Asthma diagnosis and treatmentAre phosphodiesterase 4 inhibitors just more theophylline?
Section snippets
Theophylline
Since the first prescription of theophylline for the treatment of asthma in 1937, it has been widely used as an inexpensive oral treatment of both asthma and COPD.1 Traditional dogma has attributed the therapeutic effect of theophylline primarily to bronchodilatation, but at lower concentrations, it also possesses both immunomodulatory and anti-inflammatory actions, which are likely to contribute to some of the efficacy of the drug in treating patients with pulmonary disease.2
However,
Classification of PDEs
Eleven PDE families have now been identified by a variety of criteria, including substrate specificity, inhibitor potency, genetic makeup, and enzyme kinetics.11, 12 They act by hydrolyzing the phosphodiester bond of the second messengers cyclic nucleotides—cyclic 3′,5′ adenosine monophosphate (cAMP) and cyclic 3′,5′ guanosine monophosphate (cGMP), converting them to the inactive 5′ mononucleotides AMP and guanosine monophosphate, respectively.13 cAMP and cGMP are key second messengers in
PDE4: A therapeutic target in COPD and asthma
The PDE4 isoenzyme was identified as a major therapeutic target in respiratory diseases because it is the predominant isoenzyme in the majority of inflammatory cells, including neutrophils, which are implicated in the pathogenesis of COPD,16 and eosinophils, which characterize inflammation in asthma.17 PDE4 is also present alongside the PDE3 isoenzyme in airway smooth muscle; the PDE3 isoenzyme is considered to predominate in airway smooth muscle, and inhibition of this enzyme, rather than
Conclusion
Therapeutically, PDE4 inhibitors represent a novel class of orally active drugs for the treatment of respiratory disease, with no need to monitor plasma levels, reliable efficacy (even in current smokers), and fewer concerns from drug interactions, although the gastrointestinal side effects do give rise to some concerns regarding their use. However, given the positive effects of roflumilast in comparison with those of inhaled beclomethasone diproprionate,62 such drugs might be oral alternatives
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Disclosure of potential conflict of interest: C. Page has consultant arrangements with Johnson and Johnson, Glenmark Pharmaceuticals, and Altana; has stock in Rhinopharma; and is a speaker for Altana. V. Boswell-Smith has received grants from Altana. M. Cazzola has consultant arrangements with Altana; has received grants from Altana, AstraZeneca, and Chiesi Famaceutici; and is on the speakers' bureau for Altana, GlaxoSmithKline, Pfizer, Chiesi Famaceutici, Novartis, and Boehringer-Ingelheim.