PDE4 inhibitors in COPD--a more selective approach to treatment

Respir Med. 2004 Jun;98(6):495-503. doi: 10.1016/j.rmed.2003.12.012.


Chronic obstructive pulmonary disease (COPD) is a serious and mounting global public health problem. Although its pathogenesis is incompletely understood, chronic inflammation plays an important part and so new therapies with a novel anti-inflammatory mechanism of action may be of benefit in the treatment of COPD. Cilomilast and roflumilast are potent and selective phosphodiesterase (PDE)4 inhibitors, with an improved therapeutic index compared with the weak, non-selective PDE inhibitor, theophylline. Unlike theophylline, which is limited by poor efficacy and an unfavourable safety and tolerability profile, the selective PDE4 inhibitors are generally well tolerated, with demonstrated efficacy in improving lung function, decreasing the rate of exacerbations and improving quality of life, with proven anti-inflammatory effects in patients with COPD. Theophylline is a difficult drug to use clinically, requiring careful titration and routine plasma monitoring due to the risk of toxic side effects, such as cardiovascular and central nervous system adverse events, with dose adjustments required in many patients, including smokers, the elderly and some patients on concomitant medications. In contrast, the selective PDE4 inhibitors are convenient medications for both patient and physician alike. Hence these agents represent a therapeutic advance in the treatment of COPD, due to their novel mechanism of action and potent anti-inflammatory effects, coupled with a good safety and tolerability profile.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Aminopyridines / therapeutic use
  • Benzamides / therapeutic use
  • Bronchodilator Agents / therapeutic use
  • Carboxylic Acids
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclohexanecarboxylic Acids
  • Cyclopropanes
  • Humans
  • Nitriles
  • Phosphodiesterase Inhibitors / pharmacokinetics
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pneumonia / complications
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Rolipram / therapeutic use
  • Theophylline / pharmacokinetics
  • Theophylline / pharmacology
  • Theophylline / therapeutic use
  • Treatment Outcome


  • Aminopyridines
  • Benzamides
  • Bronchodilator Agents
  • Carboxylic Acids
  • Cyclohexanecarboxylic Acids
  • Cyclopropanes
  • Nitriles
  • Phosphodiesterase Inhibitors
  • Roflumilast
  • Cilomilast
  • Theophylline
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Rolipram