Need for Early Intervention in COPD − A Suitable Time for Mucolytic Treatment
Chronic Obstructive Pulmonary Disease (COPD) ranks third among the leading causes of morbidity and mortality worldwide, with more than 210 million people expected to be affected by 2030. While common, it is preventable and treatable. The mucolytic erdosteine has proven to be an effective helper in COPD therapy.
The above information was among the topics discussed at this year's Hradec Pneumological Days (HPD 2022), where Professor Clive Page from King’s College in London kicked off his lecture. He followed with a reminder of the pathogenesis of COPD, noting that the bronchial obstruction characteristic of this disease results from the presence of emphysema along with chronic bronchitis. Mucus hypersecretion and oxidative stress are common reasons for treating COPD with mucolytics/antioxidants. It is also known that exacerbations and comorbidities are the main factors driving the progression of this disease.
Delphi Project
The administration of mucoactive drugs in COPD has been investigated in numerous studies. Researchers questioned whether all mucoactive substances offer the same effects in COPD, in terms of therapeutic effect or safety profile. The speaker highlighted the Delphi project (Papi et al., 2020), in which the role of mucolytics in COPD was evaluated by an international panel of 53 COPD experts from 12 countries (including 5 experts from the Czech Republic). The panel analyzed the results of erdosteine, carbocisteine, and N-acetylcysteine (NAC) in the following parameters: synergy with antibiotics (ATB), frequency of exacerbations, duration and prevention of exacerbations, time to the first exacerbation, symptom reduction, symptom-free period, risk of hospitalization, and safety profile.
The findings from the Delphi project support the broader use of mucolytics as an adjunctive therapy for COPD. However, the level of consensus varied for each evaluated mucolytic. Erdosteine received the most favorable opinion, achieving the highest consensus on its selection as the mucolytic of choice for patients with COPD.
RESTORE Study – Real-World Data
The impact of erdosteine on the rate and duration of COPD exacerbations in the real world was assessed in the randomized, double-blind, placebo-controlled RESTORE study. The study involved 528 COPD patients treated at 47 centers in 10 EU member countries. Participants received either 300 mg of erdosteine (600 mg daily) or placebo twice daily for 12 months, continuing their baseline COPD treatment.
The authors concluded that erdosteine reduces the rate and duration of exacerbations in COPD patients, improves their health status, is not affected by the use of inhaled corticosteroids (ICS), and is well tolerated.
A post hoc analysis of the RESTORE study showed that in patients with moderate COPD, the mean exacerbation rate per patient per year with erdosteine was nearly half that of those receiving placebo (−47.0%; 0.27 vs. 0.51). The annual incidence of mild exacerbations per patient was reduced even more with erdosteine compared to placebo (−58.3%). The mean duration of the exacerbation-free period per year was 51 days longer in the erdosteine arm compared to the placebo arm. The safety profiles of erdosteine and placebo were similar.
Importance of Early Intervention Including Mucolytic
Early intervention is crucial for achieving the best clinical outcomes in COPD treatment. Early initiation of appropriate pharmacotherapy can benefit the patient in terms of disease progression, overall clinical outcomes, amelioration of lung function deterioration, and improvement of health status. This is particularly critical for patients in the early stages of COPD.
The new recommended guidelines from the Global Initiative for COPD (GOLD) officially re-confirmed the superiority of erdosteine compared to other mucolytics. “In COPD patients not receiving ICS, regular treatment with mucolytics such as carbocisteine and NAC may reduce exacerbations and slightly improve health status. In contrast, erdosteine has been shown to have a significant effect on (mild) exacerbations regardless of concurrent ICS treatment,” according to this year's GOLD report. ICS is used by 42–86% of COPD patients. Therefore, according to GOLD, erdosteine is the mucolytic of choice for COPD as it is effective in all patients with this diagnosis irrespective of concurrent ICS use.
Synergy of Erdosteine and Antibiotics
Bacterial infections are a significant burden in COPD, as 50–70% of COPD exacerbations are caused by bacteria. The main issue is their ability to form biofilms, a significant reason for antibiotic failure. Bacterial resistance to antibiotics is a major global problem and, as predicted by the European Medicines Agency (EMA), will remain so for decades to come.
Concerning interactions between antibiotics and erdosteine, a very favorable effect has been demonstrated. When these medications are administered together, erdosteine enhances antibiotic activity and prolongs antibiotic anti-adhesion effects on bacteria (Pani et al., 2022), thereby increasing treatment efficacy. This significantly differentiates it from NAC, which can even inactivate antibiotics and is therefore not recommended for use with some antibiotic groups (see SPC). On the contrary, erdosteine as an adjunctive COPD therapy is considered effective and a means to reduce antibiotic consumption. It has also been evaluated in combination with vancomycin in cases of MRSA (methicillin-resistant S. aureus) biofilm formation.
Erdosteine also reduces the adhesive ability of both gram-positive and gram-negative bacteria to the respiratory epithelium. This in vitro proven effect may limit bacterial colonization and reduce the risk of bacterial superinfection. Additionally, it increases the concentration of amoxicillin in bronchial secretions, resulting in a faster onset of antibiotic efficacy when administered concurrently with amoxicillin compared to amoxicillin monotherapy.
Conclusion
To avoid COPD progression and mitigate lung function deterioration, early treatment initiation is desirable. Erdosteine reduces the rate and duration of exacerbations and prolongs exacerbation-free periods, particularly in early-stage disease patients. Studies indicate it is the only mucolytic effective in COPD patients irrespective of concurrent use of inhaled corticosteroids, enhances antibiotic activity, and shares a safety profile comparable to placebo. In the strategy of
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