0503. More on theophylline and its role in asthma

As mentioned in the first of this year's summaries, interest in theophylline is being rekindled as its range and mechanisms of actions are becoming clearer. Although identified in our South African 'MIMS' reference of prescription medicines as a bronchodilator, theophylline is regarded as a weak dilator when compared against ß2 agonists and ipratropium bromide. Some studies have suggested that combination with other bronchodilators merely increases side effects without improving airway patency. However, concentrating on dilatation alone may be too restrictive in terms of theophylline's many other actions. Current opinion is that theophylline acts also to decrease the inflammatory component of the late asthmatic phase. This action is due to the drug's inhibitory effects on phosphodiesterase type 4 (PDE4) and is via cyclic AMP increases. PDE4 is ubiquitous among inflammatory and immune cells, and inhibitors show suppressive activity on various in-vitro responses including cytokine production, cell proliferation, chemotaxis, release of inflammatory mediators, and NAPDH-oxidase activity. Further work has now broken PDE4 down to sub-types, with PDE4B being the receptor to target for inhibition of the inflammatory responses. Two drugs that are currently being reviewed for effectiveness as PDE4B inhibitors, cilomilast and roflumilast, may prove to provide the desired effects of methyl xanthines without the toxicity that is observed with theophylline because of its narrow therapeutic range.

Read more:
Lancet 2004;365:167-75
Ann Intern Med 1993;119:1216-7
J Allergy Clin immunol 1986;78:780-7