Pharmacology and Clinical Efficacy of Erdosteine in Chronic Obstructive Pulmonary Disease

Maurizio Moretti


Expert Rev Resp Med. 2007;1(3):307-316. 

In This Article

Abstract and Introduction

Erdosteine is a multimechanism, mucolytic agent that decreases the sputum viscoelastic properties and bacterial adhesion to the cell membrane, endowed with bronchial anti-inflammatory activity and a scavenging effect on free oxidant radicals. Erdosteine is a prodrug and metabolite I is the active metabolite of erdosteine owing to its free thiol group. In acute infective exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (COPD), adding erdosteine to standard treatment significantly modified the outcome by improving the symptoms and reducing the length of disease. Furthermore, erdosteine has shown a synergism with antibiotic therapy. In stable COPD patients, long-term treatment with erdosteine had a protective effect against exacerbations by reducing the rate of exacerbations and hospitalizations in the study period. A total of 8 months of treatment with erdosteine significantly improved the patients' health status and preserved lung function. Erdosteine has a scavenging effect on free oxidant radicals by a direct and indirect antioxidative effect and the final result is a protective effect against tissue damage, as demonstrated in animal studies. In view of the persuasive evidence that oxidative stress is important in the pathophysiology of COPD, erdosteine appears to be a logical approach to therapy.

At least half of smokers will develop chronic bronchitis (CB), cough and sputum without lung-function impairment, and up to 15% will develop chronic obstructive pulmonary disease (COPD) symptoms plus lung-function impairment. COPD is a major and increasing health problem, which is predicted to become the third most common cause of death and the fifth most common cause of disability in the world by 2020.[1]

COPD has a very complex pathogenesis, in which the typically occurring airflow limitation is only the final consequence of a cascade of events that start much earlier than the appearance of the clinical symptoms of the disease.

Actually, COPD is considered as an inflammatory disease caused mainly by oxidative stress.[2] Oxidants encompass reactive oxidant species (ROS; e.g., hydrogen peroxide, superoxide anion and hydroxyl radical), reactive nitrogen species and various others. ROS are at the basis of the process of COPD development; ROS can derive from exogenous (mainly cigarette smoke and air pollution) or endogenous sources (activation of neutrophils, epithelial cells and other phagocitic cells due to bacterial or viral infections or cigarette smoke). Oxidants are associated with direct toxicity to key lung structures and/or as mediators in a variety of processes that may promote the development of COPD. For example, oxidants increase mucus production and mucus viscoelastic properties, impairing mucociliary clearance and provoking airway bacterial colonization, chronic cough and bronchial obstruction. Oxidants activate proteases, such as collagenases, inactivate antiproteases, such as α1-antitrypsin, and shift the protease–antiprotease balance towards increased proteolysis;[3] the consequence is the progressive destruction of the structures, which leads to emphysema, commonly present in the advanced stages of COPD.[4,5] The anatomical and functional damages described briefly explain the clinical picture of COPD: mucus hypersecretion, cough and dyspnea; moreover, it is clear why the airflow limitation that is the typical feature of COPD is only partially reversible. There is also increasing evidence that oxidative stress is involved in the pathogenesis of systemic phenomena, such as skeletal muscle dysfunction and, perhaps, even the increased cardiovascular risk of mortality that results from COPD.[6–7]

People with CB or COPD may experience recurrent exacerbations with worsening symptoms or greater volume or purulence of sputum. These exacerbations contribute to morbidity and poorer health, as well as to increased healthcare costs. Although these exacerbations can be treated acutely with antibiotics or steroids, it would be useful to have other treatments that reduced the frequency and duration of acute exacerbations. The management of individual patients with COPD should be guided by the symptoms and disability that they experience. Management of COPD usually involves preventive measures, such as smoking cessation, medical treatments and pulmonary rehabilitation. Medical treatments include bronchodilators, corticosteroids, antibiotics and mucolytic agents. Mucolytics are administered to reduce sputum viscoelastic properties and improve sputum production.

In the acute setting, such as exacerbation of CB or COPD, addition of mucolytic agents to standard treatment improves the symptoms and reduces the time of disease. In clinically stable COPD, treatment with mucolytics is associated with a reduction in acute exacerbations and length of illness. The Cochrane systematic review provided a helpful analysis of relevant randomized, controlled trials of different mucolytic agents.[8] The analysis concluded that these drugs, taken long term, could be most useful in patients who have repeated, prolonged or severe exacerbations of COPD. Hence, in some European and extra-European countries, mucolytics are prescribed widely since they appear to reduce the frequency of exacerbations and/or reduce symptoms in patients with CB or COPD. Some of these drugs, such as thiol agents, also have antioxidative effects that may contribute to their clinical effects.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.