et al 2003). However, whether these changes in air- way inﬂammation are related to clinical outcomes in patients with COPD is unknown (Lipworth 2005). The main adverse effects of PDE4 inhibitors are nausea, diarrhea, and abdomi- nal pain (Lipworth 2005). Roﬂumilast is more tolerated than cilomilast as it has similar selectivity for PDE4 isoenzymes, whereas cilomilast is 10 times more selective for PDE4D than other isoenzymes (Manning et al 1999; Hatzelmann and Schudt 2001). Long-term studies are required to deﬁnitively establish the effects of PDE4 inhibitors on clinical outcomes, including lung function, exacerbation rate, and health status in patients with COPD. Treatment of exacerbations of COPD According to a recent deﬁnition, exacerbations of COPD are “a variation in symptoms above the normal day to day variation which causes a change in a patient’s medica- tion” (Rodriguez-Roisin 2000). Exacerbations of COPD worsen general health status (Seemungal et al 1998) and are considerably expensive. The number of exacerbations is related to disease severity. Patients with moderate to severe COPD have one or two exacerbations per year (Seemungal et al 1998; Burge et al 2000). Many factors determine the type of treatment used and where the treatment is carried out, for example, in an outpatient or hospital setting. The severity of the exacerbations is related to the severity of the disease. In patients with mild COPD, exacerbations are associated with increased breathlessness accompanied by cough and sputum production. They may often be managed out of hospital. Exacerbations of severe COPD are often associated with respiratory failure which may be fatal and require hospital admission on a general ward or intensive care unit. Exacerbations are caused by bacterial or viral infections in around 50% of cases (Monso et al 1995; Soler et al 1998; Seemungal et al 2000). Other factors such as air pollution and temperature may cause exacerbations (MacNee 2002). However, it is not possible to identify a cause in about one third of exacerbations of COPD (Connors et al 1996). One of the main problems is the decision to treat exacerbations of COPD at home or in hospital. This decision is inﬂuenced by 418 the severity of symptoms, the severity of COPD, and whether hospital admission is required. Recent trials have shown that about 30% of patients admitted to hospital with exacerbations of COPD could be adequately treated at home with immediate or early discharge and nurse-led home care (Skwarska et al 2000; Cotton et al 2000; Davies et al 1999, 2000). Patients prefer this form of treatment, which has been widely adapted to facilitate the discharge of those patients initially requiring hospitalization (Cotton et al 2000; Ojoo et al 2002). However, a clinical trial showed that home care did not improve the health of the patients whilst increasing costs compared with admission to hospital (Shepperd, Harwood, Gray, et al 1998; Shepperd, Harwood, Jenkinson, et al 1998). Home treatment The algorithm shown in Figure 3, which is based on a stepwise therapeutic approach (Sachs 1981; ATS 1995; Siafakas et al 1995; Celli 1996; Shepperd, Harwood, Jenkinson, et al 1998), may be used in the home treatment of exacerbations of COPD using bronchodilators, if necessary delivered by nebulizer, or antibiotics if symptoms indicate a bacterial infection, and oral glucocorticoids in moderate to severe exacerbations. The dose and/or frequency of bronchodilator delivery must be increased or bronchodilator treatment must be started if these drugs have not been used previously. Administration of high doses of antimuscarinics on demand delivered for a number of days using a nebulizer may be useful, even though chronic nebulizer treatment is not generally recommended after an exacerbation (GICOPD 2001). Systemic glucocorticoids are effective for exacerbations of COPD as they facilitate clinical improvement and lung function (Thompson et al 1996; Niewoehner et al 1999; Cotton et al 2000) and are recommended for patients with moderate to severe exacer- bations of COPD when the baseline FEV1 is less than 50% of the predicted value (GICOPD 2001). The optimum dose and duration of treatment is not known, but administration of oral prednisolone at 40mg per day for ten days is gener- ally effective (GICOPD 2001). Nebulized budesonide is as effective as oral glucocorticoids in improving lung function. However, it is not clear whether the increased costs of inhaled glucocorticoids are justiﬁed in all cases (Maltais et al 2002). Antibiotic treatment, which does not generally require parenteral administration, is recommended if two or more of the following symptoms are present: increasing dyspnoea, increasing sputum purulence, or increasing sputum volume (Anthonisen et al 1987). Antibiotics should be chosen which are effective against Streptococcus pneumoniae, Haemophilus inﬂuenzae, and Moraxella catarrhalis. These International Journal of COPD 2006:1(4)