These recommendations are based on the National Institute for Health and Clinical Excellence (NICE) clinical guideline Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update) [National Clinical Guideline Centre, 2010; NICE, 2010].

• Short-acting bronchodilators compared with placebo
• The evidence for short-acting bronchodilators compared with placebo in chronic obstructive pulmonary disease (COPD) is mainly from small, short-term randomized controlled trials. However, results show a short-term improvement in breathlessness, quality of life, and lung function.
• Long-acting beta-2 agonists (LABAs) compared with placebo
• The evidence suggests a general improvement in lung function, quality of life, and symptoms, and a reduction of exacerbation rates, when LABAs are compared with placebo.
• Long-acting muscarinic antagonists (LAMAs) compared with placebo
• The evidence suggests that LAMAs are superior to placebo in reduction of exacerbation rates. There was also a general improvement in lung function, quality of life, and symptoms in people with COPD treated with LAMAs compared with placebo.
• LAMAs compared with a short-acting muscarinic antagonists (SAMA)
• The evidence suggests an improvement in quality of life and symptoms, and reduction of exacerbation rates, when long-acting bronchodilators are compared with a SAMA (ipratropium bromide). Cost-utility studies (with limitations) comparing treatment with tiotropium and ipratropium in people with stable COPD show that once-daily tiotropium is more cost effective and may improve adherence.
• LABAs compared with LAMAs
• The evidence shows that LABAs and LAMAs are similar in improving quality of life and symptoms. Nevertheless, a LAMA (tiotropium) seems to be slightly better at reducing exacerbation rates and improving lung function compared with LABAs (salmeterol and formoterol). NICE suggests that both classes are equally effective for initial maintenance bronchodilator therapy in people with COPD whose forced expiratory volume in 1 second (FEV₁) is 50% or greater.
• Inhaled corticosteroids (ICS) as monotherapy
• In the updated COPD guideline, NICE no longer makes any specific recommendations on the use of ICS as monotherapy in people with COPD.
• The recommendation to avoid the use of ICS as monotherapy in COPD is based on evidence from a systematic review that ICS alone has no effect on exacerbation rates in people with mild COPD (defined as FEV₁ greater than 50%), and that there is no significant difference in mortality between ICS (when used as monotherapy) and placebo.
• Furthermore, there are no preparations containing only ICS that are licensed for use in COPD in the UK. The Medicines and Healthcare products Regulatory Agency recommends that ICS should not be used alone in COPD [MHRA, 2009]. They undertook a literature review of published and unpublished trials which found LABA plus ICS combinations to have greater efficacy than either LABAs or ICS alone in every study.
• LABA plus ICS compared with LABAs alone
• There is evidence to suggest that overall, compared with LABAs alone, people with COPD taking LABAs plus ICS have a significant increase in post-dose FEV₁, and improvement in health-related quality of life. They also have fewer exacerbations. Economic studies found that LABA plus ICS is more cost effective than LABA alone in people with COPD with FEV₁ less than 50% predicted.
• LABA plus ICS plus LAMA (triple therapy) compared with LABA plus LAMA
• The evidence shows that there is no significant difference between triple therapy (tiotropium plus fluticasone plus salmeterol) and tiotropium plus salmeterol in clinical outcome (breathlessness, exacerbation, mortality, pneumonia, myocardial infarction, or acute arrhythmia) in people with moderate to severe COPD. A cost-effectiveness study found triple therapy not to be more cost effective than LAMA plus LABA.