Erdosteine in Chronic Obstructive Pulmonary Disease – Evidence and Current Role

To The Editor, Erdosteine, an oral mucolytic drug, has a potential role management of adult chronic obstructive pulmonary disease (COPD) patients with thick mucus production and difficulty in expectorating. However, the pathophysiology of COPD justifying the use of erdosteine, evidence, and guideline recommendations are evolving. COPD is characterized by dyspnea, cough, and sputum production due to abnormalities of the airways and/or alveoli, causing persistent, progressive airflow obstruction.[1] COPD is associated with increased airway mucus secretion and impaired mucus clearance, leading to excess sputum production. Regular sputum production for 3 or more months, for two consecutive years, is the classical feature of chronic bronchitis. Sputum in COPD patients is usually mucoid, with intermittent flares in quantity and purulence during periods of exacerbation. At times, the sputum may be very viscous, causing difficulty in expectoration and in extreme cases, endobronchial obstruction, and lung collapse. Mucolytics have been used for a long time to improve sputum consistency, facilitate expectoration, and improve airway clearance. Studies have shown that each exacerbation leads to a faster decline in lung functions and increases the risk of mortality in COPD.[2,3] Hence, preventing exacerbations is the key goal of the management of COPD. Chronic sputum production, as well documented in literature, leads to a decline in Forced expiratory volume at second (FEV1) and increases the risk of exacerbations and death. Various mucoactive agents that are used for airway clearance include expectorants, mucolytics, mucoregulatory agents, and mucokinetic agents. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 has provided the algorithm to be used in the management of stable COPD, as well as during exacerbations. Apart from bronchodilators and inhaled corticosteroids (ICS), add-on mucolytic agents such as N-acetylcysteine (NAC) and carbocysteine have also been shown to reduce exacerbations and modestly improve health status. A Delphi study conducted in 2020, involving 53 experts on the treatment of COPD from 12 countries, evaluated the role of carbocysteine, NAC, and erdosteine in COPD management. The experts unanimously agreed that the use of mucolytics reduces exacerbation frequency, reduces the duration of mild-to-moderate exacerbation, increases time to first exacerbation, and symptom-free interval in COPD patients. They also concluded that erdosteine and NAC have antioxidant activity as well, and can improve the efficacy of some classes of antibacterial agents.[4] Erdosteine is a mucolytic agent which reduces the viscosity of the mucus and the purulence of the sputum. It exerts an antioxidant effect on neutrophils and eosinophils because of the scavenging effect of its metabolite. It also affects eicosanoid production in COPD, causing a fall in both leukotrienes (LT) B4 and LTE4 during a 10-day treatment course.[5] Studies have proven its antioxidant effect causing a substantial fall in concentrations of both reactive oxygen species and interleukin-8, besides, leading to a significant fall in levels of 8-isoprostane.[6] It also exerts an antibacterial effect by affecting the integrity of the pilin molecule and prevents the adhesion of bacteria to the airway mucosa.[7] Erdosteine has been shown to improve the amoxicillin concentration in the sputum of patients with chronic bronchitis and improve the anti-adhesive effect of ciprofloxacin and clarithromycin.[8] As compared to other NAC and carbocysteine, erdosteine has been shown to have a better mucolytic and antioxidant effect and had a significant effect on exacerbations in COPD irrespective of treatment with ICS, due to its higher plasma concentration, better protein binding, and faster onset of action.[9] The recent evidence on erdosteine is encouraging. The equalife study studied the efficacy of adding erdosteine 300 mg twice daily versus placebo to the usual COPD treatment for 8 months. Patients on erdosteine therapy had significantly fewer exacerbations and lesser duration of in-hospital stay than placebo.[10] The restore study, a prospective, double-blind, randomized controlled study in patients with COPD studied the efficacy of adding erdosteine 300 mg twice daily versus placebo to the usual COPD treatment for 12 months, in reducing the number of exacerbations. It showed that the addition of erdosteine significantly reduced the number of mild exacerbations by 57% as compared to placebo. It also significantly improved physician’s and patient’s subjective severity scores, and there was a significant reduction in the use of reliever medications.[11] GOLD 2024 also encourages the use of mucolytics such as NAC, carbocysteine, and erdosteine in a select group of patients with COPD. However, erdosteine is to be used as an add-on therapy and not as an alternate to bronchodilators. In addition, prolonged use of erdosteine needs to be evaluated for its long-term efficacy and safety. The use also should be restricted to those subsets of COPD patients who have the phenotype of excessive sputum production and recurrent exacerbations. Due to the potential side effects of headache and dizziness, erdosteine should be used with caution in patients who need to perform tasks such as driving and operating machinery. Furthermore, in view of the lack of proven safety, the use of erdosteine in pregnant or breast-feeding women is not recommended. To conclude, erdosteine as a mucolytic agent could be a beneficial add-on therapy in patients of chronic bronchitis phenotype and COPD with excessive mucus production. However, the use should be individualized. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.