These recommendations are mainly 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 people with 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 compared with placebo.
• 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 short-acting muscarinic antagonists (SAMAs)
• The evidence suggests an improvement in quality of life and symptoms, and reduction of exacerbation rates when LAMAs are compared with 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.
• 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.
• Although there is evidence from a systematic review that ICS reduce the exacerbation rate by 25% compared with placebo in people with more severe COPD (mean forced expiratory volume in 1 second [FEV₁] less than 50% predicted), there was no significant difference in mortality. More important, the Medicines and Healthcare products Regulatory Agency undertook a literature review of published and unpublished trials which found LABA plus ICS combinations to have greater efficacy than either LABA or ICS alone in every study, and they recommend that ICS should not be used alone in COPD [MHRA, 2009].
• There are no preparations containing only ICS that are licensed for use in COPD in the UK.
• LABA plus ICS compared with LABA alone
• There is evidence to suggest that overall, compared with LABAs alone, people with COPD taking LABA 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 show that LABA plus ICS is more cost-effective than LABA alone in people with COPD whose FEV₁ is less than 50% predicted.
• LABA plus ICS compared with LAMA alone
• The evidence suggests a small and clinically insignificant improvement in quality of life in people with COPD (FEV₁ less than 50%) on LABA plus ICS, compared with LAMA alone. Exacerbation rates were similar between the two groups and were not clinically significant.
• There is no evidence to favour LAMA plus ICS over LAMA alone or vice versa. Either regimen can be used for initial maintenance treatment in people with COPD whose FEV₁ is less than 50% [National Clinical Guideline Centre, 2010].
• LABA plus ICS plus LAMA (triple therapy) compared with LABA plus ICS and LAMA alone
• Evidence suggests that LABA plus ICS or LAMA alone is more cost effective than triple therapy. However, triple therapy is more effective (highest quality-adjusted life-years). Owing to the limitations of the studies, NICE concluded that LABA plus ICS or LAMA alone should be offered as initial maintenance treatment to people with COPD whose FEV₁ is less than 50%.
• Triple therapy is recommended if symptoms or exacerbations persist because it is more effective in terms of exacerbation reduction and symptom relief [National Clinical Guideline Centre, 2010].