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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 8: Influence of integrated therapy with Traditional Chinese medicine and Western medicine on lymphocytes and T-lymphocyte subpopulations of patients with SARS

Li Jun33, Li Shaodan33, Liu Jinchao33, Wang Fusheng33, Du Ning33, Dong Yi33, Yang Yongping33 and Xiao Xiaohe33

33 No. 302 Hospital of PLA Beijing 100039, People’s Republic of China


Abstract The objective was to study how integrated therapy with Traditional Chinese medicine (TCM) and Western medicine regulated the immune function of the body by analysing its effects on lymphocytes and T-lymphocyte subpopulations in patients with severe acute respiratory syndrome (SARS). Forty-seven patients with SARS were randomly allocated to either the integrated treatment group or the group treated with Western medicine for a treatment course of 3 weeks. Levels of lymphocytes and subpopulations of T-lymphocytes, CD3, CD4/CD8, were measured in peripheral blood before and after treatment. Before treatment, the absolute level of lymphocytes in the peripheral blood of 38 of the patients was low, and a decrease in percentages of CD3, CD4/CD8 was observed in 19 cases. Comparison of the difference in the absolute value of peripheral lymphocytes in the two treatment groups before and after treatment showed a statistically significant difference (p <0.01), and the integrated treatment was superior to the treatment with Western medicine alone in this respect. Before treatment, there were 19 patients with extremely low CD3 levels (9 in the integrated treatment group and 10 in the group treated with Western medicine alone). After treatment there were two and eight cases in the integrated treatment group and the group treated with Western medicine alone, respectively. The numbers of patients with extremely low levels of CD4/CD8 before treatment were 15 and 13 in the integrated treatment group and the group treated with Western medicine, respectively and the numbers after treatment were 5 and 10, respectively. Fisher’s exact test was used for statistical analysis. The integrated treatment was obviously superior to the treatment with Western medicine alone in promoting recovery of T-lymphocyte subpopulations (p <0.05). The integrated treatment was obviously superior to the treatment with Western medicine alone in alleviating inhibition of lymphocyte activity, raising the level of T-lymphocyte subpopulations and enhancing immune function.

Introduction

SARS is a disease of the respiratory system with strong infectivity and a high mortality rate caused by a corona virus subtype (SARS virus) (1). There is currently no specific treatment available for this disease. Based on a summary of the general clinical characteristics of SARS patients and a prospective study design in which subjects were randomly allocated to either the “experiment” group or the control group, we studied integrated treatment with TCM and Western medicine and its ability to alleviate inhibition of lymphocyte activity and raise the level of T-lymphocyte subpopulations to improve immune function.

Methods

Source of cases

Forty-seven of the patients admitted for treatment in our hospital had case histories that conformed with the criteria for inclusion in the study and were randomly allocated either to the integrated treatment group (24 cases) or the group treated with Western medicine (23 cases). The general characteristics of the 47 patients upon inclusion into the treatment groups are shown in Table 1 and the main symptoms are shown in Fig. 1.

Table 1. Characteristics of 47 patients upon inclusion into one of the two treatment groups

 

Control group
(Western medicine only)

Experiment group
(integrated TCM plus Western medicine)

Total

Number of patients

23

24

47

Sex

     
 

Male

18

14

32

 

Female

5

10

15

Age (years)

     
 

18-20

2

3

5

 

21-30

7

11

18

 

31-40

9

6

15

 

41-50

2

3

5

 

51-60

2

1

3

 

61-65

1

0

1

Profession

     
 

Medical personnel

10

9

19

 

Others

13

15

28

Days after onset at time of inclusion in treatment group

     
 

< 7 days

5

8

13

 

8-14 days

6

5

11

 

> 15 days

12

11

23

Body temperature (°C)

     
 

38.1-39.0

12

13

25

 

39.1-40.0

6

5

11

 

37.1-38.0

3

6

9

 

> 40.0

2

0

2


Fig. 1. Main symptoms of 47 cases at the time of their admission to hospital

Methylprednisolone was administered to patients in both treatment groups and the average cumulative dose was 5278.33 ± 4032.20 mg in the integrated treatment group and 6266.70 ± 4137.25 mg in the group treated with Western medicine. A t-test (p = 0.4113) showed that there was no significant difference between the two groups (p > 0.05) and no significant differences were seen between the two groups with respect to sex, age, course of illness, diagnostic classification and use of hormone.

Diagnostic criteria

The diagnostic criteria used conformed to the Clinical diagnosis criteria for infectious SARS (proposed) issued by the Ministry of Health of the People’s Republic of China on 3 May 2003. The disease severity of forty-seven patients was classified as follows: 44 normal cases (23 in the integrated treatment group); three serious cases (one in the integrated treatment group) and no very serious cases.

Case inclusion criteria

Patients were eligible for inclusion in the study if they had symptoms that conformed with the criteria for the diagnosis of SARS and were aged between 18 and 65 years. The severity of SARS was classified as normal, serious and very serious (according to the criteria in the Guide to clinic work of severe acute respiratory syndrome issued by the Beijing Treatment and Command Centre on 27 April 2003).

Case exclusion criteria

Patients who were not eligible to participate in this study included those suffering from severe cardiovascular and cerebrovascular diseases, liver and kidney diseases, blood diseases, endocrine diseases, pulmonary diseases, neuropsychosis or serious diseases such as tumours or acquired immunodeficiency syndrome (AIDS) that affected the quality of life.

Allocation to treatment groups

A block random method was adopted. The block length was set to 4 which was divided into 15 blocks. The SAS 6.12 software kit was utilized to generate 60 random numbers. Patients were randomly allocated either to the experiment group (TCM plus Western medicine) or to the control group (Western medicine only) according to their serial number.

Clinical therapeutics

Treatment with Western medicine

The Western medicine regimen adopted was that recommended by the Ministry of Health of the People’s Republic of China on 3 May 2003. The basic components of treatment were antiviral agent, antibiotic, immunopotentiator and hormone.

Treatment with integrated traditional Chinese medicine and Western medicine

Integrated therapy with integrated Traditional Chinese medicine and Western medicine was based on the Western medicine regimen described above in combination with the TCM therapy specific to the different types and stages of disease.

Normal cases

Patients with normal SARS received a mixture of honeysuckle flower and isatis leaf prepared with Flos Lonicerae (20 g), Folium Isalipis (20 g), Radix Purariae (15 g) and Folium Perilla (12 g) used to remove heat and ventilate the lung, and regulate channels, and also to remove damp heat and expel pathogens.

Serious and very serious cases

Patients with serious and very serious SARS received a compound mixture of Cordate Houttuynia prepared with Herba Houttuyniae (45 g), Radix Scutellariae (15 g), Semen Armeniacae Amarum (15 g), Radix Bupleuri (15 g), Fossilia Chitonis (30 g) and Radix Pseudostellariae (20 g) to ventilate the lung and subdue adversity, regulate shaoyang, replenish qi and nourish yin.

Recovery stage

Patients at the stage of recovery from disease (reduced dose of hormone) received a mixture of licorice and astragalus root consisting of Radix Astragali Seu Hedysari (45 g), Radix Glycyrrhizae (30 g) and Semen Persicae (30 g) to replenish qi and nourish yin, tonify lung and promote digestion, remove damp heat and regulate channels.

Changes in the ingredients in the above three prescriptions, when used in clinical treatment, were made according to the patient’s actual symptoms. Treatment was with one freshly prepared dose per day decocted and taken orally.

No. 1 SARS granules consisting of Rhizome Cyrtomium (20 g), Radix Bupleuri (10 g), fibrous root of American Ginseng (5 g), Fructus Schisandrae (10 g) was used to remove heat and toxin, replenish qi and nourish yin, and also used against dominance of pathogenic heat and deficiency of both qi and yin.

No. 2 SARS granules which contained Chinese globeflower (10 g), Rhizome Cyrtomium (10 g) and Folium Isalidis (10 g) were used to remove heat, toxin and pathogens and were suitable for patients with excess pathogenic heat.

According to the patients symptoms the appropriate prescriptions were administered for a 3-week treatment course.

Evaluation indices

The evaluation indices included peripheral lymphocytes and T-lymphocyte subpopulations, CD3, CD4/CD8. The normal range of the absolute value of lymphocytes in the peripheral blood was 1.3-3.0 × 109/l, the normal range for CD3 was 66.1-77% and for CD4/CD8, the range of normal values was 0.98- 1.94%.

Observations

Patients were observed for clinical symptoms and changes in peripheral blood lymphocytes and T-lymphocyte subpopulations before and after treatment. Peripheral blood lymphocytes were counted before and after treatment, followed by classification of T-lymphocyte subpopulations into CD3, CD4/CD8. Peripheral blood lymphocytes were counted with a fully automatic blood cell analyser; CD3, CD4/CD8 T-lymphocyte subpopulations were analysed using a laser induced fluorescence technique and flow cytometry. The observation cycle lasted for 3 weeks.

Quality control

To ensure the appropriate quality of this research and to avoid errors in gathering information, the following measures were taken to strengthen quality control during research. The head of the subject group and a coordinator were specifically appointed to coordinate the strategy for data collection in the hospital under the guidance of the official in charge of the centre. Centralized training was provided to the physicians participating in the clinical research so that they all understood and had mastered the treatment proposals and the requirements and precautions for filling out case report forms. They were also instructed in standardization of data gathering; data management and counterchecking of original documents. All herbal pieces used conformed to the criteria of the Chinese Pharmacopoeia (2000 Edition, Volume I) and the patent medicines were all prescription medicines approved by the state administration and available commercially.

Data management and statistical treatment

The authorized physician filled in details of the state of illness and treatment measures in the case report form promptly. After they had been checked and certified as being true and correct by physicians at a higher level, data were entered into the database, then examined and errors in the database were corrected. The database was made read-only for statistical analysis. The database was established using ACCESS, and statistical analysis using t-test and Fisher’s exact test was performed. Measurement data were expressed as mean value ± standard deviation.

Results

Measurement of the absolute value of peripheral blood lymphocytes

The changes in the overall concentrations of peripheral blood lymphocytes in patients before and after treatment are summarized in Table 2. The first measurement of the absolute value of peripheral blood lymphocytes was made at the time of the patient’s admission to the hospital. The mean value was 1.00 ± 0.46 ×109/l in the integrated treatment group and 1.30 ± 0.58 × 109/l in the group treated with Western medicine. The levels in both groups were below normal. No significant difference was found between the two groups (p > 0.05). The mean values in the two treatment groups generally returned to normal after treatment and significant differences were observed when compared with the levels measured before treatment (p < 0.01), which demonstrated the curative effects of the therapy adopted for both treatment groups. However, the difference between the two groups before and after treatment was highly significant (p < 0.01), showing that the integrated therapy with TCM and Western medicine was superior to that with Western medicine alone in raising the level of blood lymphocytes.

Table 2. Changes in concentrations of blood lymphocytes (× 109/l) in patients of both groups before and after treatment

Treatment group

No of cases

Before treatment
(mean ± SD)

After treatment
(mean ± SD)

Difference
(mean ± SD)

Integrated (TCM plus Western medicine)

24

1.00 ± 0.46

1.92 ± 0.74*

0.92 ± 0.61

Western medicine only

23

1.30 ± 0.58

1.80 ± 0.51*

0.49 ± 0.40

p - value

 

0.0616

0.5044

0.0068

 

SD, Standard deviation; TCM, Traditional Chinese medicine
*p <0.01, compared with values in the same group before treatment


The change in absolute value before and after treatment in patients of both groups who had abnormal levels of peripheral blood lymphocytes before treatment is summarized in Table 3.

There were 35 patients with an extremely low absolute level of blood lymphocytes among the 47 cases included in the study. Twenty of these patients were in the integrated treatment group and 15 in the group treated with Western medicine. The mean value at the time when the patients were first included in the treatment groups was 0.85 ± 0.22 ×109/l in the integrated treatment group, and 0.97 ± 0.30 × 109/l in the group treated with Western medicine. No significant difference was seen between the two treatment groups (p > 0.05). After treatment with the different therapeutic regimens there were still 10 patients with abnormal lymphocyte counts; five in each group. Both therapeutic regimens had obvious curative effects and there was a significant difference when the results obtained after treatment were compared with those before treatment (p < 0.01). Comparison before and after treatment of patients from the two groups who had had abnormal blood lymphocyte counts before treatment revealed significant differences (p < 0.05). This comparison showed that integrated therapy with TCM and Western medicine was superior to that of Western medicine alone in restoring blood lymphocyte counts to normal.

Table 3. Changes in concentrations of blood lymphocytes (×109/l) before and after treatment in patients who had abnormal blood lymphocyte counts before treatment

Treatment group

No of cases

Before treatment
(mean ± SD)

After treatment
(mean ± SD)

Difference
(mean ± SD)

Integrated treatment

20

0.85 ± 0.22

1.83 ± 0.71*
(5)a

0.98 ± 0.65

Western medicine only

15

0.97 ± 0.30

1.61 ± 0.41*

0.59 ± 0.34

p - value

 

0.1953

0.3111

0.0332

 

SD, Standard deviation

a The value in parentheses was the number of patients who still had an abnormal blood lymphocyte count after treatment.

* p < 0.01, as compared with values in the same group before treatment


Measurement of blood T-lymphocyte subpopulations CD3, CD4/CD8

Table 4 shows the changes in T-lymphocyte subpopulations before and after treatment.

Table 4. Changes before and after treatment in patients who had abnormal subpopulations of CD3, CD4/CD8 before treatment

Treatment group

Item measured

Before treatment
(%)
(mean ± SD)

After treatment
(%)
(mean ± SD)

Normal range
(%)
(mean ± SD)

Integrated treatment
(TCM plus Western medicine)

CD3

55.56 ± 7.70
(9)a

69.44 ± 6.19
(2)a

66.1 - 77.0

Western medicine only

CD4/CD8

0.80 ± 0.11
(15)a

1.26 ± 0.36
(5)a

0.98 - 1.94

 

CD3

53.80 ± 10.00
(10)a

63.2 ± 8.04
(8)a

66.1 - 77

 

CD4/CD8

0.70 ± 0.16 a

0.97 ± 0.20 a

0.98 - 1.94

 

TCM, Traditional Chinese medicine; SD, standard deviation
a The numbers in parentheses are the numbers of patients with abnormal lymphocyte subpopulations


In total, 38 patients were tested for the classification of their T-lymphocyte subpopulations; 18 were in the integrated treatment group, and 20 in the group treated with Western medicine. Nineteen patients had extremely low CD3 levels before treatment (nine cases in the integrated treatment group and 10 in the group treated with Western medicine). After treatment, two patients in the integrated treatment group had levels that were below normal, yet the overall mean value had returned to within the normal range. In the group treated with Western medicine, the levels in eight patients had still not returned to normal and the overall mean value was below the normal range. In total there were 28 patients with extremely low CD4/CD8 levels before treatment; 15 and 13 patients in the integrated treatment group and the group treated with Western medicine, respectively. The numbers of cases whose levels had normalized after treatment were 10 in the integrated treatment group and three in the group treated with Western medicine, and the overall mean value for patients in the integrated treatment group had normalized, but that of the group treated with Western medicine was still below normal.

Comparison of curative effects of both therapies in restoring the levels of T-lymphocyte subpopulations

The effects of the two treatment regimens on the T-lymphocyte subpopulations are summarized in Table 5.

Table 5. Curative effects of the two therapeutic regimens in restoring the level of T-lymphocyte subpopulations

Treatment group

Number of cases

 

CD3

CD4/CD8

 

Normal

Abnormal

Total

p-value

Normal

Abnormal

Total

p-value

Integrated treatment (TCM plus Western medicine)

7

2

9

0.023

10

5

15

0.030

Western medicine alone

2

8

10

 

3

10

13

 

Total

9

10

19

 

13

15

28

 

 

TCM, Traditional Chinese medicine


Of the nine patients in the integrated treatment group and 10 patients in the group treated with Western medicine who had an extremely low CD3 level before treatment, there were seven and two patients in the two groups, respectively whose levels had normalized after treatment. Of the 15 patients in the integrated treatment group and 13 patients in the group treated with Western medicine alone in whom the CD4/CD8 subpopulation was extremely low before treatment, there were 10 cases in the former group and three in the latter group, respectively, in whom the levels had normalized after treatment. Treatment with integrated TCM and Western medicine was more effective than Western medicine alone in restoring T-lymphocyte subpopulations; the p-values were 0.023 and 0.03, respectively (Fisher’s exact test). Both p-values were less than 0.05, showing that there was a significant difference between the two therapeutic regimens. Therefore, the treatment with integrated Traditional Chinese medicine and Western medicine was significantly superior to treatment with Western medicine alone in restoring normal levels of T-lymphocyte subpopulations.

Discussion and conclusion

SARS is a new disease in humans and a continuing endeavour is being made by medical professionals to achieve a thorough understanding of it. The current treatment for SARS includes an antiviral agent such as ribavirin or oseltamivir; hormone to inhibit damage to the lung and allay the fever; and antibiotics to prevent potential bacterial infections. Treatment with TCM is based on 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 and relevant treatment based on specific symptoms.

It is known that the SARS virus may cause serious infection in the lower respiratory tract and damage to multiple systems in the patient’s body. Clinical workers from mainland China, Hong Kong SAR and other countries have noted that a decrease in absolute value of lymphocytes occurred in most SARS patients, and an effect on T-lymphocyte subpopulations was demonstrated by a decrease in CD3, CD4, CD8 as well as CD4/CD8 (2-5) which shows that damage to the patient’s cellular immune system leads to decreased immune function during the onset and progress of the disease, as demonstrated by the results of this study. Therefore, improving patient’s immune function is critical to the success of treatment.

TCM has accumulated rich clinical experience and rational knowledge relating to the treatment of acute virus infectious diseases. The outbreak of SARS in the winter and spring was due to seasonal epidemic wind-heat pathogens; the disease was highly infectious and characterized by abrupt onset and rapid pathogenic progress, showing the feature of “migratory and variable pathogenic wind”. The main symptoms include fever, myalgia, chest distress and cough. Patients with severe illness may suffer from dyspnoea and cyanotic lips caused by asthma; depletion of yin and yang may occur at the end and the patient may die. Therefore, SARS fits into the category of epidemic febrile diseases with the characteristics of epidemic diseases and epidemic lung diseases. In treating SARS patients with integrated therapeutic regimens of TCM and Western medicine, treatments were prepared based on the integrative concept and the theory of overall analysis of symptoms and signs, the cause, nature and location of the illness and the patient’s physical condition in TCM. The therapy can significantly improve the recovery of patients from illness when used to supplement treatment with Western medicine (2). The data from this study show that the integrated therapy with TCM and Western medicine is superior to treatment with Western medicine alone in promoting the restoration of blood lymphocytes to normal concentrations and raising the level of T-lymphocytes provided that there is no significant difference in the average cumulative dose of hormone between the two groups.

Many herbal medicines such as Radix Astragali Seu Hedysari and Radix Panacis Quinquefolii can help regulate the immune system. This finding reflects the overall therapeutic concept of TCM which is to adjust yin and yang so as to achieve an equilibrium of the two, and to strengthen the body’s resistance and eliminate pathogens so that the patient recovers. In the present study, we found that treatment with integrated TCM and Western medicine can alleviate reduction of lymphocyte activity, raise the levels of T-lymphocyte subpopulations and strengthen the body’s immunity which would further speed up patients’ recovery from illness.

Acknowledgements

Thanks are due to the State Ministry of Science and Technology and State Administration of Traditional Chinese Medicine for providing funding during the campaign against SARS and support for our research work. Thanks are also due to the China Institute of Traditional Chinese Medicine which provided us with training and guidance regarding our study to ensure the high quality of the research, and to the leaders in our hospital and the Institute of Infectious Diseases who also gave us their help.

References

1. Coronavirus never before seen in human is the cause of SARS. 16 April 2003. Available on the Internet at http://www.who.int/csr/sarsarchive/2003-04-16/en/

2. Zou Jinpan, et al. Clinical characteristics of 42 cases of SARS patients and integrated therapeutics of TCM and WM. China Integrated Therapeutics of TCM and WM Magazine, 2003, 23:486-488.

3. Lee N, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. New England Journal of Medicine, 2003, 348:1986-1994.

4. Booth CM, et al. Clinical features and short-term outcomes of 144 patients with SARS in the Greater Toronto Area. Journal of the American Medical Association, 2003, 289:1-9.

5. Zhao Jingmin. Analysis of SARS patient’s suffering from lymphocytes and lymphocyte subpopulations in lungs and kidneys. People’s Liberation Army Medical Journal, 2003, 28:569-571.

 

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