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Phosphodiesterases (PDEs) are important modulators of inflammation and wound healing. In this capacity, specific targeting of PDEs for the treatment of many diseases, including chronic obstructive pulmonary disease (COPD), has been investigated. Currently, treatment of COPD is suboptimal. PDE4 modulates the inflammatory response of the lung, and inhibition of PDE4 may be a novel, COPD-specific approach toward more effective treatment strategies. This review describes the state of PDE4-inhibitor therapy for use in COPD treatment.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Chronic obstructive pulmonary disease (COPD) is characterized by acute and chronic alterations in the cellular composition structure of the airways and alveoli. Much attention has been focused on the increase in inflammatory cells present both within the airway lumen and within the airway wall. The parenchymal cells of the airway are intimately involved in the recruitment and activation of these inflammatory cells. Conversely, the behaviour of parenchymal cells can be modulated by inflammatory cells. The parenchymal cells can also alter the structural elements present within the airway leading to architecture changes which can impair lung function. Finally, epithelial cells and fibroblasts can directly modify each other's behaviour. The activity of these cells, therefore, undoubtedly can play a variety of roles in the pathophysiologic processes which underlie COPD.