Effects of Suhuang Zhike Capsule on Pulmonary Function,Blood Gas Analysis Index, Serum PCT and CRP Expression in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Ren Junqing (任君清)

Xuancheng People's Hospital, Anhui Province, 242000, China

ABSTRACT OBJECTIVE: To observe the effects of Suhuang Zhike Capsule on pulmonary function, blood gas analysis index, serum PCT and CRP expression in patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 88 patients with acute exacerbation of chronic obstructive pulmonary disease admitted to the Department of Respiratory Medicine, Xuancheng People's Hospital of Anhui Province from December 2014 to December 2016 were randomly divided into the observation group and the control group, with 44 cases in each group. The control group was given routine clinical treatment, and the observation group was given Suhuang Zhike Capsule on the basis of the treatment method of the control group. After 7 days' treatment,the improvement of lung function indexes were observed and evaluated before and after treatment (forced expiratory volume in one second (FEV1), forced expiratory volume occupancy in the 1st second percentage of vital capacity (FEVl/FVC), peak expiatory flow (PEF)), blood gas analysis index (Arterial oxygen partial pressure (PaO2) and arterial blood carbon dioxide partial pressure (PaCO2), oxygenation index (OI)) and serum cytokine levels (procalcitonin (PCT) and C reactive protein (CRP). RESULTS: The total effective rate of the observation group was significantly higher than that of the control group (P ＜ 0.05). The FEV1, FEV1/FVC and PEF in 2 groups were significantly increased after the treatment (P ＜ 0.05), and the above lung function indexes in the observation group were significantly higher than the control group (P ＜ 0.05). PaO2 and OI were significantly increased after the treatment (P ＜ 0.05), PaCO2 was significantly decreased after the treatment (P ＜ 0.05), and the improvement of above blood gas analysis indexes were significantly superior of the observation group than the control group (P ＜ 0.05). The serum PCT and CRP levels in 2 groups were significantly decreased after the treatment (P ＜ 0.05), and the improvement in the observation group were more significant than that in the control group (P ＜ 0.05). CONCLUSION: Suhuang Zhike Capsule can inhibit serum inflammatory cytokine levels in patients with acute exacerbation of chronic obstructive pulmonary disease, improve blood gas analysis indicators,and improve lung functions.

KEYWORDS: Chronic obstructive pulmonary disease; Acute exacerbation; Suhuang Zhike Capsule; Lung function; Blood gas analysis index; Procalcitonin; C-reactive protein

Chronic obstructive pulmonary disease(COPD) is a relatively common respiratory disease characterized by persistent airflow limitation.The airflow limitation is progressive, and the clinical symptoms are mainly dyspnea, oppression in chest, gasping, sputum, chronic cough, etc.,which can further evolve into pneumocardial disease or respiratory failure with high morbidity and mortality[1]. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important disease course in the development of COPD disease, which seriously affects the health conditions of COPD patients. Studies have shown that 25% COPD patients with decline in lung function can be attributed to AECOPD, and AECOPD can significantly accelerate the course of COPD,which is an independent risk factor for the death of COPD patients[2]. At present, the main purpose of western medicine treatment on AECOPD is to delay the deterioration of lung function, stabilize clinical symptoms and prevent complications. The treatment methods include dilating airway, preventing infection and inhibiting airway inflammation, while the overall efficacy is limited[3]. Traditional Chinese medicine believes that the pathogenesis of AECOPD is mostly the lung deficiency caused by chronic illness or the retention of turbid phlegm, causing the distention of lung qi. If the patients suffer the exogenous pathogens as well, it will lead to acute exacerbation or recurrent episodes, symptoms of cough, wheezing,expectoration and asthma, which will significantly aggravate in a short period of time. Suhuang Zhike Capsule is a kind of proprietary Chinese medicine based on the theory of wind cough and developed by the well-known Chinese medicine practitioner Chao Enxiang with decades of clinical experience.It has the functions of relieving sore throat and cough, dispelling wind and ventilating the lung,and is especially effective for coughing, bucking,and itching pharynx caused by the lung qi failing in dispersing and wind pathogen invading the lung as well as the worsen disease condition caused by factors like sudden cold air or shortness of breath. In recent years, reports on the treatment of AECOPD by Suhuang Zhike Capsule have emerged. Pulmonary function tests are important objective indicators for clinical assessment of airflow limitation. Blood gas tests help to determine the extent of AECOPD.Bacterial infection is an important pathological basis for AECOPD, while serum procalcitonin (PCT) and C-reactive albumin. (CRP) are sensitive indicators for clinical identification of bacterial infections.Therefore, in this study, the author used Suhuang Zhike Capsule to treat 44 cases of AECOPD. It is proposed to observe the changes of lung function index, blood gas analysis index and serum PCT and CRP expression before and after the treatment to explore the mechanism and clinical efficacy of Suhuang Zhike Capsule in treating AECOPD.

MATERIALS AND METHODS

Clinical materials

A total of 88 patients with AECOPD admitted to the Department of Respiratory Medicine, Xuancheng People's Hospital of Anhui Province from December 2014 to December 2016 were randomly divided into 2 groups, with an amount of 44 in each group. There are 39 males and 5 females in the observation group,ranging in age from 58 to 85, with an average age of(75.5±4.3), while the duration of COPD was 1 to 13 years, with the mean value of (6.5±1.1) years,and the duration of AECOPD was 0.5 to 5 days, with the mean value of (3.41±0.33) days. There were 40 males and 4 females in the control group, ranging in age from 60 to 85, with an average age of (75.3±4.2),while the duration of COPD was 1 to 14 years, with the mean duration of (6.8±1.0) years, and the course of AECOPD was 0.5 to 5.5 days, with the average duration of (3.44 ± 0.32) days. There were no significant differences in gender, age, and duration of disease between the 2 groups (P ＞ 0.05), which was comparable.

Diagnostic criteria

The western medicine diagnostic criteria refers to the diagnosis of COPD on Guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease (revision of 2013)[4]. The course of the disease is acute exacerbation: COPD patients with respiratory symptoms beyond the scope of daily variation, requiring for changes of the clinical treatment program, represented as cough, shortness of breath, expectoration, worsen gasping, the significantly increased amount of sputum, possibly accompanied by fever and other inflammatory reactions. Pulmonary function test: FEV1/FVC value＜70% after bronchodilator adoption. The diagnostic criteria for traditional Chinese medicine (TCM)syndromes refer to the regulation of phlegm-heat stasis type of Diagnostic and Efficacy Standards for TCM Syndrome[5]: cough, expectoration, yellow and turbid phlegm, shortness of breath, wheezing,attenuated breath sounds of both lungs, and audible dry and wet rales, red tongue, thin yellow tongue coating, floating rapid pulse.

Inclusion criteria

The patient's age ranged from 55 to 85, and the stage of the disease was acute exacerbation. The patient or the patient's family informed consent to the clinical trial related to the treatment. This study was approved by the hospital ethics committee.

Exclusion criteria

Those who had co-morbidity of severe insufficiency of important organs such as cardiac insufficiency, hepatic insufficiency, and renal insufficiency. Those with co-morbidity of serious lesion in blood system and immune system. Those combined with tuberculosis, bronchial asthma,bronchiectasis, silicosis, lung cancer, tuberculosis and other serious lung diseases. Those combined with diabetes mellitus, hypertension, malignant tumor,upper respiratory tract infection and asthma, and mental disease.

Therapeutic methods

The control group was given routine medical treatment, including Cefoperazone Sodium and Sulbactam Sodium (Shenzhen Zhijun Pharmaceutical Co., Ltd., production batch number: 20141103,specification: 1.5 g) (3.0 g/time, intravenous drip,1 time/12 h), low flow oxygen therapy (2 L/min),Aminophylline Injection (Sichuan Meida Kang Huakang Pharmaceutical Co., Ltd., production batch number: 14100826, specification 10 mL:0.25 g) (0.5 g/time, intravenous drip, 1 time/d),Ambroxol Hydrochloride Sodium Injection (Jiangsu Haosen Pharmaceutical Co., Ltd., production batch number: 20141004, specification 30 mg)(30 mg/time, intravenous drip, 2 times/d). On the basis of the treatment method of the control group, the observation group was given Suhuang Zhike Capsule(Yangzijiang Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd., production batch number:14071511, specification 0.45 g per capsule) for treatment, 3 capsules a time by oral administration, 3 times a day. The efficacy of the 2 groups was evaluated after 7 days of treatment.

Indicator

(1) Clinical efficacy: this study took the Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease[4]as accordance.Clinical control: after the treatment, clinical symptoms of cough, wheezing, expectoration, lung sounds,etc. completely or basically disappeared. Laboratory indicators such as leucocyte count, CRP and neutrophils completely got back to normal. Markedly effective: after the treatment, clinical symptoms of cough, wheezing, expectoration, lung sounds, etc.were significantly relieved. Laboratory indicators such as leucocyte count, CRP and neutrophils were significantly improved. Improvement: after the treatment, clinical symptoms of cough, wheezing,expectoration, lung sounds, etc. were relieved.Laboratory indicators such as leucocyte count, CRP and neutrophils had been improved for some extent.Invalid: after the treatment, clinical symptoms of cough, wheezing, expectoration, lung sounds, etc.did not be alleviated at all. Laboratory indicators such as leucocyte count, CRP and neutrophils did not be improved or even deteriorated. Total effective = clinical control + markedly effective + improved. (2) Pulmonary function indicators: the improvement of lung function indicators were determined before and after the treatment, including forced expiratory volume in one second (FEV1), forced expiratory volume in the 1stsecond (FEVl), percentage of forced expiratory volume in 1stsecond to forced vital capacity (FEVl/FVC) and peak expiratory flow (PEF). (3) Blood gas analysis index: the blood gas analyzer was used to detect the inhaled oxygen concentration (FiO2), arterial oxygen partial pressure (PaO2) and arterial blood carbon dioxide partial pressure (PaCO2) before and after the treatment, and calculate the Oxygenation Index(OI) =PaO2/FiO2. (4) Serum cytokine level test: a total of 5 ml fasting peripheral vein before and after the treatment has been taken, after corresponding processes, centrifuge at 3000 rpm for 10 minutes,separate serum, and detect the levels of serum procalcitonin PCT and CRP by enzyme-linked immunosorbent assay. The whole process is strictly in accordance with the operating instructions.

Statistical methods

Statistical analysis was performed by SSPS 22.0 statistical software. The measurement data was expressed by (x–±s), t test. Count data comparison was represented by n (%), χ2test. P ＜ 0.05 indicates significant difference.

RESULTS

Comparison of clinical effects between the 2 groups after the treatment

The clinical efficacy in observation group was significantly higher than that in the control group. The difference was statistically significant (P ＜ 0.05). See Table 1.

Table 1. Comparison of clinical effects between the 2 groups after the treatment (n (%))

Table 2. Comparison on lung function indexes of the 2 groups before and after the treatment (x–±S)

Table 3. Comparison on the change of blood gas analysis indexes of the 2 groups before and after the treatment (±S)

Table 3. Comparison on the change of blood gas analysis indexes of the 2 groups before and after the treatment (±S)

Note: 1) compared with the data before the treatment, P ＜ 0.05; 2) compared with the control group, P ＜ 0.05

The control group 44 Before the treatment 66.35±7.81 59.01±6.75 203.62±29.71 After the treatment 76.42±8.73① 52.27±6.19① 268.40±37.19①The observation group 44 Before the treatment 65.96±7.73 54.86±6.83 198.79±26.88 After the treatment 89.71±9.86①② 43.75±5.43①② 338.53±41.16①②

Comparison on lung function indexes of the 2 groups before and after the treatment

There was no significant difference in FEV1,FEV1/FVC and PEF between the 2 groups before the treatment (P ＞ 0.05). The FEV1, FEV1/FVC and PEF were significantly increased after the treatment (P ＜0.05), and the improvement of above lungs functional indicators in observation group were significantly higher than that of the control group (P ＜ 0.05). See Table 2.

Comparison on the change of blood gas analysis indexes of the 2 groups before and after the treatment

There was no significant difference in PaO2, PaCO2and OI between the 2 groups before the treatment (P ＞ 0.05).The PaO2and OI were significantly increased in the 2 groups after the treatment (P ＜ 0.05), and PaCO2was significantly decreased (P ＜ 0.05). Moreover, the improved degree of the above blood gas analysis indexes in the observation group were significantly higher than that of the control group (P ＜ 0.05). See Table 3.

Comparison on the levels of serum cytokine of the 2 groups before and after the treatment

There was no significant difference in serum PCT and CRP levels between the 2 groups before the treatment(P ＞ 0.05). The serum PCT and CRP levels were significantly decreased after the treatment (P ＜ 0.05), and the improved degree in observation group was significantly higher than that in the control group (P ＜ 0.05). See Table 4.

Table 4. Comparison on the levels of serum cytokine of the 2 groups before and after the treatment (x–±S)

DISCUSSION

AECOPD is an acute onset process, which refers to the acute exacerbation of respiratory symptoms in patients with COPD. The symptoms including cough, dyspnea, increased sputum, yellow and turbid sputum, are far exceeded than daily variation,and usually require changes in medicinal treatment guildlines[6]. The pathogenesis of AECOPD is very complex. The modern medical research has confirmed that mostly AECOPD is developed from respiratory virus infection, especially rhinovirus infection.Molecular biology techniques identified that over 60% of patients with AECOPD carried respiratory viruses, who showed more pronounced symptoms of airway inflammation comparing with patients without viral infection. In addition, the study also found that patients with stable COPD had bacterial colonization in the lower respiratory tract, and the bacterial load increased significantly during the acute exacerbation period. Bacterial infection is often secondary to viral infection rather than the origin of AECOPD[7].Therefore, respiratory virus infection and bacterial infection play important roles in the pathogenesis of AECOPD. In clinical treatment, appropriate antiinfective medicines should be adopted in time to prevent the development of the disease. Whether to use the antibiotics is determined according to the color and texture of the sputum, changes of body temperature and peripheral leucocyte counts,etc. of AECOPD patients. However, the above indicators lack of specificity, so that a biomarker or a group of biomarkers in helping clinical adoption on antibacterial drugs have clinical significance.Serum PCT and CRP are biomarkers found in clinical practice in recent years, and have high specificity and sensitivity for the diagnosis of bacterial infectious diseases. PCT is a calcitonin propeptide glycoprotein produced by thyroid C cells. Under normal physiological conditions, PCT is extremely low in the body (＜0.1 ng/ml), but after suffering from bacterial or endotoxin infection, a large amount of PCT will be secreted by liver monocytes, macrophages,tissue lymphocytes of gastrointestine and lung, and endocrine cells, resulting in a significant increase of serum PCT levels, which will gradually decrease with the control of infection. CRP is an acute phasereactive protein synthesized by the liver. It presents in the body in a trace form under normal physiological conditions. Its level will be significantly increased when it is infected by bacteria, which can be several thousand times higher than the normal level. Under normal circumstances, when the CRP level exceeds 20 mg/L, there might be a presence of bacterial infection[8]. With the control of infection and the recovery of the disease, the CRP level will also decrease rapidly.The results of this study shows that the serum PCT and CRP were significantly higher than normal before the treatment, while were significantly decreased after the treatment, which suggests that detecting serum PCT and CRP levels are helpful to determine whether there is bacterial infection in AECOPD patients. It has an important clinical significance in guiding the rational adoption of antibiotics, evaluating the prognosis of AECOPD and directing anti-infective therapy[9].

COPD belongs to the category of "lung inflation", "hepatitis syndrome" and "cough" in TCM.Chinese medicine believes that the lung is delicate zang-organ, governing diffusion, purification and descent. Diffusion refers to transmitting the essence of the foods, and nourishing the skin, the hair, and the whole body. The purification and descent is clearing and falling of lung qi. The lungs locate on the top of internal organs, and the lung qi is calm and descending. If people suffering the wind pathogen,upward disturbance of the wind-heat, the lung failing to diffuse and purify as well as the lung qi failing to descend, it will cause asthma, cough and adverse rising of lung qi. The patients in this study are mostly vulnerable senior citizens, the viscera and qi are deficient, and the lungs have been exposed to exogenous evil for a long time. As a result, the lung qi is damaged, and the spleen fails to transport,causing food and drink being difficult to become essence. The phlegm and body fluid stuffed deep inside the lungs, causing the deficiency of both the lung and the spleen. According to the principle of"treat the exterior syndrome first for acute onset", on the one hand, the treatment should be dispellig windevil and cold, on the other hand, ventilating the lung and relieving the cough to eliminate the root cause of the disease. Suhuang Zhike Capsule consists of 9 kinds of material medica. In this formula, ephedra is used for ventilating lung, relieving cough and asthma. Perilla leaves relieving exterior syndrome,dispelling cold, and ventilating lung qi to dissipate phlegm. Earthworm is used for clearing lung-heat and relieving asthma. Honeyed folium eriobotryae is used for clearing the lung and relieving cough, descending adverse qi and reducing vomiting. Perilla fruit is used for relieving cough and asthma, descending adverse qi and eliminating phlegm. Cicada slough is used for clearing wind-heat, relieving sore throat and producing sound. Hogfennel root is used for clearing heat and dispelling wind, descending adverse qi and resolving phlegm. Great burdock achene is used for dispelling wind-heat, ventilating lung qi,relieving sore throat, and removing toxicity for detumescence. Chinese magnoliavine fruit is used for astringing lung and promoting production of fluid, nourishing yin and securing essence. All these material medica are compatible with each other in dispelling the wind and cold, as well as ventilating lung qi for relieving cough. Modern pharmacological studies have shown that ephedrine volatile oil has a good effect on sweating, and ephedrine has a significantly antiasthmatic effect by exciting α-adrenergic receptors, relaxing bronchial smooth muscle, promoting the release of norepinephrine and adrenaline, and inhibiting the release of allergic transmitters[10]. Perilla can effectively alleviate symptoms of oppression in chest, shortness of breath,wheezing, cough, etc. in asthma patients. It has good effects on antitussive, antiasthmatic and expectorant.Perilla leaves can strongly inhibit many pathogenic bacteria such as Staphylococcus aureus and Escherichia coli[11]. Succinic acid and hypoxanthine in earthworm can effectively inhibit airway remodeling in asthma patients, and have anti-asthmatic and antitussive effects[12]. Cicada slough has a function of expelling phlegm, antitussive, antispasmodic and antiasthmatic by improving the number of leucocyte and microscopic blood stasis[13]. The extraction of hogfennel root with white flowers has a certain inhibitory effect on experimental cough in mice.It can relax bronchial smooth muscle, resisting allergic medium release with an obvious calcium ion antagonistic activity, and has a definite therapeutic effects on respiratory tract infection[14]. Chinese magnoliavine fruit has functions of bacteriostasis,anti-fatigue, anti-aging, enhancing immunity, etc.

As mentioned above, bacterial infection is an important pathological basis of AECOPD. Serum PCT and CRP are sensitive indicators for clinical identification of bacterial infections. The results of this study showed that serum PCT and CRP levels were significantly decreased after the treatment,and the decreased degree were significantly lower than that in the control group, which suggested that Suhuang Zhike Capsule can inhibit the development of AECOPD by decreasing serum PCT and CRP levels. Pulmonary function tests are of great value for com firming air flow limitation and are the very standard for clinical diagnosis of COPD. After the adoption of bronchodilators, FEVl/FVC ＜ 70% indicates that the patient has air flow limitation and cannot be completely reversed. The results of this study showed that both groups had a pre-treatment FEV1/FVC of ＜ 70%, and the data were significantly increased after the treatment,while FEVl/FVC ＞ 70% for all patients in the observation group. In addition, the FEV1and PEF levels in the observation group were significantly higher than that in the control group after the treatment, which suggests that Suhuang Zhike Capsule can effectively improve lung function in patients with AECOPD. The detection of blood gas analysis indicators is helpful to judge the degree of disease development of AECOPD patients.PaO2, PaCO2 and OI are common blood gas analysis indicators. The results of this study showed that PaO2 and OI were significantly increased and PaCO2 was significantly decreased after the treatment. Moreover,the improvement degree of blood gas analysis indexes above in the observation group was significantly higher than that of the control group, which suggests that Suhuang Zhike Capsule can effectively improve the blood gas analysis indexes of AECOPD patients. In summary, Suhuang Zhike Capsule has certain effects on inhibiting serum inflammatory cytokine levels in patients with acute exacerbation of chronic obstructive pulmonary, improving blood gas analysis indicators,and improving lung functions.