Abstract
Objective:
To observe the clinical efficacy of Chinese herbal medicine combined with Liuzijue exercise on the physiological symptoms and quality of life (QoL) in postoperative patients with early-stage lung cancer.
Methods:
One hundred and eighty-three lung cancer patients who underwent video-assisted thoracoscopic surgery (VATS) were categorize into either a traditional Chinese medicine treatment group (CM) or a control group (non-traditional Chinese medicine treatment, NC), among whom 73 underwent Chinese herbal medicine and Liuzijue therapy, while 110 underwent no comprehensive treatment with traditional Chinese medicine. The propensity score matching (PSM) method with a 1:2 ratio was used to balance the baseline characteristics and evaluate the efficacy of CM in improving postoperative symptoms and QoL.
Results:
Cough, dyspnea, chest pain, and fatigue were the most common clinical symptoms after VATS. Except for chest pain, they were all correlated with the scope of operation (P < .05). After PSM, 165 patients were identified in the matched cohort, and the covariates of gender, age, operative site, and scope of operation were balanced between the 2 groups (P > .05). In the domain of global health status, the improvement in QoL in CM was greater than that in NC (6.06 ± 15.83 vs −1.06 ± 14.68, P = .005). In terms of symptoms, improvements in cough (1.69 ± 3.15 vs 0.38 ± 2.63, P = .006), dyspnea during climbing stairs (−10.30 ± 16.82 vs −1.82 ± 17.97, P = .004), and pain (−0.76 ± 1.32 vs −0.08 ± 1.31, P = .002) in CM were better than in NC.
Conclusion:
Comprehensive treatment with traditional Chinese medicine (TCM) can provide therapeutic benefits in physiological rehabilitation after VATS for cancer.
Keywords
Introduction
Lung cancer continues to be the leading cause of cancer-related deaths in 2023. 1 Radical operation remains the most effective treatment for early-stage non-small cell lung cancer (NSCLC), and VATS has been firmly established as the preferred operative approach for curative resection.2,3 Compared to the traditional thoracotomy approach for lobectomy, VATS offers numerous advantages, including a shorter hospital stay, faster recovery, fewer perioperative complications, and improved long-term survival. 4
Khullar et al 5 found that 1 month after the operation, lung cancer patients experienced a significant increase in pain, fatigue, and sleep disorders, resulting in a decline in their physical functions. Over 70% of postoperative patients reported symptoms such as fatigue, dyspnea, cough, and expectoration during the first month. Although these symptoms tended to subside between the second and fourth months, >60% of the patients still experienced them. 6
Pulmonary rehabilitation programs can enhance respiratory muscle strength and aerobic capacity, thereby alleviating symptoms. 7 However, despite patients’ willingness to participate in exercise after lung cancer surgery, participation remains insufficient due to misconceptions. 8
Chinese herbal medicine, with its multi-component and multi-target characteristics and strong safety profile, is guided by a holistic concept and syndrome differentiation and demonstrates remarkable clinical effects in improving symptoms. 9 Traditional Chinese exercises, including tai chi, Liuzijue, Wuqinxi, and Yijinjing, have a positive impact on patients with lung diseases. 10 Among them, Liuzijue is a type of traditional recreational exercise known as “qigong” that promotes both physical and mental health. 11 Liuzijue is distinguished by its unique set of special breathing and pronunciation techniques, which involve exhaling with the sounds “Xu,” “He,” “Hu,” “Si,” “Chui,” and “Xi.” These techniques are unique in balancing the energy and functions of the internal organs, particularly the lungs. The movements are simple and soothing, making it easier for postoperative patients to embrace them.
As our previous study demonstrated, for patients with stage Ia to Ib NSCLC who underwent VATS, the combination of Chinese herbal medicine and lung rehabilitation training (such as cycling or jogging) was found to alleviate cough and fatigue symptoms more effectively than a placebo combined with rehabilitation education. 12 This study further examined the clinical efficacy of combining Chinese herbal medicine with Liuzijue exercise in terms of physiological symptoms and quality of life (QoL) among postoperative patients with early-stage lung cancer. Here, we present the findings on symptoms and QoL outcomes.
Methods
Study Population
The inclusion criteria were as follows: (1) NSCLC patients 4 to 6 weeks after VATS with stage Ia to Ib; (2) no adjuvant Western medicine treatment, such as chemotherapy, radiotherapy, or targeted therapy after surgery; (3) has a performance status (PS) score of 0 to 2 points; and (4) signed informed consent. The exclusion criteria were as follows : (1) more than 6 weeks after VATS; (2) with a mental illness or has difficulty completing the QoL scale; and (3) allergic to the study drug or is undergoing other clinical trials.
Trial Design and Treatment
The trial was based on the principles of contemporaneous, parallel and control, and used the method of prospective PSM. The patients were divided into CM and NC groups according to their willingness to receive the comprehensive treatment with TCM. The clinical trial was retrospectively registered: ChiCTR2100044843. This project was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (No: 2020-038). All participants signed the informed consent before taking part in this study and any intervention.
All enrolled patients received symptomatic and supportive Western medicine treatment following the Chinese Guidelines for Perioperative Airway Management in Thoracic Surgery (2020 edition). NC patients were treated with rehabilitation education and allowed to do their own breathing training at home at least once a day for 30 minutes each time. CM patients were treated with the comprehensive TCM treatment, including oral Chinese medicine and improved Liuzijue exercise. Both groups were treated and observed for 8 weeks after enrollment.
CM Prescription and Improved Liuzijue Exercise
Symptoms after lung cancer surgery are divided into 3 basic syndromes: wind invading the lung, stagnation of Qi and accumulation of phlegm, or deficiency of the lung and spleen (Table 1). One experienced TCM physician with a senior professional title was assigned to syndrome differentiation. Details of the specific medication and dosage of the prescription are shown in Supplemental Table S1. All the oral Chinese medicine decoctions came from the TCM pharmacy of Yueyang Hospital. The decoction process strictly followed the Good Manufacturing Practice (GMP) system. The herbs were decocted with water and divided into 2 bags of 150 mL of liquid. Patients took it twice a day, one bag each time, for 8 consecutive weeks.
TCM Syndrome Differentiation and CM Prescription*.
Based on the Chinese medicine industry standard of the People’s Republic of China “Traditional Chinese Medicine Syndrome Diagnosis and Efficacy Standards” (ZY/T001.1-94).
Improved Liuzijue exercise included warm-up, breathing training, qigong, and relaxation. The specific training method is shown in Supplemental Table S2 and Figure S1. Professional doctors provided guidance on improved Liuzijue exercise and distributed teaching videos to ensure that each patient could master and independently complete them. Patients exercised at least once a day for 30 minutes each time for 8 consecutive weeks, and they were required to record their exercise duration, location, and completeness. Daily exercise was supervised separately by 3 follow-up physicians.
Outcomes
The primary endpoint of this trial was QoL, which was assessed using the QLQ-C30 and QLQ-LC13 scales 13 developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess QoL. The secondary endpoint was physiological symptom assessment, such as using the Leicester cough quality of life questionnaire (LCQ) 14 to evaluate cough, Q3-Q5 in QLQ-LC13 to evaluate dyspnea, and the numerical rating scale (NRS)15,16 to evaluate pain. Following the Common Terminology Criteria for Adverse Events (CTCAE) 5.0, routine blood examinations and serum biochemical tests were used to determine the safety of test administration.
Statistical Analysis
According to the previous research results of this trail, based on the validity hypothesis, QoL improved by 40% in CM and 22% in NC. The ratio of cases between CM and NC was 1:1. Using PASS 11.0 software with α = .05 and 1-β = .80, the sample size was calculated to be 113 cases in each group. However, due to the COVID-19 epidemic, we ultimately enrolled 73 patients in CM and 110 patients in NC.
This was a non-randomized intervention study. Gender, age, and the scope and site of operation were used as variables for balancing and matching groups for PSM. PSM was performed with Stata/SE. For the comparability of the 2 cohorts and to reduce censoring, CM and NC were nearest-neighbor matched at a ratio of 1:2 to obtain the final cohort for analysis.
SPSS 26.0 software was used for statistical processing. Normally distributed measurement data were analyzed using a t-test, while measurement data that did not conform to the normal distribution were analyzed using the Wilcoxon rank-sum test. Enumeration data were analyzed using a chi-squared test. Correlation analysis was done using Spearman’s correlation coefficient, and multivariate analysis was done using linear regression or logistic regression. P < .05 was considered statistically significant.
Results
Patient Disposition and Characteristics
From July 2020 to January 2022, there were 203 patients screened at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine and Shanghai Pulmonary Hospital. Twenty cases failed the screening, and 183 patients who met the inclusion criteria were subjected to PSM. Ultimately, 55 and 110 patients were included in CM and NC, respectively (Figure 1).

Study flow diagram.
Before PSM, the distributions of patients in CM and NC were different, and the baseline was unbalanced. After PSM, there was no significant difference between the 2 groups in terms of gender, age, operative site, and scope of operation (P > .05) (Table 2). It was found that the matching effect was good after testing the matching common support domain (Supplemental Figure S2).
Baseline demographic and clinical characteristics before and after PSM.
Characteristics of Physiological Changes After VATS
The EORTC QLQ-C30 and QLQ-LC13 scales were used to analyze the total QoL of 183 patients before PSM. Before treatment, the Global Health Status score of patients was 70.81 ± 19.08. In terms of function, the scores from low to high are role, social, physical, emotional, and cognitive, and the differences in various domains are statistically significant (Figure 2A, P < .01). In terms of symptoms, fatigue, dyspnea, and insomnia scored higher than others(Figure 2B, P < .01). For the lung cancer module, cough, dyspnea, and chest pain scored higher than others (Figure 2C, P < .01).

(A-C) EORTC QLQ-C30 and QLQ-LC13 scores before PSM. Univariate ANOVA analysis was performed on the 3 parts of data in (A-C) P < .01. (D) Heat Map. Spearman’s rho was performed. *Correlation is significant at the .05 level (2-tailed). **Correlation is significant at the .01 level (2-tailed).
The most obvious postoperative symptoms included fatigue, dyspnea, cough, and chest pain, which were selected to explore the correlation between symptoms and gender, age (<65 years old or ≥ 65 years old), and surgical methods. Spearman correlation analysis showed that fatigue was correlated with gender, age, and scope of operation, dyspnea was correlated with age and scope of operation, and cough was correlated with scope of operation. Then, statistically significant indicators were analyzed by linear regression analysis, which showed that gender and age were independent influencing factors of fatigue, and scope of operation was an independent influencing factor of dyspnea and cough (Figure 2D).
Comprehensive Treatment With TCM in Physiological Rehabilitation
The influence of comprehensive treatment with TCM on QoL
The scores before and after treatment (8 weeks) are shown in Supplemental Table S3. The difference value was obtained by subtracting the score before treatment from that after treatment. In the domains of global health status and dyspnea, the improvement of QoL in CM was greater than that in NC (Figure 3A-C, P < .01). An analysis of the proportion of patients whose QoL scores improved, remained stable, or worsened in the 2 groups revealed that in domains such as global health status, cough, dyspnea, and pain, the curative effect of CM was superior to that of NC. (Figure 3D-F).

(A-C) The mean change from baseline of QLQ-C30 and QLQ-LC13 scores. (A) EORTC QLQ-C30 function domains and global health status; (B) EORTC QLQ-C30 symptom domains; (C) EORTC QLQ-LC13 scales. All items were consistent with normality, and independent sample T test was used. (D-F) Proportion of patients with improved, stable and worsened quality of life. * P < .05,** P < .01.
The influence of comprehensive treatment with TCM on common symptoms

(A) The LCQ domain scores to assess cough. (B) The mean change from baseline of LCQ. (C) The Q3-Q5 in QLQ-LC13 scores to assess dyspnea. (D) The mean change from baseline of Q3-Q5. All items were consistent with normality, and independent sample T test was used.* P < .05,** P < .01 . (E) The NRS pain intensity.
Improvements in common symptoms such as cough, dyspnea, and pain in CM were better than in NC.
Safety Assessment of Comprehensive Treatment With TCM
Before PSM, 73 patients received comprehensive treatment with TCM. The safety of comprehensive treatment was evaluated through hematology examinations of these 73 patients. Abnormal hematological indicators were observed both before and after treatment. Specifically, before treatment, 4.69% of patients exhibited abnormal white blood cell (WBC) counts, with a maximum of 18.28 × 109/L; 10.94% had abnormal neutrophils (NEUT) levels, with a maximum of 14.73 × 109/L; 12.50% had abnormal hemoglobin (HGB) levels, ranging from a minimum of 91 g/L to a maximum of 151 g/L; 15.62% showed abnormal alanine amino transferase (ALT) levels, ranging from a minimum of 6 U/L to a maximum of 124 U/L; 12.50% had abnormal aspartate amino transferase (AST) levels, ranging from a minimum of 11 U/L to a maximum of 60 U/L; and 3.12% had abnormal creatinine (Cr), with a maximum of 98 µmol/L. Following treatment, the values were closer to normal.
According to the evaluation using CTCAE 5.0, there were some adverse events (AEs) both before and after treatment, all of which were Grades 1 to 2 (Table 3). During the entire treatment process, there were no Grade 3-5 AEs, no severe adverse events (SAEs), no AEs related to the medication, no participants who withdrew from the study or stopped the trial, and no deaths that occurred due to AEs.
Summary of adverse events (Grade 1-2) [n (%)].
Discussion
This study revealed that the most troublesome symptoms experienced by patients with lung cancer after surgery were fatigue, dyspnea, cough, and chest pain, which seriously impact the QoL of these patients. Following VATS, lung tidal volume decreases, while the residual volume increases due to chest wall damage, respiratory muscle ruptures, and nerve reflex inhibition. 17 Ventilation function decreases, resulting in a subsequent reduction in maximum oxygen consumption and a significant decline in exercise tolerance. 18 Therefore, postoperative lung cancer patients often experience chest tightness, dyspnea, and fatigue. The cause of postoperative cough is related to the depth and scope of lymph node dissection. During this process, the main trachea is affected to some extent. After the cleaning, the lymph node fossa remains empty and lacks support around the main trachea. The receptors are exposed, causing irritation and cough. 19 In addition, anatomical and physiological changes resulting from pulmonary resection are other crucial factors, and alterations in airflow dynamics or airway sensitivity during respiration can also trigger coughing. 20 Chronic persistent pain after surgery represents a significant clinical challenge in 25% to 60% of patients, with neuropathic components stemming from injury or irritation of the intercostal nerve. This pain is primarily described as aching, tender, numb, and, to a lesser extent, burning. 21 Although VATS reduces acute postoperative pain by minimizing surgical incision, mitigating intercostal nerve damage, and preserving the integrity of the chest wall, chronic persistent pain following surgery still persists.
Previous studies have confirmed that the most prominent postoperative symptoms can be traced to specific causes, emphasizing the significance of physiological rehabilitation after surgery. In 2013, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) proposed the concept of “pulmonary rehabilitation.” 22 In addition to taking antispasmodic cough and analgesic drugs, effective breathing, active coughing, and other lung function training can help smooth the discharge of sputum, effusion, and gas; reduce the pain caused by respiratory dilation exercise; and greatly improve lung ventilation.23,24 Surgeons encourage patients to climb stairs, blow balloons, or use respiratory trainers early after surgery to improve lung function. They also recommended performing incision-site stretching exercises to prevent chronic pain resulting from pleural adhesions, thereby promoting postoperative recovery.
However, we found that patients do not receive timely pulmonary rehabilitation training due to various issues. After surgery, patients are prone to fatigue, and even slight activities can lead to dyspnea. Consequently, they are typically more inclined to rest in bed or in a sitting position, neglecting lung rehabilitation training. Furthermore, patients tend to resist local stretching exercises due to incision pain or fear of incision rupture. In this study, regardless of whether the patients were in CM or NC, we conducted close follow-ups for each patient. This approach helped dispel any misunderstandings, encouraged patients to adhere to postoperative pulmonary rehabilitation training, and contributed to the physiological recovery of patients to a certain extent.
According to the TCM theory, Qi (vital energy) is regarded as the driving force behind biological activities in the human body, encompassing both nutrient substances and organ functions. 25 Qi deficiency, Qi depression, Qi stagnation, Qi inversion, and other states affect the normal physiological functions of the patient’s body. A Sangju decoction can inhibit wind, diffuse lung Qi, and suppress cough, 26 which is suitable for patients with Qi inversion based on syndrome differentiation. A Banxia Houpo decoction can improve the cough reflex of patients 27 and is suitable for patients with Qi stagnation. A Shengxian decoction has been reported to improve energy metabolism and have anti-cancer activity,28,29 which is suitable for patients with Qi deficiency. Chinese herbal medicine treatment based on syndrome differentiation makes postoperative physiological rehabilitation more targeted. Taking the Banxia Houpo decoction as an example, the Pinellia Tuber in the prescription can regulate Qi and dispel phlegm and is a Chinese herbal medicine that is used to treat cough, insomnia, nausea, inflammation, and epilepsy. 30 The Perilla Leaf has been widely used to treat various diseases, such as colds, headaches, and cough, and Perilla leaf ethanolic extract has been proven to suppress the expression and production of TNF-α/IFN-γ-stimulated proinflammatory chemokines by blocking NF-κB, STAT-1, and MAPK activation. 31 The Poria cocos polysaccharide (PCP) is the major active constituent of Poria; PCP and its derivatives exhibit diverse biological functions, such as antitumor, antioxidant, anti-inflammatory, immune-regulatory, and hepatoprotective functions. 32 Research has confirmed that PCP may exhibit immunomodulatory activity through TLR4/TRAF6/NF-κB signaling both in vitro and in vivo. 33 At the same time, Liuzijue exercise can regulate and control the rise and fall of Qi inside the body and related inhalation and exhalation. The exercises are based on the pronunciation of 6 sounds during exhalation, accompanied by typical and simple movements. Safety and efficiency are the strengths of Liuzijue. First, the movements are simple and easy to perform, the exercise load is not too heavy, and the amount and duration of exercise is easy to control, so it is easier to be accepted by patients who neglect or resist postoperative exercise. Second, Liuzijue could improve QoL, exercise tolerance, and lung function, 34 which can improve symptoms such as fatigue and dyspnea. Compared with aerobic training, Liuzijue exercise can improve immune homeostasis. 35
The results showed that Chinese herbal medicine combined with improved Liuzijue exercise had a good curative effect on physiological rehabilitation, and their safety was also confirmed. No adverse events related to the medication occurred during the whole treatment process. The expression levels of inflammatory markers, such as WBC and NEUT, were correlated with bacterial infection. 36 Serum ALT and AST levels increased when hepatocytes were damaged. 37 The damage was typically caused when the intraoperative administration of fat-soluble and non-depolarized anesthetic drugs surpasses the liver metabolic capacity. This abnormal liver function is most obvious 1 to 3 days after the operation and returns to normal after 7 to 10 days. 38 Cr is a product of muscle metabolism. During operation, patients maintain the same position for a long time, and muscle injury easily occurs via muscle pulling and lung tissue excision, which may result in physiologic Cr increase. 39
However, due to the limitations of PSM research, only hematological indicators of patients with TCM comprehensive intervention were obtained, and outliers were not excluded during inclusion. Since it was observed that the patients had a tendency to heal themselves in terms of liver function, we did not use liver-protecting drugs to intervene. During the investigation and analysis of these patients, abnormal ultra-high indexes showed a downward trend, and most returned to normal. Additionally, due to the lack of control, the influence of comprehensive treatment with TCM on hematological indicators could not be confirmed exactly, and further randomized controlled trials are needed to prove.
Conclusion
In conclusion, the clinical symptoms exhibited by patients after undergoing VATS for early-stage lung cancer primarily consist of lung-related symptoms, including dyspnea, cough, and phlegm. These symptoms are often accompanied by systemic manifestations, such as fatigue, and local discomforts, such as pain. A comprehensive treatment program utilizing TCM can effectively alleviate these prominent symptoms and enhance the QoL of patients, thus contributing significantly to their physiological recovery.
Supplemental Material
sj-docx-1-ict-10.1177_15347354241261977 – Supplemental material for Chinese Herbal Medicine Combined With Liuzijue Exercise in Physiological Rehabilitation After Video-assisted Lung Lobectomy for Cancer: A Prospective Propensity Score Matching Study
Supplemental material, sj-docx-1-ict-10.1177_15347354241261977 for Chinese Herbal Medicine Combined With Liuzijue Exercise in Physiological Rehabilitation After Video-assisted Lung Lobectomy for Cancer: A Prospective Propensity Score Matching Study by Ao Qi, Yiyun He, Yifeng Gu, Congmeng Zhang, Xiong Qin, Yichao Wang, Yong Yang, Jialin Yao, Huiling Zhou, Wenxiao Yang, Lingzi Su, Qin Wang, Jiajun Song, Lijing Jiao, Yabin Gong, Jiaqi Li and Ling Xu in Integrative Cancer Therapies
Footnotes
Acknowledgements
We thank all patients for participating in this study, completing data collection, and providing laboratory samples.
Authors’ Contributions
AQ, YYH, JQL drafted the paper, LX, YBG designed the study, LJJ critically revised the paper, YFG, CMZ, XQ, YCW, YY, JLY, HLZ, WXY, LZS, QW, JJS provided research materials, patients, laboratory samples, or other analytical tools. All authors read and approved the final manuscript.
Availability of Data and Material
All relevant data and materials are within the manuscript and its additional files.
Consent for Publication
All authors agree to publish this article.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Shanghai Science and Technology Commission “Science and Technology Innovation Action Plan” medical innovation research special project (No. 22Y31920400); Clinical Collaboration Pilot Project of Traditional Chinese and Western Medicine from Shanghai Municipal Health Commission (ZXYXZ-201901); Shanghai University of Traditional Chinese Medicine combined project (YYKC-2021-01-155); and National Natural Science Foundation of China (No. 82104948).
Ethics Approval and Consent to Participate
This project was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (No: 2020-038). All participants signed the informed consent before taking part in this study and any intervention.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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