How phosphodiesterase 4 inhibitors work in patients with chronic obstructive pulmonary disease of the severe, bronchitic, frequent exacerbator phenotype.

Current international guidelines recommend that roflumilast be added on to an inhaled corticosteroid/long-acting β2-adrenoceptor agonist (LABA) combination therapy in high-risk patients with severe, bronchitic chronic obstructive pulmonary disease who have frequent acute exacerbations. This article presents evidence that a glucocorticoid, LABA, and phosphodiesterase (PDE) 4 inhibitor in combination can interact in a complex manner to induce a panel of genes that could act collectively to suppress inflammation and improve lung function. The possibility that multivalent ligands may deliver superior efficacy is also being explored. Single molecules that inhibit PDE4 and activate β2-adrenoceptors at similar concentrations have been described.