Short-acting bronchodilators

• 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].
• NICE did not review the evidence of bronchodilators specifically in the acute setting. However, NICE did review evidence on delivery systems for bronchodilators during exacerbations. A meta-analysis of randomized controlled trials found hand-held inhalers with a spacer and nebulizers to be equally effective at alleviating symptoms. NICE acknowledged that in very breathless people, a nebulizer may be more appropriate.
• The example of doubling the dose or frequency is based on what CKS considers to be good clinical practice.

Systemic corticosteroids

• These recommendations are based on the NICE guideline on chronic obstructive pulmonary disease (COPD) [National Clinical Guideline Centre, 2010; NICE, 2010].
• NICE identified three systematic reviews and one subsequent randomized controlled trial of oral/systemic corticosteroids for COPD exacerbations, although they noted limitations to the validity and generalizability of several of the included studies. A significant effect was demonstrated in favour of oral/systemic corticosteroids over placebo for FEV₁ for at least 3 days, with some of the studies findings benefits for up to 5 days. Individual studies also found benefits in arterial PaO₂. Findings on the effect on duration of hospitalization were inconsistent, and no difference in mortality was demonstrated. People taking corticosteroids were more likely to have adverse effects (for example hyperglycaemia).
• Recommendations on the dose and duration of oral prednisolone are based on the expert opinion of the guideline development group, or on extrapolations from higher levels of evidence.

Antibiotics

• The recommendation on when to prescribe an antibiotic is based on the NICE COPD guideline [National Clinical Guideline Centre, 2010; NICE, 2010].
• NICE cited a meta-analysis of nine trials, which found a small but statistically significant effect favouring antibiotics over placebo in patients with exacerbations of COPD. Three studies found that the benefit from antibiotics was associated with the severity of the exacerbation; NICE based their recommendations on when to prescribe on their analyses of these studies.
• Recommendations on the appropriate regimens are based on the NICE COPD guideline [National Clinical Guideline Centre, 2010; NICE, 2010] and Management of infection guidance for primary care for consultation and local adaptation, developed by the Health Protection Agency and the Association of Medical Microbiologists [HPA and Association of Medical Microbiologists, 2010].
• NICE recommends that initial empirical treatment should be an aminopenicillin, a macrolide, or a tetracycline, and that guidance from local microbiologists should be taken into account [National Clinical Guideline Centre, 2010; NICE, 2010].
• The preference for amoxicillin or a tetracycline first-line, the choice of antibiotics, the dosages, and the recommendations on the use of co-amoxiclav are based on the Management of infection guidance for primary care [HPA and Association of Medical Microbiologists, 2010].