Erdosteine: Antitussive and Anti-inflammatory Effects
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Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine’s ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair β-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to β2 adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on lipoperoxidation (8-isoprostane) proved discriminant between treatments, with antioxidant and anti-inflammatory effects the main determinants of the erdosteine multifactorial properties. In addition, antitussive effects may be regarded as related to its anti-inflammatory properties via the improvement of mucociliary clearance and the reduction of chemokines from epithelial cells. Finally, a sort of “sensitization” of 2-adrenoceptors can also be speculated due to the same mechanisms of action; if confirmed by further controlled studies, this particular property would suggest a novel therapeutic role of erdosteine in COPD.
KeywordsErdosteine Cough Airway inflammation Oxidative stress
In the last decade several studies on animal models pointed at the possible antitussive and anti-inflammatory properties of erdosteine [11, 12] and an indirect anti-inflammatory mechanism of action was suggested . Recently, data from some control-versus-placebo trials documented the antioxidant properties of erdosteine in humans and in current smokers with COPD [13, 14].
Two years ago, a 10-day course with erdosteine at 900 mg/day proved effective in significantly reducing reactive oxygen species (ROS) level in peripheral blood of stable COPD patients who smoke, together with the level of some chemotactic cytokines (IL-6 and IL-8) in their bronchial secretions. Erdosteine induced a substantial drop in the concentration of both ROS and cytokines after a 4-day treatment . The results of this preliminary open study have been confirmed by a recent double-blind, placebo-controlled trial carried out in stable COPD subjects (GOLD class 0–2) treated with erdosteine 600 mg/day. In particular, a significant and substantial reduction in the level of 8-isoprostane (a product of lipid peroxidation) was also documented in the erdosteine group only  since day 7 of treatment.
Finally, it can be speculated that a sort of “resensitization” of β2-adrenoceptors likely occurs according to the above-mentioned mechanisms of action. If confirmed by further controlled studies, this particular property would suggest a novel therapeutic role of erdosteine in long-term treatment of COPD, particularly in smokers.
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