There is ongoing debate about the role of ICS in patients with COPD. The potential benefits of ICS must be balanced against the potential risks including local oropharyngeal adverse effects and pneumonia. A meta-analysis of 43 studies of COPD showed an increased risk of pneumonia with ICS use, but this was balanced against the benefit of reduced exacerbations.20 Their main impact is to reduce the risk of exacerbations; in contrast to long-acting bronchodilators their effects on symptoms and lung function are small and often insufficient to use as a guide to treatment efficacy.
Treatment with ICS is directed at patients deemed to be at risk of exacerbations because of a past history of exacerbations and/or poor lung function.21 There is emerging evidence that blood eosinophil counts may be a useful biomarker of ICS response in patients with COPD.22 Those with blood eosinophil counts less than 100 cells/mcL appear less likely to benefit from ICS, and those with a count of more than 300 cells/mcL are more likely to benefit. ICS inhalers alone are not indicated for COPD; the combination of an ICS and a LABA is used in COPD as this works better than an ICS inhaler alone.
A reasonable approach based on current evidence is to consider the addition of ICS to long-term maintenance bronchodilator therapy in patients with COPD and a history of multiple or severe exacerbations and poor lung function (FEV1 <50% predicted), particularly if blood eosinophil counts are more than 300 cells/mcL, and in those with COPD and asthma. The risk of pneumonia is higher in patients of older age, with a lower body mass index (BMI), with greater general fragility and who are receiving higher ICS doses, and possibly in those with blood eosinophil counts less than 100 cells/mcL.22 Patients should be educated that if they develop a chest infection they should receive antibiotic treatment promptly. Comorbidities, especially osteoporosis and diabetes mellitus, should also be taken into account.
In general, the use of drugs in COPD does not involve back titration. The exception is when oral corticosteroids have been given for an exacerbation. Additionally, in light of recent trials, in patients with COPD with no evidence of asthma and with infrequent exacerbations ICS withdrawal can be considered.10 Close monitoring is advised after withdrawal, and withdrawal should be considered cautiously in those with elevated blood eosinophil counts and/or poor lung function.
Long-term use of systemic corticosteroids is not recommended in patients with COPD due to an unfavourable risk-benefit ratio.10 However, short-term use to treat exacerbations is supported by good-quality evidence, with reduction in the severity of exacerbations, shortened recovery times and reduced hospital admissions and readmissions being noted.10
Several recent trials of monoclonal antibodies targeting interleukin-5 to reduce eosinophil activity have suggested that biologic therapies may have value in the treatment of patients with COPD and eosinophilia.23 Further prospective trials are awaited. Phosphodiesterase type-4 inhibitors are potential candidates for the treatment of COPD, but this class of medications is currently not available in Australia.
Several trials have suggested that in patients with moderate-to-severe COPD and frequent exacerbations, long-term treatment with oral macrolides may reduce the frequency of exacerbations. However, owing to the potential significant adverse effects including cardiac toxicity, ototoxicity, diarrhoea and antibiotic resistance it is recommended that specialist advice be sought if this therapy is being considered.24 There is no evidence base to support long-term use of other antibiotics.
Theophylline has a modest bronchodilator effect, but is not currently recommended in Australia. This is because of its narrow therapeutic index, its potential for significant side effects and the lack of demonstration of a reduction in exacerbation rates in patients who are on adequate inhaled therapy.25