Clinical Effect of Yinma Zhisou Decoction Combined with Western Medicine in the Treatment of Acute COPD (Stagnation of Phlegm-Dampness in Lung)

Caixia SHAN,Jing ZHANG, Li YANG, Shihong XU, Yaonan DU, Jun DU*

Nanchong Chinese Medicine Hospital, Nanchong 637000, China

Abstract [Objectives] To explore the effectiveness and safety of Yinma Zhisou Decoction in the treatment of AECOPD with phlegm-heat obstructing lung syndrome, and observe the symptoms of Yinma Zhisou decoction in the treatment of AECOPD patients with phlegm-heat stagnation lung syndrome improvement, inflammatory indicators, lung function, blood gas analysis, etc. [Methods] A total of 92 cases who met the inclusion criteria and exclusion criteria were included in the study according to 1∶1 were randomly divided into treatment group and control group, control group with conventional Western medicine treatment, the treatment group on the basis of control group with Yinma Zhisou decoction treatment, a course of 10 d. The changes in TCM syndrome score, arterial blood gas analysis, pulmonary function, serum inflammatory indicator, mMRC score, and the CAT scores between the two groups after treatment were observed. All collected data were statistically analyzed with SPSS 26.0. [Results] (i) Comparison of the curative effect between the two groups. After treatment, the total effective rate of the treatment group was 93.5%, which was higher than that of the control group (76.1%, P<0.05). The curative effect of the treatment group was better than that of the control group (P<0.05). (ii) Comparison of single TCM symptom scores. After treatment, the single TCM symptom scores of the two groups were lower than before (P<0.05), but the improvement of wheezing, cough, phlegm and chest pain in the treatment group was better than that in the control group (P<0.05). There was no significant difference in the improvement of wheezing sound (P>0.05), but there was a trend of difference. (iii) Comparison of mMRC score and CAT score between the two groups. After treatment, the mMRC score and CAT score of the two groups were significantly improved (P<0.05), and the difference was statistically significant. (iv) Comparison of blood gas analysis indicators between the two groups. Intra-group comparison after treatment: PaO2 of the control group and the treatment group after treatment was significantly improved compared with that before treatment (P<0.05), and the difference was statistically significant. Comparison between the two groups after treatment: PaO2 and PaCO2 of the two groups after treatment (P>0.05), and the difference was not statistically significant. It indicated that Yinma Zhisou decoction had more advantages in improving hypoxia. (v) Comparison of pulmonary function between the two groups. After treatment, the FEV1/FVC of the treatment group and the control group was significantly different (P<0.05), and there was a statistical difference (P<0.05). (vi) Comparison of inflammatory indicators between the two groups. Intra-group comparison after treatment: the inflammatory indicators WBC, CRP and PCT in the control group and the treatment group were significantly lower than before treatment (P<0.05), and the differences were statistically significant. It indicated that Yinma Zhisou decoction could effectively control inflammation and reduce inflammation reaction. [Conclusions] Compared with the control group, Yinma Zhisou decoction has obvious advantages in improving cough, expectoration and wheezing, and can significantly improve the total effective rate. Compared with Western medicine alone, Yinma Zhisou decoction can significantly improve patients’ hypoxia, reduce mMRC and CAT scores, improve body activity tolerance, improve airway symptoms, and significantly reduce WBC, CRP, PCT and other serum inflammatory indicators. It can be seen that Yinma Zhisou decoction combined with Western medicine treatment is obviously better than simple Western medicine treatment, the curative effect is better, and the safety is better, and there are no serious adverse reactions in the course of the trial.

Key words Acute aggravation of COPD, Yinma Zhisou decoction, Stagnation of phlegm-dampness in lung, Traditional Chinese medicine

1 Introduction

Chronic obstructive pulmonary disease (COPD) is a disease induced by airway or alveolar closure caused by toxic particles or gases and other complex factors, resulting in persistent respiratory symptoms and airflow limitations. It is the fourth major disease causing death in the world[1], the number of COPD patients reached 384 million in 2010, and the global incidence rate was 11.7%[2]. The disease is mainly characterized by repeated cough, expectoration and shortness of breath all the year round, and finally complicated with respiratory failure, cor pulmonale and other critical diseases. It not only causes the decline of patients’ quality of life and physical and mental anxiety, but also brings unbearable economic pressure. Clinical Western medicine treatment adopts glucocorticoid (ICS), antibiotics, expectorant and other drugs, and long-term use of antibiotics not only produces drug resistance and double infection, and but also makes the disease incurable and easy to repeat. According to the investigation of the current situation, it is found that the treatment with traditional Chinese medicine has great clinical advantages in improving the quality of life and pulmonary function of patients, improving respiratory muscle fatigue and malnutrition, regulating immunity and other mechanisms. Lung distension is a complex syndrome of deficiency and excess. The most common signs are exogenous six climatic exopathogens and phlegm and blood stasis. According to the etiology and pathogenesis of the disease, the onset period is marked by the accumulation of phlegm, heat and blood stasis. Therefore, syndrome differentiation and treatment should be carried out according to the characteristics of symptoms. This study summed up the treatment method using Yinma Zhisou decoction for clearing heat and resolving phlegm, relieving cough and relieving asthma, promoting blood circulation and benefiting qi, and harmonizing the spleen and stomach. It was found that the clinical effect of Yinma Zhisou decoction was remarkable. The clinical efficacy of Yinma Zhisou decoction in the treatment of COPD with stagnation of phlegm-dampness in lung is reported as follows.

2 Data and methods

2.1 Objects of studyPatients with COPD with stagnation of phlegm-dampness in lung admitted to the Respiratory Department of Nanchong Chinese Medicine Hospital from July 2019 to September 2020 were selected. In this study, 96 patients with stagnation of phlegm-dampness in lung were included in the clinical trial, and 92 patients had complete data, with 46 cases in the treatment group and 46 cases in the control group. There were 36 males and 10 females in the treatment group, with an average age of (72.59±9.128) years; there were 32 males and 14 females in the control group, with an average age of (76.76±8.875) years. In terms of disease level, in the treatment group, there were 16 cases of grade I, 22 cases of grade II and 8 cases of grade III; in the control group, there were 13 cases of grade I, 28 cases of grade II and 5 cases of grade III. There was no significant difference in clinical data between the two groups (P>0.05).

2.2 Inclusion and exclusion criteria

2.2.1Diagnostic criteria. The diagnosis of COPD was made according to the 2019 edition of theGlobalInitiativeforChronicObstructiveLungDisease(GOLD)andtheGuidelinefortheDiagnosisandTreatmentofChronicObstructivePulmonaryDiseaseby the Chronic Obstructive Pulmonary Disease Group of the Respiratory Branch of Chinese Medical Association. Refer to the 2011 edition ofTCMDiagnosisandTreatmentGuidelineforChronicObstructivePulmonaryDiseaseformulated by the Chinese Society of Traditional Chinese Medicine.

2.2.2Inclusion criteria (those that meet all of the following conditions). (i) Meet the diagnostic criteria of Western medicine, traditional Chinese medicine and syndrome. (ii) The age is between 40 and 80 years old. (iii) The clinical severity of COPD is between grade I and III, and the course of disease is in the phase of acute exacerbation. (iv) The subject or the client or the subject’s family members knew and voluntarily signed the informed consent form.

2.2.3Exclusion criteria (those that meet any of the following conditions). (i) Complicated with bronchial asthma and bronchiectasis and other chronic lung diseases which have great influence on traditional Chinese medicine syndrome. (ii) Patients with severe respiratory failure, pulmonary encephalopathy or artificial mechanical ventilation (non-invasive or invasive), reluctant to offer syndrome information. (iii) Patients with serious primary diseases and neuropsychosis of other organs such as heart, brain, liver, and kidney. (iv) Patients with chronic cough and wheezing caused by fungi, tuberculosis, tumor, irritating gas, silicosis, allergy and other factors after being confirmed by examination. (v) Those who are allergic to many kinds of drugs. (vi) Those who routinely used immunomodulators for more than one month within 6 months. (vii) Pregnant or lactating women.

2.2.4Criteria for dropping out and elimination of cases. Those who do not meet the inclusion criteria or do not use drugs according to the provisions of the program after inclusion shall be excluded. Those who quit or fail to complete the whole course of treatment and affect the curative effect are regarded as cases of dropping out.

2.3 Method designThe patients were randomly divided into treatment group (n=46) and control group (n=46). The control group was given oxygen therapy (2 L/min), Western medicine antibiotics, hormones, bronchodilators and anticholinergic drugs. The treatment group used the former combined with Yinma Zhisou decoction (honeysuckle 15 g, ephedra 5 g, almond 15 g, root of balloonflower 15 g, gypsum 30 g, root of large-flowered skullcap 15 g, rhizome of Chinese goldthread 10 g, aster 30 g, coltsfoot flower 15 g, tuber of stemona 15 g, polygala root 15 g, Chinese fever vine 30 g, amomum fruit 10 g, Japanese ardisia herb 30 g, vladimiria root 10 g, honey-fried licorice root 6 g). All the above drugs were decocted with water and 100 ml of decoction was taken orally for 3 times each time. The course of treatment in both groups was 10 d.

2.4 Evaluation of efficacy and safety

2.4.1Index comparison. (i) The changes of leukocyte, C-reactive protein, procalcitonin (PCT), blood gas and liver and kidney function were compared between the two groups before and after treatment. 5 mL of MCP-1 blood samples were collected, and the detection method was enzyme-linked immunosorbent assay (Elisa). All were completed by the Clinical Laboratory of Nanchong Chinese Medicine Hospital. (ii) The pulmonary function indexes of the two groups before and after treatment were measured and compared, including 1 s forced expiratory volume (FEV1) and 1 s forced expiratory volume to forced vital capacity (FEV1/FVC). (iii) The improvement of symptoms was observed by dyspnea scale (mMRC) and COPD Assessment Test (CAT). (iv) It was based on TCM syndrome to calculate the total score of TCM syndrome, curative effect index, single score of TCM syndrome, cough, expectoration, wheezing, chest tightness, lung rale (from mild to severe, the higher the score, the more serious the disease).

2.4.2Evaluation of curative effect. Refer to theGuidingPrinciplesofClinicalResearchonNewChineseMedicine.(GuidingPrinciplesofClinicalResearchonNewChineseMedicine—Zheng Xiaoyu as Editor-in-Chief). Reduction rate of syndrome score=(Pre-treatment syndrome score-Post-treatment syndrome score)/Pre-treatment syndrome score×100%. Clinical symptoms and signs disappear or basically disappear, and the decrease of syndrome score > 95%—clinical control; clinical symptoms and signs are significantly improved, and the decrease of syndrome score > 70%—marked; clinical symptoms and signs are improved, and the decrease of syndrome score > 30%— effective; there is no significant improvement in clinical symptoms and signs, or it is even aggravated, and the decrease of syndrome score < 30%—ineffective.

3 Results and analysis

3.1 Comparison of TCM syndrome scoreTable 1 showed that in the treatment group, except for the improvement of pulmonary wheezing, the differences in other symptoms were statistically significant before and after treatment (P<0.05). The improvement of cough, expectoration, wheezing and chest tightness and the total score of symptoms in the treatment group were significantly better than those in the control group (P<0.05).

Table 1 Comparison of individual scores of TCM symptoms between the two groups (points,

3.2 Comparison of curative effect of traditional Chinese medicineAs can be seen from Table 2, the total effective rate of the treatment group was 93.5%, and the total effective rate of the control group was 76.1%. After treatment, there was a significant difference in the curative effect of TCM syndrome between the two groups (P<0.05). The effect of the treatment group was significantly better than that of the control group.

Table 2 Comparison of the curative effect on TCM symptoms between the two groups (points,

3.3 Comparison of inflammatory indicatorsAs can be seen from Table 3, the inflammatory indicators WBC, CRP and PCT in the control group and the treatment group after treatment were significantly lower than those before treatment (P<0.05).

Table 3 Comparison of inflammatory cells between the two groups (points,

3.4 Comparison of dyspnea score and CTA score between the two groupsAs can be seen from Table 4, the dyspnea score and CAT score of the two groups were significantly improved after treatment (P<0.05). The dyspnea score and CAT score were significantly improved in the two groups after treatment (P<0.05).

Table 4 Comparison of dyspnea score and CTA score between the two groups (points,

3.5 Comparison of pulmonary function between the two groupsTable 5 showed that the FEV1/FVC of the two groups was significantly improved after treatment, and the difference was statistically significant (P<0.05).

3.6 Comparison of arterial blood gas between the two groupsAs can be seen from Table 6, the PaO2of the patients in the control group and the treatment group was significantly improved after treatment, and the difference was statistically significant (P<0.05). There was no significant difference in PaO2and PaCO2between the two groups before and after treatment (P>0.05).

Table 5 Comparison of pulmonary function between the two groups (%,

Table 6 Comparison of PO2 and PCO2 between the two groups (mmHg,

4 Discussion

According to the current treatment standard of COPD, the main treatment method of Western medicine is the early use of antibiotics, but the antibiotic resistance rate has been increasing for a long time, and repeated long-term antibiotic exposure not only causes the abuse of antibiotics and drug resistance, but also causes a lot of adverse drug reactions, resulting in aggravated infection and even death. Therefore, the problem of infection has become the biggest problem for clinicians. At present, according to the course of the development of traditional Chinese medicine, it is found that there are excellent physicians and schools in each period, and each physician continues to practice, which makes the theoretical basis more and more perfect, so that traditional Chinese medicine continues to move forward. However, the concept of preventive treatment of disease in traditional Chinese medicine is still of great guiding significance for early detection and treatment of modern diseases. And traditional Chinese medicine has its natural clinical advantages, and more and more researchers have found that there are irreplaceable advantages that Western medicine does not have. According to the investigation of the current situation, it is found that the treatment with traditional Chinese medicine has great clinical advantages in improving the quality of life and pulmonary function of patients, improving respiratory muscle fatigue and malnutrition, regulating immunity and other mechanisms. At the same time, it is found that traditional Chinese medicine has broad-spectrum bactericidal effect and can inhibit airway mucus secretion[3-4]. The treatment with integrated traditional Chinese and Western medicine has its unique advantages in the existing clinical treatment, such as reducing drug side effects, improving symptoms and psychological intervention, so as to effectively reduce patients’ pain and anxiety.

COPD is classified as "lung distension and cough" in traditional Chinese medicine, and it is considered to be a complex syndrome with deficiency and excess. The deficiency in origin is mainly characterized by the deficiency of lung, spleen and kidney, while the most common signs are exogenous six climatic exopathogens and phlegm and blood stasis. In this study, the investigation on the distribution of TCM syndrome types of COPD found that most of the patients developed COPD with stagnation of phlegm-dampness in lung. According to the etiology and pathogenesis of the disease, the onset period is marked by the accumulation of phlegm, heat and blood stasis. After consulting the literature, it was found that[5], Ban Chengjun, Li Yuanyuan, Xie Yanmingetal.observed more than 330 000 cases and found that phlegm-heat syndrome was the most common syndrome type in the acute stage of AECOPD. Wang Shengetal.[6]summed up four syndrome types: phlegm-heat obstructing the lung, abnormal rising of the lung-qi, deficiency of lung-spleenqiand turbid phlegm obstructing lung, among which phlegm-heat obstructing the lung and abnormal rising of the lung-qiwere the most common. Through cluster analysis of the distribution of TCM syndrome types of COPD, Huang Jinrong[7]found that phlegm-heat and turbid phlegm were the main signs in the acute stage, and with the increase of the course of disease and age, the impairment of viscera was mainly accompanied by deficiency syndrome. Therefore, based on the study of this subject, reviewing the investigation of TCM syndrome types of inpatients with COPD in our department in the past 3 years, it was found that stagnation of phlegm-dampness in lung, phlegm and blood stasis blocking the lung, spleen and lungqideficiency, lung and kidneyqideficiency were the main syndromes, among which stagnation of phlegm-dampness in lung accounted for the highest percentage. The treatment was mainly to clear heat and resolve phlegm, relieve cough and asthma. Maxing Shigan decoction comes from Treatise on Febrile Diseases, which has the function of clearing away lung-heat to relieve asthma. On this basis, Yinma Zhisou decoction was composed of honeysuckle, root of balloonflower, root of large-flowered skullcap, rhizome of Chinese goldthread, aster, coltsfoot flower, tuber of stemona, polygala root, Chinese fever vine, amomum fruit, Japanese ardisia herb, and costustoot. According to the theory of "phlegm-heat and blood stasis runs through lung distension", Xu Shihong, director of traditional Chinese medicine in Nanchong Chinese Medicine Hospital, used the method of clearing heat and promoting blood circulation to treat patients with COPD with stagnation of phlegm-dampness in lung. It was found that this prescription could effectively reduce cough, shortness of breath and other symptoms, reduce the amount of phlegm. At the same time, it could also improve appetite, and achieved remarkable results in clinical practice.

The honeysuckle in Yinma Zhisou decoction was cold, sweet, and could be used to treat the diseases related to lung, heart and stomach, with effects of heat-clearing and detoxification, dispelling the wind and heat from the body. Maxing Shigan decoction had the effect of relieving pungent coolness and relieving asthma. Aster and coltsfoot flower were warm in nature, bitter and pungent, which could be used for moistening lung qi, eliminating phlegm and relieving cough. The rhizome of Chinese goldthread and root of large-flowered skullcap had the effects of clearing away pathogenic heat and dampness, and purging intense heat and detoxicating. The root of balloonflower had the effect of resolving phlegm and relieving cough, relieving sore-throat to recover voice, promoting lung qi, expelling pus and eliminating carbuncle. The tuber of stemona had the effect of moistening lungqiand relieving cough. The Chinese fever vine had the effect of dispelling wind and dehumidification, promoting digestion and relieving stasis, detoxification and detumescence, promoting blood circulation and relieving pain. The amomum fruit and costustoot had the effect of promoting circulation ofqiand relieving pain. The Japanese ardisia herb had obvious effects in resolving phlegm and relieving cough, promoting blood circulation and removing phlegm and relieving cough and asthma. The whole prescription focused on clearing heat and resolving phlegm, relieving cough and relieving asthma, promoting blood circulation and supplementing the vital energy, and harmonizing the spleen and stomach for treatment. This prescription not only paid attention to clearing heat, but also paid attention to clearing phlegm and blood stasis, and treated AECOPD with stagnation of phlegm-dampness in lung by clearing away heat and resolving phlegm, promoting blood circulation and relieving asthma. The results showed that in the treatment group, in addition to the wheezing rale, the symptoms of cough, expectoration, wheezing and chest tightness were significantly improved, and the effective rate was 93.5%. It showed that Yinma Zhisou decoction could quickly relieve the clinical symptoms of acute COPD, improve the quality of life of patients, and the clinical application was safe and effective, which was worthy of clinical application.

The sputum of patients with COPD was significantly higher than that of normal people, which was mainly related to the excessive release of inflammatory mediators in the inflammatory reaction and a series of inflammatory reactions caused by the activation of leukocytes in the airway. Serum CRP is an inflammatory lymphokine that stimulates the synthesis of liver and epithelial cells. In the experiment, it was found that it could bind with the capsule C-polysaccharide of Streptococcus pneumoniae, bind with the phosphocholine on the membrane in the presence of calcium ion, bind with chromatin, activate the classical pathway of complement, enhance leukocyte phagocytosis, and promote the production of macrophage tissue factor. Procalcitonin (PCT) has been widely used as an important reference index for the diagnosis and treatment of bacterial infectious diseases. When bacterial infection occurs, macrophages and monocytes in liver, lymphocytes and endocrine cells in lung and intestinal tissues synthesize and secrete a large quantity of PCTs under the action of endotoxin, tumor necrosis factor-α and IL-6, which leads to a significant increase in serum PCT level. The results showed that the inflammatory indexes WBC, CRP and PCT in the treatment group were significantly lower than those before (P<0.05). It indicated that Yinma Zhisou decoction could effectively control infection and reduce inflammatory reaction in the treatment of acute exacerbation of COPD. According to modern pharmacological studies, honeysuckle had antipyretic, anti-inflammatory and antiviral effects, and its effective components had different inhibitory effects on inflammatory factors (NO, tumor necrosis factor and interleukin-6) produced by macrophages stimulated by LPS[8]. The modern pharmacological efficacy of Maxing Shigan decoction also had good anti-inflammatory and antipyretic, antitussive, and antiviral effects[9], and could inhibit the synthesis of prostaglandins, thus reducing nitric oxide, and playing the role of anti-inflammation and pain relief[10]. The root of balloonflower could reduce inflammatory factors (such as IL-8, CRP, TNF-α), thus inhibiting the inflammatory response[11]. The root of large-flowered skullcap could significantly reduce the content of myeloperoxidase (MPO), nitrogen oxide (NO) and the expression of related inflammatory factors, reduce the expression of IL-33, and reduce the occurrence of drug resistance[12]. The active components of coltsfoot flower were involved in 18 targets such as interleukin-2 (IL-2), cyclooxygenase-2 (COX-2), human ribonuclease A3 (RNASE3) and signal transduction-inflammation-energy metabolism-related biological processes and metabolic pathways[13], and it could be combined with aster to have antitussive effect.

The anti-inflammatory effects of tuber of stemona and Chinese fever vine were all related to NF-κB, TNF, mitogen activated protein kinase (MAPK) signal pathway[14-15]and so on. At the same time, this prescription had a certain degree of anti-inflammatory and bacteriostatic effect, and could effectively alleviate the inflammatory reaction, reduce the level of inflammatory factors, and significantly improve the injury of lung function.

The results showed that compared with the control group, Yinma Zhisou decoction had obvious advantages in improving cough, expectoration, wheezing and wheezing rale, improving the overall symptoms and signs of patients, and significantly improving the total effective rate of treatment. Compared with simple Western medicine treatment, Yinma Zhisou decoction could significantly increase PaO2, improve hypoxia, reduce mMRC and CTA scores, improve exercise tolerance, improve dyspnea, and improve the quality of life of patients. It can be combined with Western medicine to improve the anti-inflammatory and antibacterial effects, reduce the level of inflammatory factors, with high safety, so it is worthy of clinical application.