Harnessing the Clinical Efficacy of Phosphodiesterase 4 Inhibitors in Inflammatory Lung Diseases: Dual-Selective Phosphodiesterase Inhibitors and Novel Combination Therapies - Phosphodiesterases as Drug Targets - page 435

with a history of frequent exacerbations as add-on to bronchodilator treatment ”
(Giembycz and Field 2010 ; Gross et al. 2010 ). However, gastrointestinal, psychiat-
ric, and oncological adverse are significant safety issues. In this chapter, we have
described several potential means by which the therapeutically beneficial actions of
PDE4 inhibitors could be realized without necessarily increasing the frequency of
adverse events. Thus, although a PDE4 inhibitor, roflumilast, has now reached
the market for the treatment of a subpopulation of patients with severe COPD
(Giembycz and Field 2010 ; Gross et al. 2010 ), the potential ability of these drugs to
enhance glucocorticoid action cannot be overstated. In this respect, it seems likely
that PDE4 inhibitors might, ultimately, be best exploited as part of a combination
therapy with ICSs and LABAs. The possibility that PDE inhibitors might be
developed for COPD (and possibly asthma) that target multiple enzyme families
is not an option that has obviously been embraced by the pharmaceutical industry.
Nonetheless, it is the opinion of the authors that such an approach could be
rewarding. Indeed, nonselective PDE inhibitors will target many components of
these multifactorial diseases at which selective PDE4 inhibitors alone do not.
Disclosures. The authors were solely responsible for the content and the writing of
the review. MAG has received honoraria, consultancy fees, and/or research grants
from AstraZeneca, Forest, Gilead Sciences, GlaxoSmithKline, Nycomed, Otsuka,
Proctor and Gamble, Sanofi-Aventis, Schering-Plough, and the GSK (Canada)/
Collaborative Innovation Research Fund. RN has received honoraria, consultancy
fees, and/or research grants from AstraZeneca, Gilead Sciences, GlaxoSmithKline,
Nycomed, Sanofi-Aventis, and the GSK (Canada)/Collaborative Innovation
Research Fund.
The authors declare no conflict of interest.
Acknowledgments RN is a Canadian Institutes of Health Research (CIHR) New Investigator
and an Alberta Heritage Foundation for Medical Research (AHFMR) Senior Scholar. Work in
the laboratories of RN and MAG is supported by CIHR operating grants (MOP 68828 and
MOP 93742, respectively) and educational research grants from AstraZeneca, Gilead Sciences,
GlaxoSmithKline, and Nycomed.
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