BACKGROUND A common pathological feature of chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) is mucus hypersecretion. MUC5AC is the predominant mucin gene expressed in healthy airways and is increased in asthmatic and COPD patients. Recent clinical trials indicate that phosphodiesterase type 4 (PDE4) inhibitors may have therapeutic value for C...

Retinoic acid decreases proteinuria and glomerulosclerosis in several animal models of kidney disease by protecting podocytes from injury. Our recent in vitro studies suggest that all-trans retinoic acid induces podocyte differentiation by activating the retinoic acid receptor-α (RARα)/cAMP/PKA/CREB pathway. When used in combination with all-trans retinoic acid, an inhibitor of phosphodiesteras...

Background: Chronic obstructive pulmonary disease is the leading cause morbidity and mortality worldwide. Cigarette smoke noxious agent causing oxidative stress activated nuclear factor-κB then increase inflammatory cell releases. Roflumilast have antiiinflammatory effect which can be use as addition therapy for stable COPD.Methods: The pretest postest experimental clinical trial was carried ou...

10.2217/14750708.4.2.153 © 2 Isoenzyme phosphodiesterase 4 inhibitors are novel therapeutic agents in late clinical development for the treatment of chronic obstructive pulmonary disease and asthma, both diseases with significant unmet treatment needs. Roflumilast is one such isoenzyme phosphodiesterase 4 inhibitor that is undergoing Phase III clinical development. It is an orally active compou...

In this issue of CHEST (see page 758), White et al 1 report signifi cantly lower major adverse cardiovascular events (MACEs) for rofl umilast compared with placebo (hazard ratio, 0.65; 95% CI, 0.45-0.93; P 5 .019) from data in 12,054 patients with COPD. In addition to the studies analyzed not being designed or powered to examine cardiovascular outcomes, we would like to point out other limitati...

The United States Food and Drug Administration recently approved the third dermatological phosphodiesterase-4 (PDE4) inhibitor, roflumilast, for topical treatment of psoriasis. It is more potent effective than its two predecessors, apremilast crisaborole. All 3 are rationally designed PDE4 inhibitors with in vitro inhibitory constant IC50 of: 0.14 μM (apremilast), 0.24 (crisaborole), 0.7 nM (ro...

BACKGROUND In this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD). METHODS Mice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral i...

Background: A common pathological feature of chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) is mucus hypersecretion. MUC5AC is the predominant mucin gene expressed in healthy airways and is increased in asthmatic and COPD patients. Recent clinical trials indicate that phosphodiesterase type 4 (PDE4) inhibitors may have therapeutic value for ...

ASP3258 is a potent and selective PDE4 inhibitor and exerts a wide-range of anti-inflammatory effects with low emetic potential, a major adverse effect of PDE4 inhibitors. Here, we investigated the anti-asthmatic potency of ASP3258 as compared with those of two representative PDE4 inhibitors: roflumilast and cilomilast. Orally administered ASP3258, roflumilast, and cilomilast all inhibited oval...