PDE4A and chronic bronchitis: Roflumilast, the most advanced of PDE4 inhibitors, has been recently approved by the European Medicines Agency (EMA) for the maintenance treatment of severe COPD disease (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment.