Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation caused by airway and/or alveolar abnormalities (1). Over the period from 1970 to 2002, the mortality rate attributed to COPD doubled, highlighting the significance of this condition (2). It is recognized as a major cause of morbidity and mortality globally, leading to a substantial social and economic burden (3, 4). In light of these concerns, we initiated this trial. According to the World Health Organization (WHO), COPD is currently the third leading cause of death, accounting for approximately 6% of total deaths in 2019 (5). In China alone, it was estimated that around 99.9 million individuals were affected by COPD (6). The burden of morbidity and mortality associated with COPD remains a pressing issue.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) (1) emphasizes that the main treatment goals for stable COPD are the reduction of symptoms and the prevention of future exacerbations. Tiotropium bromide, a maintenance therapy for stable COPD (7), has demonstrated significant benefits in terms of reducing symptoms such as dyspnea, slowing lung function decline, decreasing exacerbation rates, and improving quality of life (8). Furthermore, an increasing body of evidence supports the unique advantages of traditional Chinese medicine (TCM) in clinical practice. The combination of TCM with conventional Western medicine has shown significant differences in acute exacerbation frequency, duration, symptoms, 6-min walking distance (6MWT), and dyspnea scale (9). A clinical trial has also indicated that Jinshui Liujun decoction has significant clinical efficacy in the treatment of severe and extremely severe COPD in the elderly. It can effectively alleviate clinical symptoms, reduce the number of acute exacerbations, alleviate inflammatory reactions, and improve quality of life (10). A meta-analysis implied that the CAT score, mMRC and average hospitalization time were also reduced significantly by Shengmai injection plus western medicine (11).

Moreover, experimental studies exploring the underlying pathological mechanisms have revealed the potential benefits of TCM in COPD. For instance, One network pharmacology indicated that Jinshui Liujun decoction can treat COPD through the synergy of multiple ingredients, multiple targets and multiple pathways (12). However, limited multi-center randomized controlled trials (RCTs) have been conducted to validate the efficacy of TCM in the treatment of stable COPD. Therefore, we have designed an RCT to evaluate the effectiveness of comprehensive therapy based on a specific TCM pattern in stable COPD patients. Traditional Chinese herbs used in this trial, as a combination of Jinshui Liujun decoction and Shengmai decoction, consist of Danggui [Dry root of Angelica sinensis (Oliv.) Diels.], Shudi (Dried root of Rehmannia glutinosa Libosch.), Chenpi (Dried mature pericarp of Citrus reticulata Blanco.), Jiangbanxia [Underground tubers of pinellia ternate (Thunb.) Breit processed with ginger and alum.], Fuling [Sclerotium of Poria cocos (Schw.) Wolf.], Zhigancao (Dry roots and rhizomes of Glycyrrhiza uralensis Fisch, Glycyrrhiza inflata Bat, Glycyrrhiza qlabra L.), Taizishen [Dry root tubers of Pseudostellaria heterophylla (Miq.) Pax ex Pax et Hoffm.], Tiandong [root tuber of Asparagus cochinchinensis (Lour.) Merr.], Maidong (Fleshy root of Ophiopogon japonicus Ker-Gawl.), Wuweizi (Matured fruits of Schisandra chinensis Baill.), Huangqi [Dried root of Astraqalus membranaceus Bge. Var. mongholicus (Bge.) Hsiao, Astraqalus membranaceus (Fisch.) Bge.]

Shortness of breath, chronic cough, and sputum are considered characteristic symptoms of COPD. Our research findings indicate that the combined use of TCM and western medicine reduced clinical symptoms, particularly in sputum, compared to the control group (p < 0.05). In the sixth month of the trial, the TCM granule treatment demonstrated superiority in terms of the total effective rate (p < 0.05), highlighting its potential in improving clinical symptoms.

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2020) (1), a COPD exacerbation is defined as an acute worsening of respiratory symptoms that requires additional therapy, such as hospitalization. Our findings revealed that the combined use of TCM and western medicine reduced the frequency and duration of hospitalization compared to baseline. COPD exacerbations are complex events, often triggered by respiratory viral or bacterial infections (17). It has been reported that COPD patients with positive cultures for P. aeruginosa in the airways have an increased risk of exacerbations (18). This underscores the importance of infection prevention in reducing COPD exacerbations. Some studies have suggested the potential of TCM in preventing viral infections (19, 20). Unfortunately, our findings did not show a significant difference in exacerbation rates between the trial group and control group. This may be attributed to limitations in follow-up time and sample size. Additionally, we acknowledge the complexity of evaluating exacerbations, as non-infectious factors such as age, gender, and comorbidities can also contribute. A novel risk score called BODEx (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) has been proposed to assess COPD exacerbations in relation to comorbidities (21). Incorporating comprehensive factors, including clinical parameters, comorbidities, occupation, and economic status, in future questionnaires may enhance our sensitivity in evaluating the effects of TCM on COPD.

Patients’ quality of life was assessed using the CAT questionnaire. Our research findings indicate that the combined use of TCM and western medicine led to a reduction in CAT scores, although no significant difference was observed compared to the control group. This implies that TCM did not demonstrate superiority over placebo, which may be due to the insufficient sample size. We observed a significant reduction in sputum, one of the items in the CAT, with the use of TCM. However, we did not observe a similar improvement in shortness of breath and cough, which might have contributed to the lack of overall superiority in the CAT scores. In the future, adjustments can be made to enhance the efficacy of TCM in addressing shortness of breath and cough.

Exercise tolerance was assessed using the 6MWT and mMRC. Although both measures showed improvement after treatment, the trial group did not exhibit superiority compared to the control group. It is worth noting that the 6MWT is a cost-effective and well-tolerated test, but it is highly sensitive to variations in methodology and environmental factors. On the other hand, the mMRC scale has a short completion time but only assesses breathlessness (22). Moreover, exercise tolerance is not easily modifiable, and the treatment period may have been too short. These observations indicate that a one-year observation period may not be sufficient to detect significant changes in exercise tolerance.

Lung function parameters, particularly FVC (%), FEV1 (%), and FEV1/FVC, are vital for evaluating the effectiveness of TCM granules. At baseline, significant differences were observed in FVC and FEV1 (p < 0.05). The Normative Aging Study has reported that FEV1 is more strongly associated with mortality than FVC in the general population (23). Additionally, another study highlighted that FEV1 is a stronger predictor of all-cause mortality than FVC in moderate COPD patients with an elevated cardiovascular risk (24). Based on our research, during month 6 and month 12, both FEV1 (p < 0.001, p = 0.003) and FEV1% (p < 0.001, p = 0.029) significantly improved in the trial group compared to baseline. Furthermore, during month 6 and month 12, the D-value of FEV1 in the trial group exhibited a significant difference compared to the control group (p = 0.046, p = 0.013), suggesting that the combined use of TCM and western medicine achieved a sustained superior effect compared to monotherapy with western medicine.

Additionally, the D-value of FVC% also exhibited a significant difference compared to the control group, revealing the superiority of the co-application of TCM and western medicine. Previous research has indicated a strong positive correlation between peak oxygen uptake (VO2peak) (% pred.) and FEV1 (% pred.) (25). This suggests that FEV1% may potentially reflect a patient’s maximum aerobic capacity. During month 6, both FVC and FEV1% in the trial group showed a significant difference compared to baseline, suggesting that the co-application of TCM and western medicine may increase patients’ maximum aerobic capacity after treatment. However, further investigation is needed to verify this relationship in the future. Furthermore, during month 12, the control group exhibited an obvious decline in FEV1/FVC compared to baseline, while the trial group showed no significant difference in comparison to baseline. This may imply that the combination of TCM and western medicine could suppress the deterioration of FEV1/FVC. Overall, TCM granules, when used in combination with western medicine, demonstrate potential in improving lung function.

Regarding adverse events, no significant differences were observed between the trial group and control group, indicating the safety of applying TCM clinically.

There are several limitations to our trial. The final number of included cases was smaller than the estimated sample size based on efficiency in the previous stage, which may introduce bias into our research results. However, considering the superiority of the total effective rate in the trial group during month 6, our research results are reliable and support the research hypothesis. Second, this trial was concluded in 2015, and the data may be considered “out-of-date.” However, we obtained similar conclusions to a meta-analysis published in 2021, such as alleviating clinical symptoms, reducing exacerbation frequency, improving quality of life, and demonstrating clinical efficacy (26). Thus, our trial still provides valuable evidence to verify the effectiveness of TCM in clinical practice.

In this study, we evaluated the efficacy of TCM in various aspects, including clinical symptoms, lung function, hospitalization, quality of life, and safety. The results demonstrate that the combination of western medicine and TCM is superior to western medicine monotherapy in stable COPD patients, particularly in terms of sputum symptoms, D-value of FVC%, and FEV1. This indicates the potential for further exploration of TCM in the treatment of COPD.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, with the approval identifier 2012-K-001-02. Trial registration number: ChiCTR-TRC-13003531, registered on August 29, 2013. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

RC: Writing – original draft, Data curation. KN: Writing – original draft, Visualization. CJ: Writing – review & editing, Methodology. ZL: Writing – review & editing, Investigation. YY: Writing – review & editing, Investigation. GL: Writing – review & editing, Investigation. JY: Writing – review & editing, Data curation. ZW: Writing – review & editing, Funding acquisition, Conceptualization.