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SARS: Clinical Trials on Treatment Using a Combination of Traditional Chinese Medicine and Western Medicine
(2004; 194 pages) View the PDF document
Table of Contents
View the documentAcknowledgements
View the documentIntroduction
View the documentReport of the International Expert Meeting to review and analyse clinical reports on combination treatment for SARS
View the documentReport 1: Clinical research on treatment of SARS with integrated Traditional Chinese medicine and Western Medicine
View the documentReport 2: Clinical efficacy of the treatment of SARS with integrated Traditional Chinese medicine and Western medicine: an analysis of 524 cases
View the documentReport 3: Manifestation of symptoms in patients with SARS and analysis of the curative effect of treatment with integrated Traditional Chinese medicine and Western medicine
View the documentReport 4: Clinical study on 103 inpatients undergoing therapy with integrated Traditional Chinese medicine and Western medicine
View the documentReport 5: Clinical observations of 11 patients with SARS treated with Traditional Chinese medicine
View the documentReport 6: Effects of applying integrated therapy with Traditional Chinese medicine and Western medicine on liver and kidney functions in patients with SARS
View the documentReport 7: Clinical research on 63 patients with SARS treated with integrated Traditional Chinese medicine and Western medicine
View the documentReport 8: Influence of integrated therapy with Traditional Chinese medicine and Western medicine on lymphocytes and T-lymphocyte subpopulations of patients with SARS
View the documentReport 9: Analysis of the clinical curative effects on patients with SARS of treatment with Traditional Chinese medicine and Western medicine
View the documentReport 10: Evaluation of clinical curative effects of Traditional Chinese medicine in treatment of patients convalescing from SARS
View the documentReport A: A herbal formula for the prevention of transmission of SARS during the SARS epidemic in Hong Kong Special Administrative Region - a prospective cohort study
View the documentReport B: Effects of Chinese medicine on patients convalescing from SARS in Hong Kong special administrative region - a prospective non-randomized controlled trial
View the documentReport C: Traditional Chinese medicine in the management of patients with SARS in Hong Kong Special Administrative Region - a case-control study of 24 patients
View the documentAnnex
 

Report 9: Analysis of the clinical curative effects on patients with SARS of treatment with Traditional Chinese medicine and Western medicine

Wang Rongbing34, Liu Junmin34, Jiang Yuyong34, Wu Yunzhong34, Wang Xiaojing34, Chi Pinpin34, Sun Fengxia34 and Gao Lianyi34

34 Beijing Ditan Hospital, Beijing 100011, People’s Republic of China


Abstract The objective was to observe how integrated treatment with Traditional Chinese medicine (TCM) and Western medicine affects major indices of the progress of severe acute respiratory syndrome (SARS), and to evaluate the curative effects of the integrated treatment with TCM and Western medicine. The study included 135 patients with clinically confirmed SARS of whom 68 were in the integrated treatment group and 67 in the control group. Patients in the control group received basic treatment with Western medicine, whereas patients in the integrated treatment group received herbal decoctions for relieving fever, removing toxins and eliminating dampness in addition to the same basic Western medicines as used in the control group. Both groups received a course of treatment of more than 2 weeks. Fever relief, cellular immunity, pulmonary inflammation, secondary infection and other curative effects were compared between the two groups after treatment. On days 2 and 3 after the start of treatment, the body temperature of patients in the control group was higher than that in patients in the integrated treatment group and the difference was significant (p < 0.01). The curve of decline in body temperature against time for patients in the group that received integrated treatment was relatively smooth; on day 20 after start of treatment, better cellular immunity and improvement in absorption of pulmonary inflammation were observed in the integrated treatment group. The statistical comparison between the two treatment groups revealed no significant differences in the time taken to absorb inflammation, cumulative dose of methylprednisolone, timing of administration and daily dose per person (p > 0.05). A decreasing tendency in the occurrence of secondary infection was seen in the integrated treatment group. Curative effects in the integrated treatment group were superior to those noted in the group treated with Western medicine alone in terms of gradual reduction of body temperature, mitigation of inhibition of cellular immunity and promotion of absorption of pulmonary inflammation.

Introduction

SARS is an acute infectious disease, caused by a newly found corona virus, with strong infectivity and a high mortality rate. Human beings are vulnerable to this disease and it presents a severe threat to health as well as affecting productivity. At present, studies on the microbiological characteristics and pathogenic mechanism of the SARS virus are still ongoing and no specific treatment is available. For the purposes of improving clinical curative effects, alleviating symptoms and mitigating the suppression of cellular immunity and severe inflammatory reaction during the course of disease, we treated 68 SARS patients with integrated TCM and Western medicine and set up a control group of 67 cases treated concurrently with Western medicine alone. Satisfactory curative effects were obtained with both treatments, but treatment with the integrated therapy was more effective.

Methods

Study subjects

All the participants were patients with clinically confirmed SARS admitted to our hospital from 10 April 2003 to 26 May 2003. Twenty-seven male and 41 female patients, aged 18-56 years with an average age of 35 years, were included in the group treated with integrated traditional and Western medicine (treatment group). Thirty-six patients were classified as normal cases and 32 as serious cases. Twenty-three male and 44 female patients, aged 20-65 years with an average age of 38 years, were included in the group treated with Western medicine alone (the control group); 39 patients in this group were classified as normal cases and 28 as serious cases.

The criteria for clinical diagnosis, case classification and discharge from hospital were in conformity with the criteria for infectious atypical pneumonia promulgated by the Ministry of Health of the People’s Republic of China. The general clinical data and grouping of the patients are shown in Table 1.

Criteria for inclusion

The criteria conformed with those given in Clinical diagnosis criteria for infectious SARS (proposed) issued by the Ministry of Health; the patients included were aged 18-65 years and showed no sensitivity or allergic reactions to any of the medicines used.

Criteria for exclusion

Patients were not eligible for participation in the study if they:

• were aged < 18 years or > 65 years;
• had serious underlying diseases; or
• were pregnant or lactating.


Therapeutic regimens

The study subjects were allocated to seven different treatment zones according to the order of admission, and assigned to either the integrated treatment group or the group treated with Western medicine alone.

The basic treatment given to patients in both groups was identical to the therapeutic regimens recommended by experts from the SARS Command Centre of the Ministry of Health of the People's Republic of China. In our hospital, the usual dosage of methylprednisolone was 80-160 mg/day and the dose of ribavirin was 0.75 g-1.5 g/day for a course of 2 weeks. Other drugs administered were: azithromycin 0.5 g per day for 5 days; levofloxacin 0.4 g per day for 7 days; thymosin 100-200 mg per day; no limits were imposed on supportive treatment. All patients received oxygen through a nasal tube and ventilators were used when necessary.

Therapeutic regimens of TCM were administered in accordance with the recommendations of experts from the State Administration of Traditional Chinese Medicine.

In our hospital, Guoyao No. 2 was administered during the acute stage of disease. The main ingredients were Sypsum Fibrosum 30 g, Semen Armeniacae Amarum 10 g, Radix Scutellariae 10 g, Rhizoma Atractylodis 10 g, Rhizoma Pinelliae 10 g and Radix Arnebiae seu Lithospermi 15 g.

Guoyao No. 3 was used in the critical stage. The main ingredients were Cornu Bubali 30 g, Radix Rehmanniae 15 g, Radix Scrophulariae 15 g and Flos Chrysanthemi Indici 15 g.

For patients in whom the course of disease had exceeded 3 weeks, or patients in the convalescent stage, Guoyao No. 4 was administered. The main ingredients included Radix Adenophorae Strictae 15 g, Radix Ophiopogonis 15 g, Radix Salviae Miltiorrizae 15 g, Radix Paeoniae Rubra 10 g and Radix Panacis Quinquefolii 10 g, taken separately.

Each dose was decocted in 200 ml, and taken twice daily, 100 ml in the morning and 100 ml at night; i.e. one dose per day. The treatment period for the entire course of TCM was more than 2 weeks and the observation period was 3 weeks.

Criteria for discharge from hospital conformed to the Reference standard for the discharge of cases of infectious SARS issued by the Ministry of Health of the People's Republic of China.

Observations

In the course of treatment, symptoms and signs of all patients were recorded and physiochemical analysis was carried out before and after the treatment. The observations recorded included body temperature, results of routine blood tests, serum enzymogram, T-lymphocyte subpopulations, and results of examination of chest X-rays. Some of the patients were tested for SARS RNA and IgG in pharyngeal aspirate, blood and urine. These special tests were conducted by the national or Beijing Centre for Disease Control; the RNA test was carried out using the polymerase chain-reaction method, and an enzyme-linked immunosorbent assay method was employed for antibody tests; for the analysis of T-lymphocyte subpopulations, a flow cytometry method was used. All experiments were conducted by our hospital.

Statistical analysis

All data were subjected to statistical analysis, and the normal distribution, t-test, rank-sum test and X2 test were conducted.

Quality control

To ensure appropriate quality of clinical research, the researchers and physicians recording the observations were trained and suitably qualified. For each district, a professor was responsible for the implementation of the clinical research protocol. Two suitably qualified persons were elected to gather data which were delivered to the medical statistical department of the hospital for statistical analysis. The database and case research documents were checked by the research management staff of the hospital. All the herbal pieces used conformed to the standards in the Chinese Pharmacopoeia, (2000 Edition, Volume I), and the patent medicines used were all commercially available prescription drugs.

Results

General clinical information on patients

The distribution of age, sex and stage of disease of the patients in the two treatment groups and the clinical classification of the two groups was comparable, with no statistically significant difference. There were no statistically significant differences between the integrated treatment and the treatment with Western medicine alone with respect to positive rate of pathogenic inspection at the time of admission to the hospital and after 20 days, or in the lymphocyte counts and T-lymphocyte subpopulations (Tables 1-3).

Table 1. General clinical information on patients in the two treatment groups (mean ± SE)

Treatment group

Sex

Age
(mean ± SE)

Clinical type

Case distribution at each stage

Stage when patients were included in the groups (mean ± SE)

 

M

F

 

Serious

Normal

   

Integrated (TCM plus Western)

26

42

35.06 ± 1.27

32

36

37

29

2

6.46 ± 0.56

Western medicine

23

44

38.43±1.43

28

39

30

33

4

7.43 ± 0.50

p

0.721

0.129

0.605

0.439

0.252

 

M, Male; F, female; SE, standard error; TCM, Traditional Chinese medicine


Table 2. Results of test for SARS RNA in pharyngeal aspirate upon admission to hospital, and for SARS-corona virus-IgG in blood, and RNA in urine 20 days after hospitalization

Treatment group

Pharyngeal aspirate RNA

Blood IgG

Urine RNA

Integrated TCM plus Western medicine

No. tested

29

53

23

 

Positive (%)

18 (62.07)

39 (73.58)

1 (4.35)

Western medicine only

No. tested

25

17

8

 

Positive (%)

18 (72.00)

13 (76.47)

0

p

 

0.368

0.261

0.261

Table 3. Comparison of abnormal lymphocyte count and T-lymphocyte subpopulations of patients upon inclusion in a treatment group (mean ± SE)

 

Lymphocyte
(x 109/l)

CD3 (/µl)

CD4 (/µl)

CD8 (/µl)

Normal value

1-5

1032-2086

706-1125

323-886

Integrated treatment group

n = 40
0.67 ± 0.19

n = 63
451.68 ± 218.39

n = 66
256.97 ± 155.12

n = 55
163.75 ± 71.72

Western medicine alone

n = 42
0.65 ± 0.20

n = 56
491.39 ± 222.35

n = 60
283.72 ± 159.77

n = 48
188.52 ± 77.44

p

0.683

0.365

0.261

0.136

 

SE, Standard error


There was good comparability between patients in terms of lymphocyte count and T-lymphocyte subpopulation at the time of their inclusion in one of the treatment groups.

Influence on pyretolysis

Fever was the main manifestation of SARS; it lasted up to 2 weeks and was therefore one of the main targets of treatment. No significant difference between the treatment groups in terms of decrease in body temperature was seen before or after treatment, although the body temperature of patients in the control group was higher than that in the integrated treatment group 2 or 3 days after the start of treatment, and this difference was statistically significant (p < 0.01). A smooth curve for the decrease in temperature was observed in the integrated treatment group (Fig. 1).


Fig. 1. Changes in body temperature of patients in the two treatment groups

Influence on cellular immunity

After the onset of illness, concentrations of lymphocytes and T-lymphocyte subpopulations were seen to decrease significantly, and those patients who experienced a continuous decrease were generally seriously ill. The levels of lymphocytes recovered naturally during the convalescent stage. There was good comparability between the groups before the start of treatment, whereas 20 days after start of treatment, the integrated treatment showed better effects in protecting cellular immunity and promoting recovery (Fig. 2).


Fig. 2a. Change in lymphocyte concentration in patients in the two treatment groups before and after treatment


Fig. 2b. Change in concentration of CD3 cells in patients in the two treatment groups before and after treatment


Fig. 2c. Change in concentration of CD4 cells in patients in the two treatment groups before and after treatment


Fig. 2d. Change in concentration of CD8 cells in patients in the two treatment groups before and after treatment

Influence on the absorption of lung inflammation

A different extent of inflammation was seen in the lungs of individual patients, and various degrees of improvement or nearly total absorption of inflammation (as seen from X-ray examination), were observed 3 weeks after the start of treatment. There was good comparability between the states of illness of patients in the two groups as seen from X-rays obtained before treatment, yet the number of patients in the treatment group in whom inflammation was absorbed was obviously larger than that in the group treated with Western medicine 3 weeks after treatment, and no significant difference in the number of days needed for absorption of inflammation was observed (Table 4).

Table 4. Comparison of chest X-ray examination of patients in the two treatment groups

Treatment group

Pathogenic change in single lung lobe (n)

Pathogenic change in multiple lung lobes (n)

Complete absorption
(n)

Incomplete absorption
(n)

Days of absorption
(mean ± SE)

Integrated treatment (TCM plus Western medicine)

12

56

48

20

18.58 ± 1.00

Western medicine only

13

52

33

34

17.00 ± 1.08

p

 

0.825

 

0.014

0.153

 

SE, standard error; TCM, Traditional Chinese medicine


The absorption of pulmonary inflammation in the treatment group was better than that in the group treated with Western medicine.

Methylprednisolone treatment

The doses of methylprednisolone and number of days of administration to the study subjects are summarized in Table 5.

The cumulative dosage, number of days of administration and per capita daily dose of methylprednisolone for patients in the two treatment groups were relatively low, and no significant differences between the two treatment groups were observed (Table 5).

Table 5. Dose and number of days of administration of methylprednisolone in the two treatment groups (mean ± SE)

Treatment group

No of patients treated with methylprednisolone

Total dose of methylprednisolone
(mg)

No of days of administration per patient
(mg)

Daily dose of methylprednisolone
(mg)

Integrated treatment (TCM plus Western medicine)

51 (75%)

1466.86 ± 624.97

15.98 ± 4.69

91.79 ± 30.78

Western medicine only

48 (71.65%)

1823.54 ± 836.61

17.81 ± 7.20

102.39 ± 41.96

p

0.700

0.080

0.168

0.257

 

SE, Standard error; TCM, Traditional Chinese medicine


Secondary infection and complications

The course of SARS lasted for 4 weeks, during which impairment of the cellular immune system and administration of immunosuppressant led to secondary infection. The occurrence of secondary infection in the integrated treatment group was lower than that in the group treated with Western medicine alone (Table 6). As secondary infection was one of the causes of death in patients with SARS, reducing and controlling it would help to lower the case fatality rate.

Table 6. Secondary infection and outcome in the two treatment groups

Treatment group

Bacterial infection
n (%)

Fungal infection
n (%)

Haemorrhage in digestive tract
n (%)

Discharge criteria satisfied
n (%)

Deterioration

Death

Integrated (TCM plus Western medicine)

5 (7.4)

2 (2.9)

0 (0)

66 (97.1)

1

1

Western medicine only

9 (13.4)

5 (7.5)

4 (6.0)

58 (86.6)

2

7

p

0.191

0.274

0.058

0.031

   

Secondary infections and complications were fewer in the integrated treatment group, and the prognosis for patients in this group was superior to that for the patients who received treatment with Western medicine alone.

Discussion

Therapy with integrated traditional and Western medicine is a unique form of clinical medicine used in the People’s Republic of China. At present, the Chinese medicines that are usually combined with Western medicine to treat SARS are the TCMs for relieving heat, toxin and dampness and clearing away lung-heat, which have resulted in definite curative effects.

Because there is as yet no specific and effective treatment for infection with the SARS virus and the pathogenic mechanism of the disease has not yet been elucidated, medical treatment should be specific to the symptoms, and control the excessively strong immune reactions and potential complications. The TCM should be based upon an overall analysis of symptoms and signs, the cause, nature and location of the illness and the patient’s physical condition according to the basic theories of TCM. Successful treatment necessitates the integration of experience in treating epidemic febrile diseases in both ancient and modern times to develop prescription principles for different stages of the disease, taking the methods of relieving heat, toxin and dampness and clearing away lung-heat as the main basis for all stages of treatment. Suitable therapy with integrated traditional and Western medicine can combine the advantages of both TCM and Western medicine, overcome adverse drug reactions and promote overall curative effects.

Fever is the major manifestation of the disease. Adrenal cortical hormone was used in the treatment of most of the patients in both treatment groups. Because it brought down body temperature quickly, the antipyretic effect of pure herbal medicine could not be demonstrated. The smooth curve representing decrease in temperature over time in the integrated treatment group suggested that traditional herbal medicines were likely to inhibit the impairment of the immune system caused by the virus, alleviate inflammatory reactions and facilitate a smooth decrease in body temperature by means of an unknown mechanism. So far, treatment that includes TCM has been found safe and effective.

A significant decrease in lymphocyte concentration results from damage to the immune system that has a bearing not only on diagnostic significance but also on the prognosis of the disease. In our study, it was observed that the scale of the reduction in lymphocyte concentration was decreased and the increase in concentration during the convalescent period was enhanced by treatment with integrated traditional and Western medicine. This demonstrates the protective effects of TCM on lymphocytes and immune function, and against the suppressive effects of antagonistic hormone on cellular immunity. Our study also demonstrated the effects of TCM in maintaining stability of the internal environment of the organism, expelling pathogenic factors, strengthening body resistance and improving the stress reaction and immune function.

Comprehensive research on the pathogenic mechanism of SARS is being conducted. Blocking the progress of pathogenic change in the lung and promoting the absorption of inflammation are important therapeutic goals. Effectiveness in promoting absorption of lung inflammation was observed in the patients who received the integrated treatment. This was possibly due to the action of TCM in alleviating impairment of the immune system and in suppression of fibrosis and the effects on the restoration of tissues of using large doses of antagonistic hormone.

There are many causes of mortality in SARS patients, among which serious immune damage and secondary infection related to the use of hormone are important. Fungal infection, septicaemia, disseminated intravascular coagulation and other infectious syndromes may appear in patients at the advanced stage of the disease. In our study, the rate of occurrence of secondary infection and adverse reactions to hormone administration in the treatment group was observed to be lower than in the group treated with Western medicine alone. This showed that treatment with TCM did have certain effects in protecting the function of immune cells and in promoting the body’s ability to fight infection.

Traditional Chinese medicine has accumulated rich clinical experience and rational knowledge relevant to treating diseases caused by viral infection, reinforcing the idea that medical advice should be sought as quickly as possible to prevent pathogenic progress. The prescriptions used in our research, which were prepared by several specialists in TCM, were based on the experience accumulated since ancient times. They included medicinal ingredients to expel pathogens and toxin so as to strengthen and replenish qi and yin. We believe that the methods and curative effects of therapy with integrated traditional and Western medicine would be further improved by extending the research and developing a deeper knowledge of the disease together with optimization of therapeutic regimens.

Conclusion

Treatment with integrated TCM and Western medicine was found to be superior to that with Western medicine alone in alleviating inhibition of cellular immunity and ameliorating absorption of pulmonary inflammation. Its positive effects in reducing adverse reactions to hormone treatment, and the rates of secondary infection and complications were also indicated.

Acknowledgements

This paper is dedicated to clinical researchers working at the forefront of the fight against SARS, and thanks are due to the specialists who offered guidance on this research. Thanks are also due to the State Administration of Traditional Chinese Medicine and the Beijing Administration of Traditional Chinese Medicine for their valuable support.

 

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