Aminophylline has been used for decades to treat both stable and acute COPD.
Its use however has reduced over the last few years due to a combination of lack of efficacy, development of new treatments and presence of significant side effects. It is now used as a treatment when despite the use of maximum inhaled bronchodilator therapy (triple therapy) the patient is still experiencing symptoms. It is also still commonly used to treat severe exacerbations of COPD but due to its narrow toxic to therapeutic ratio needs to be monitored regularly and used with caution. The main side effect is nausea and vomiting but these symptoms tend to reduce over a few weeks of use. Despite all of these problems we still find a number of patients who experience significant improvement in their symptoms with this drug. We recommend the use of a four-week trial of treatment, usually as Uniphyllin 200mg BD and then review the patient to assess their response.

Roflumilast is a novel new drug. It is a PDE4 inhibitor that works on immune and inflammatory cells, airway smooth muscle and pulmonary nerves. It is thought to work by inhibition, and suppresses the recruitment and activation of several inflammatory cells: neutrophils, CD8+ T cells, macrophages, and eosinophils. Common gastrointestinal side effects of nausea and diarrhoea have somewhat tempered the enthusiasm for this drug. It is a once daily oral agent. There have been 2 large studies in patients with COPD symptoms of bronchitis. It is licensed for COPD patients with an FEV1<50%, exacerbation in the last 12 months and a chronic bronchitic phenotype.

In the first study  Roflumilast was added to the long acting β2 agonist salmeterol or the long acting inhaled anti muscarinic tiotropium. The subjects had an FEV1 mean 50% predicted. Besides salmeterol or tiotropium, no inhaled corticosteroids, short acting anticholinergic drugs, other long acting bronchodilator drugs, theophylline, or other respiratory drugs were allowed after study enrolment. The results of these studies suggested that Roflumilast was beneficial, as assessed by improvement in lung function, even when added to a LABA or LAMA. COPD exacerbations rate in this study was reduced by 16-20%.

In the second study patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral Roflumilast or placebo for 52 weeks. Primary endpoints were change in pre bronchodilator FEV1 and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Patients were assigned to treatment and given Roflumilast (n=1537) or placebo (n=1554). Inhaled Corticosteroids and Long Acting Muscarinic Antagonists were banned during the study. FEV1 increased by 48 mL with Roflumilast compared with placebo (p<0·0001). The rate of exacerbations that were moderate or severe per patient per year was 1·14 with Roflumilast and 1·37 with placebo (reduction 17% [95% CI 8–25], p<0·0003). Adverse events were more common with Roflumilast (1040 [67%]) than with placebo Interpretation.

Our main concern in these studies was weight loss of around 2.5kg over a 12-month period. The drug is likely to be reserved for the severe and very severe COPD patient with frequent exacerbations and chronic sputum production.