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Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease
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Journal of Traditional Chinese Medical Sciences (2017) xx, 1e7
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.elsevier.com/locate/jtcms
Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease Ka-Kit Chua a,b, Min Li a,b,* a
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, Hong Kong Baptist University, Hong Kong
b
Received 20 May 2016; received in revised form 8 March 2017; accepted 10 March 2017
Available online - - -
KEYWORDS Parkinson disease; Traditional Chinese medicine; Deficiency of spleen qi; Occurrence rate
Abstract Objective: To investigate the frequency of deficiency of spleen qi (DSQ) in persons with Parkinson disease (PD) as well as the correlation between DSQ and PD. Methods: This study comprised three parts: determining the frequency of DSQ in participants with PD; comparing the frequency of DSQ in PD and non-PD participants; and monitoring DSQ in participants with PD for 24 weeks. Outcome measurements were a modified DSQ scale and the Chinese version of the Parkinson Disease Questionnaire 39 (C-PDQ39). Results: A total of 187 participants with PD (mean ages 69.9 9.6 years) completed the assessment in Part 1. Of these, 170 (90.9%) were diagnosed as having DSQ. Thirty non-PD participants (mean ages 66.6 10.2 years) completed the assessment in Part 2. Of these 11 (36.7%) were diagnosed as having DSQ. Positive correlations between total DSQ score and Hoehn-and-Yahr (H&Y) stage (correlation 0.316; P < .001), as well as between DSQ and total C-PDQ39 score (correlation 0.572; P < .001), were observed. For Part 3, 47 participants from Part 1 were observed for 24 weeks. Variation in DSQ symptoms was noted, but all participants developed DSQ by the end of the study. Conclusions: DSQ is 2.5 times higher in PD participants than in the non-PD participants. More PD participants had DSQ in the advanced H&Y stages. A larger study is needed to validate these results on the prevalence of DSQ in persons with PD. ª 2017 Beijing University of Chinese Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
* Corresponding author. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. Fax: þ852 3411 2461. E-mail address: [email protected] (M. Li). Peer review under responsibility of Beijing University of Chinese Medicine. http://dx.doi.org/10.1016/j.jtcms.2017.03.002 2095-7548/ª 2017 Beijing University of Chinese Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Introduction
Participants
Parkinson disease (PD) is one of the most common neurodegenerative diseases.1 The incidence rate of PD is around 37.55 to 61.21 in people over 40.2 It increases sharply with age.3 PD appears to be more common in men than in women at a 3:2 ratio.4,5 In traditional Chinese medicine (TCM), although there is no word that precisely corresponds to the biomedical (Western) term of PD, there are references to a syndrome that is similar.6 PD-like signs and symptoms were first described in Yellow Emperor’s Internal Classic, written during the later Han dynasty. In 1991, “senile shaking syndrome” was validated by “Senile Encephalopathy Seminar by China Association of Chinese Medicine” as the term to be used in TCM that corresponds to PD.7 In biomedicine (Western medicine), PD symptoms are of two types: motor (MS) and non-motor (NMS),8 and persons with PD are further divided into subtypes based on MS or NMS.9 In TCM, as found in our previous study, it is difficult to assign persons with PD to subtypes as it is a complex disease with a combination syndrome pattern of deficiency of origin and excess of superficiality.10 Nevertheless, the main constitution can still be classified based on the major signs and symptoms.11,12 According to TCM theory, the symptoms of fatigue, constipation, and/or mood disorder correlate with the syndrome pattern of deficiency of spleen qi (DSQ). As most persons with PD have these symptoms,13 DSQ appears to be common in the PD population. DSQ is a pattern not restricted to PD and may represent the progression of disease. Hence, treating DSQ may be a potential research and therapeutic direction for PD both in TCM and biomedicine. In our pilot clinical trial, some NMS-type PD patients experienced symptom improvement by using a TCM herbal formula for DSQ.14 While DSQ is likely a major pattern in PD,14 there are currently no published research on PD-related DSQ.15 Therefore, in our study we analyzed the frequency of DSQ in persons with and without PD as the first step toward establishing a relationship between DSQ and PD.
General inclusion criteria were that participants agreed to be examined and interviewed. Specific criteria for Part 1: Adults who were older than 18; had been diagnosed with PD by a licensed biomedical physician; met the criteria of United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria (UKPDBB);16,17 and met the Hoehn and Yahr (H&Y) criteria for stages 1 through 5. Specific criteria for Part 2: Adults who were 50 years or older without a diagnosis of PD. Specific criteria for Part 3: Adults who were older than 18 and had completed the assessment in Part 1. General exclusion criteria were those who had other neurologic diseases, i.e., dementia; had another lifethreatening disease(s), such as acute cardiovascular diseases, pneumonia, cancer; had non-chronic disease(s), such as acute respiratory infection, acute gastroenteritis, acute bone fracture; or had participated in an interventional clinical trial within 30 days of the assessment. Specific exclusion criteria for Part 1 were those who had a typical or drug-induced parkinsonism and who were pregnant or breastfeeding. For Part 2, the only specific exclusion criterion was a diagnosis of parkinsonism.
Method Study design This study was divided into three parts: Part 1) Confirming diagnosis of PD: Persons with parkinsonism were recruited, examined, and interviewed to validate their diagnosis of PD and presence of DSQ. Part 2) Controlling: To control the possibility of DSQ being present simply due to aging, older adults without PD were interviewed to determine their prevalence of DSQ. This group served as the control group. Since PD seldom develops in people under the age of 50, only non-PD persons older than 50 were recruited. Part 3) Monitoring: After confirmation of PD, persons who were willing to participate in further study underwent an additional 24 weeks’ observation to monitor any changes in DSQ pattern. No additional active intervention was applied, but they were instructed to continue their routine medications.
Settings and locations Parts 1 and 3 were carried out at the Hong Kong Baptist University Chinese Medicine Specialty Centre, which is a Chinese medicine clinic managed by the School of Chinese Medicine of Hong Kong Baptist University. Part 2 was carried at public parks in Hong Kong including Eastern district, Yau Tsim Mong District, and Sai Kung District.
Recruitment procedures All participants in all three parts were assessed by the first author (KK Chua), a licensed Chinese medicine practitioner in Hong Kong. The objective, procedures, and nature of the study were explained to each participant. Verbal consent was obtained from each participant and caregiver (if applicable) before the assessment. They were informed that they could withdraw from the study freely at any time during the assessment. For Part 1, two methods were used to recruit participants with PD: advertisements in local newspapers and referral from Chinese medicine clinics of Hong Kong Baptist University. For Part 2, non-PD persons were recruited randomly in public parks. For Part 3, participants who had completed the Part 1 assessment were invited to return for a 24-week observation period. Part 3 was started after the completion of Part 1.
Questionnaires Criteria for diagnosing DSQ were extracted from Guiding Principles for Clinical Research on New Drugs of Traditional Chinese Medicine.18 It includes 4 primary symptoms and 13 secondary symptoms. Based on these criteria, the original
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Spleen qi deficiency in Parkinson disease grading system (none, mild, moderate, and severe) was modified into a scoring scale of 0e3 (Supplementary Table 1).
Outcome measurement and its assessment Primary outcome was comparing the frequency of DSQ in participants with PD to the frequency of DSQ in non-PD participants. Total score of DSQ, total score, and domain score of the Chinese version of the Parkinson Disease Questionnaire 39 (C-PDQ39)19,20 were also analyzed for the PD group. Both DSQ and C-PDQ39 were completed by the assessor in conversation with the subjects. For Parts 1 and 2, outcome measurements were carried out on the same day as the visits. It was suggested to PD participants that they should be assessed in the “on” state to minimize any unwanted bias due to mood. For Part 3, outcome measurements were conducted once every 8 weeks to the end of the study. Assessments were rescheduled within 7 days after the scheduled visit if there were unexpected conditions, such as severe weather, that prevented meeting. All participants received phone call reminders one day before the examination. A special email account ([email protected]) and direct telephone line (þ852 6700 8538) were created for communication with participants.
Statistical analysis Double data entry method was used to ensure the quality of data. The raw data of this study can be found in Supplementary Table 2. For group sample sizes larger than 30, analysis was done by independent sample t test or chi-square test as appropriate. For group sizes smaller than 30, the ManneWhitney U test was used. The first step of the analysis was determining the DSQ frequency of the PD group in Part 1 and non-PD group in Part 2. Then, DSQ total score and sub-scores of the PD group in Part 1 were compared to the non-PD group in Part 2. With regard to the PD participants of Part 1, the C-PDQ39 and PD severity of those with and without DSQ were compared. With regard to data collected in Part 3, differences in the C-PDQ-39 total score between each assessment point and baseline were compared for PD participants with and without DSQ. The number of PD participants with DSQ was calculated at each assessment point to determine if there was any variation from the baseline. Since there was no intervention in the study, participants for whom we had no data were excluded from related parts of the analysis. Analyses were done with the IBM SPSS Statistics 19.0 package (IBM, Armonk, NY).
3 the study (Fig. 1). Of these individuals, 187 (115 male; 72 female; mean age 69.9 9.6 years; mean duration of PD 5.3 5.2 years; H&Y stage 1.94 0.84) completed the survey for Part 1. Twenty-nine individuals were excluded from the study due to questionable parkinsonism. For Part 2, 31 participants without parkinsonism agreed to be interviewed, of which 30 individuals (9 male; 21 female; mean age 66.6 10.2 years) completed the questionnaire.
Comparison of DSQ in PD and non-PD participants Of the 187 participants with PD in Part 1, 170 (90.9%) were diagnosed as having DSQ. Of the 30 non-PD participants in Part 2, 11 (36.7%) were diagnosed as having DSQ. The occurrence rate of DSQ in PD participants was significantly higher than in non-PD participants (P < .001, Table 1). However, there was a significant difference in the sex ratio of the two groups (P Z .006). That is, in the PD participants with DSQ, the male to female ratio was 1.54:1, while in the non-PD with DSQ group the ratio was 1:4.5. Further analysis revealed that, with regard to total DSQ scores (P < .001) and sub-scores on Questions 6, 10, 11 and 13, PD participants with DSQ consistently scored much higher than nonPD participants with DSQ (Table 1).
Comparison of PD characteristics in DSQ and nonDSQ PD participants PD participants with and without DSQ showed no significant differences in terms of general characteristics (Table 2). However, total C-PDQ39 scores and all domain scores of PD participants with DSQ were significantly higher than those of PD participants without DSQ. Significant difference in the H&Y stage was also noted between the two groups.
Correlation between DSQ and PD conditions Basic information of PD participants in Part 1 based on their H&Y stage was tabulated (Table 3). A positive correlation between the total DSQ score and the H&Y stage (correlation 0.316; P < .001) was observed. The more advanced their H&Y stage, the more likely they were to have DSQ. Furthermore, there were positive correlations between total DSQ score and total C-PDQ39 score (correlation 0.572; P < .001) as well as total DSQ score and age (correlation 0.235; P Z .001). However, there were no correlations between total DSQ score and disease duration (correlation 0.060; P Z .414) nor between total DSQ score and daily Ldopa dosage (correlation 0.102; P Z .163). In addition, no correlation was observed in the non-PD participants between total DSQ score and age (correlation 0.026; P Z .892) in Part 2.
Monitoring of PD parameters
Results Recruitment and questionnaire completion From September 1, 2011 to November 30, 2011, 216 persons with parkinsonism agreed to be interviewed for eligibility in
Baseline characteristics of Part 3 were analyzed (Table 4). Forty-seven participants (33 male; 14 female; mean ages 62.0 8.0 years; mean duration of PD 5.2 3.9 years; H&Y stage 2.00 0.55) from Part 1 agreed to continue the assessment and were enrolled in Part 3. Forty-four participants were diagnosed with DSQ and 3participants were
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Figure 1
Study flowchart.
diagnosed as non-DSQ at the baseline. Six participants dropped out during the monitoring period for personal reasons. Thirty-eight participants in the DSQ group and 3 in the non-DSQ group completed Part 3 (Fig. 1, Table 5).
Variation in DSQ parameters Throughout the 24 weeks’ observation period, variation in DSQ parameters was noted in both groups. In the DSQ group, the parameters remained unchanged in most of the participants throughout the 24 weeks, while DSQ in a small number of participants improved temporarily. In the nonDSQ group, all participants developed DSQ by the end of the observation period.
Variation in the C-PDQ39 Changes in the total C-PDQ39 score were observed throughout the 24 weeks’ observation period (Table 6). There was a steady worsening trend in PD as suggested by a rise in the total C-PDQ39 score of in the DSQ group. However, a temporary improvement in PD symptoms was observed as reflected by the drop in the total C-PDQ39 score in the non-DSQ group. Although there was a significant difference in total C-PDQ39 scores for the DSQ and
non-DSQ groups at week 16, this was not the case for the scores at weeks 8 and 24.
Discussion In Parts 1 and 2, although DSQ was present in non-PD participants, the frequency of DSQ was 2.5 times higher in PD participants. In addition, DSQ in PD participants was in general more severe than in non-PD participants. There was a close positive correlation between H&Y stage and DSQ, as well as between total C-PDQ39 score and DSQ. Age also showed positive correlation with DSQ in PD participants, while similar correlation was not observed in non-PD participants. Since PD is a slow progressive disease, it is reasonable that older PD participants showed more severe PD symptoms. The correlation between age and DSQ in PD participants may be due to correlation of PD with age. For Part 3, there was variation in the presence of DSQ, parameters suggesting that DSQ is reversible. However, in this study most participants with PD eventually developed symptoms of DSQ. Based on results in Part 1, non-DSQ PD participants should have lower total C-PDQ39 scores than DSQ PD participants. The fluctuation of C-PDQ39 in the nonDSQ PD group could be related to the small sample size (n Z 3 only). In this case, even a small change in a single
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Spleen qi deficiency in Parkinson disease
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Table 1 Comparison of DSQ between PD and non-PD participants in Parts 1 and 2.a Parameter
PD group (n Z 187)
Non-PD group (n Z 30)
P
Participants with DSQ (%) Sex: M (%) F (%) Age Total DSQ score Q1-dyspepsia Q2-fatigue Q3-abdominal distention Q4-abnormal defecation Q5-listlessness Q6-dysgeusia Q7-abdominal pain Q8-nausea Q9-gastric discomfort Q10-gurgling sound Q11-sallow complexion Q12-edema Q13-weakness to defecate
170 (90.9) 103 (89.6) 67 (93.1) 65 15 85 01 11 00 00 11 01 00 00 00 01 11 01 23
11 (36.7) 2 (22.2) 9 (42.9) 64 12 43 01 10 00 00 10 00 00 00 01 00 11 00 00
>.001b .006b .828c >.001c .756c .219c .812c .162c .138c .019c .449c .663c .322c .034c .012c .157c >.001c
Abbreviations: DSQ: deficiency of spleen qi; PD: Parkinson disease. a Data are expressed as median interquartile range (IQR). b PD group with DSQ compared with non-PD group with DSQ by Chi-square test. c PD group with DSQ compared with non-PD group with DSQ by ManneWhitney U test.
Table 2
subject would induce a great variation in the statistical results. In general, results of Part 3 indicate that PD symptoms may vary over time in PD individuals with DSQ, but remain relatively stable in PD individuals without DSQ. In Part 1, we observed a drop in daily L-dopa intake in PD participants with H&Y stage 4 despite the fact their disease duration was the longest. This may be due to complications of advanced PD, such as dyskinesia. Hence, L-dopa daily intake and duration as well as PD duration might not be positively correlated with DSQ because all PD participants exhibited DSQ in the advanced H&Y stages. On the other hand, the percentage of PD participants with DSQ was positively correlated with the H&Y stage and total C-PDQ39 score. The baseline medical histories of PD participants with and without DSQ in Part 1 were very similar. There was only a small proportion of participants with advanced H&Y stages. Thus, the progression of PD might be regulated by treating DSQ as it is closely related to the general condition of PD. In TCM, the term “spleen” refers to the energy pathway that controls the production of blood and vital energy (qi), which corresponds to the digestive system in biomedicine. From the results in Part 1, PD participants with DSQ presented with dysgeusia (DSQ-Q6), sallow complexion (DSQQ11), and weakness to defecate (DSQ-13). Hence, we recommend that TCM treatment of DSQ in persons with PD should focus on these symptoms. This study has limitations. The sample sizes in all three parts were small. Although the total number of subjects included in each part was larger than 30, each subgroup numbered less than 30. Small numerical variation within a subgroup may cause large statistical variation in the analysis. In fact, it was hard to determine the appropriate sample size at the beginning of the study because there was no previous research data or information on DSQ frequency, neither for persons with PD nor without PD. This research
Comparison between DSQ and non-DSQ PD participants in Part 1.a
Parameter
PD with DSQ (n Z 170)
PD without DSQ (n Z 17)
P
Sex, M/F Age, y H&Y stages Disease duration, y L-dopa duration, y L-dopa dosage, mg/d C-PDQ39 Total Score D1-mobility D2-activities of daily living D3-emotional well-being D4-stigma D5-social support D6-cognitions D7-communication D8-bodily discomfort
103/67 65.0 15 2.00 1 4.0 5.0 2.0 4.5 300.00 350.00 45.50 37 16.00 16 7.00 9 5.00 8 4.50 5 1.00 3 5.00 4 2.00 3 4.00 4
12/5 65.0 15 2.00 1 3.0 4.0 1.0 3.5 300.00 350.00 14 30 4.00 7 2.00 6 2.00 3 2.00 5 0.00 0 2.00 3 0.00 2 1.00 3
.419b .828c .043c .347c .133c .234c >.001c >.001c .001c >.001c .016c .009c .001c .001c >.001c
Abbreviations: C-PDQ39: Chinese version of the Parkinson Disease Questionnaire 39; DSQ: deficiency of spleen qi; H&Y: Hoehn and Yahr; PD: Parkinson disease. a Data are expressed as median interquartile range (IQR). b PD group with DSQ compared with PD group without DSQ by Chi-square test. c PD group with DSQ compared with PD group without DSQ by ManneWhitney U test.
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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K.-K. Chua, M. Li Table 3
Basic information based on H&Y stages in Part 1 PD participants.a
Parameter
H&Y 1 (n Z 60)
H&Y 2 (n Z 92)
H&Y 3 (n Z 23)
H&Y 4 (n Z 12)
Sex, M/F Age, y Disease duration, y L-dopa duration, y L-dopa dosage, mg/d Number of DSQ (%) Total DSQ score Total C-PDQ39 score
40/20 61.3 (9.7) 3.0 (2.6) 1.8 (2.4) 240.00 (214.48) 52 (86.7) 6.58 (3.19) 33.63 (20.36)
56/36 64.6 (9.4) 5.7 (5.2) 3.9 (4.6) 333.15 (295.23) 83 (90.2) 8.39 (4.33) 46.34 (23.78)
14/9 65.3 (9.4) 7.9 (5.3) 4.8 (4.2) 673.91 (695.58) 23 (100) 10.39 (5.18) 62.04 (20.93)
5/7 69.8 (8.2) 8.7 (9.2) 5.7 (5.2) 529.17 (443.36) 12 (100) 11.08 (4.68) 85.83 (26.35)
Abbreviations: C-PDQ39: Chinese version of the Parkinson Disease Questionnaire 39; DSQ: deficiency of spleen qi; H&Y: Hoehn and Yahr; PD: Parkinson disease. a Data are expressed as mean (SD) except sex ratio.
Table 4
Baseline characteristics of PD participants in Part 3.a
Parameter
PD with DSQ (n Z 44)
PD without DSQ (n Z 3)
P
Sex, M/F Age, y Disease duration, y L-dopa duration, y L-dopa dosage, mg/d H&Y stages DSQ total score C-PDQ39 total score
30/14 62.0 14 4.0 3.8 3.3 4.0 300.00 300 2.00 0.00 5.50 4 18.50 19
3/0 60.0 6.0 2.0 300.0 2.00 2.00 30
.244b .206c .742c .161c .692c .279c .029c .983c
Abbreviations: C-PDQ39: Chinese version of the Parkinson Disease Questionnaire 39; DSQ: deficiency of spleen qi; H&Y: Hoehn and Yahr; PD: Parkinson disease. a Data are expressed as median interquartile range (IQR). b PD group with DSQ compared with PD group without DSQ by Chi-square test. c PD group with DSQ compared with PD group without DSQ by ManneWhitney U test.
Table 5
Week 0 Dropout Week 8 Dropout Week 16 Dropout Week 24 Dropout
Variation in DSQ throughout the 24 weeks in Part 3. DSQ group (Male/Female)
Non-DSQ group (Male/Female)
With DSQ
Without DSQ
With DSQ
0/0
0/0
30/14 0/0 27/11
1/3
1/0
2/0 0/0
2/2
1/0
4/0 24/14
3/0 0/0
2/0 24/12
Without DSQ
2/0 0/0
0/0
3/0
6/0
0/0 0/0
Abbreviation: DSQ: deficiency of spleen qi.
provides important, hitherto missing, basic information on the occurrence rate of DSQ and the possible factors affecting DSQ in PD subjects. The trends revealed in this small study indicate that a larger scale study of DSQ prevalence would be justified and likely be productive.
A second limitation occurred with the sex differences in the PD and non-PD groups with regard to DSQ. As mentioned, males are more likely to have PD than females. Thus, it was reasonable to have more male PD participants in the study. However, for the non-PD groups, many more females were willing to be part of the study than males. Males were not willing to be interviewed for a number of reasons. For example, they assumed they were healthy or they did not want to share personal information with an unknown person. Thus, female participants in both the PD and non-PD groups exhibited higher frequencies of DSQ, which may have impacted the comparison of DSQ occurrence between the sexes. Therefore, a larger scale study on the relationship between DSQ and the sexes is suggested. Yet another limitation of the study was the geographically small sampling area for Part 2. Because the non-PD participants of Part 2 were recruited in a small area, the frequency of DSQ in these non-PD participants might not represent the whole population perfectly. Even so, these individuals were recruited from the entire three regions in Hong Kong, i.e. Eastern District of Hong Kong Island, Yau Tsim Mong District of Kowloon, and Sai Kung District of the New Territories. Thus, the Part 2 sample may still exhibit a trend of DSQ in Hong Kong non-PD participants.
Conclusions More than 90% of persons with PD who participated in this study exhibited DSQ, which was 2.5 times that of non-PD participants. In general, DSQ was more serious in PD than in non-PD participants. Furthermore, in PD participants, there was a positive correlation between severity of DSQ and severity of their PD symptoms. More participants in the advanced H&Y stages of PD had DSQ. Although there was some fluctuation in DSQ parameters over time, all PD participants developed DSQ by the end of the study. These clear trends suggest that DSQ could be helpful both in diagnosis and treatment of PD. Therefore, larger investigations on the prevalence of DSQ in persons with PD are needed to validate our results. Finally, TCM resolves DSQ through a number of modalities, including acupuncture and herbs, and these modalities should be continued to be studied for new, effective therapies for PD.
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Spleen qi deficiency in Parkinson disease Table 6
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Changes in total C-PDQ39 score throughout 24 weeks in Part 3.
Parameter (number of subjects at Week 0)
PD with DSQa (n Z 44)
PD without DSQb (n Z 3)
P
Difference at Week 8 (n) Difference at Week 16 (n) Difference at Week 24 (n)
3.00 14.50 (n Z 42) 4.00 12.25 (n Z 40) 5.50 14.50 (n Z 38)
10.00 (n Z 3) 10.00 (n Z 3) 0.00 (n Z 3)
0.069c 0.047c 0.423c
Values are given as median interquartile range (IQR) (n Z number of subjects at that time point). Values are the score changed within the same group between each time point and baseline (score at measurement point minus score at baseline). c Score changes in PD with DSQ compared with score changes in PD without DSQ at each time point by ManneWhitney U test. a
b
Competing interests The authors declare that they have no competing interests.
Author roles The authors’ contributions are as follows: KK Chua conceived the project and coordinated all efforts in the trial; M Li monitored the trial and contributed to the design of the trial; KK Chua and M Li helped with data analysis, discussion and wrote the paper.
Acknowledgements This work is part of the thesis by Stroke and Clinical Neurosciences (CNS) Master Programme, The Chinese University of Hong Kong (CUHK). It was supported by research grants (SCM/10-11/03, IRMS/12-13/1A) from Hong Kong Baptist University and Mr. & Mrs. Ko Chi Ming Center for Parkinson’s Disease Research. The authors would like to thank Prof. Vincent Mok and Prof. Adrian Wong from CUHK for their technical support as well as Prof. Shu-Leong Ho and Dr. KinLun Tsang for providing the Chinese version of Parkinson’s Disease Questionnaire 39. Also, thanks to Dr. Feng Sun and Ms. Vicky Keng from the Clinical Division, School of Chinese Medicine, HKBU for their great support on this study. The authors would also like to thank Dr. Martha Dahlen for her English editing of this manuscript.
Appendix A. Supplementary data Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.jtcms.2017.03.002.
References 1. Elbaz A, Carcaillon L, Kab S, et al. Epidemiology of Parkinson’s disease. Rev Neurol. 2016;172(1):14e26. 2. Hirsch L, Jette N, Frolkis A, et al. The incidence of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology. 2016;46(4):292e300. 3. Wirdefeldt K, Adami HO, Cole P, et al. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. European journal of epidemiology. 2011;26(suppl 1):S1eS58.
4. Wooten GF, Currie LJ, Bovbjerg VE, et al. Are men at greater risk for Parkinson’s disease than women? Journal of Neurol Neurosurg Psychiatry. 2004;75(4):637e639. 5. Taylor KS, Cook JA, Counsell CE. Heterogeneity in male to female risk for Parkinson’s disease. Journal of Neurol Neurosurg Psychiatry. 2007;78(8):905e906. 6. Li Q, Zhao D, Bezard E. Traditional Chinese medicine for Parkinson’s disease: a review of Chinese literature. Behav Pharmacol. 2006;17(5e6):403e410. 7. CX L. Assessment standard of treatment effect for senile shaking palsy. In: Proc Beijing Chin Med Univ. vol. 15(4). 1992:39e41. 8. Massano J, Bhatia KP. Clinical approach to Parkinson’s disease: features, diagnosis, and principles of management. Cold Spring Harb Perspect Med. 2012;2(6):a008870. 9. Yang H-J, Kim YE, Yun JY, et al. Identifying the clusters within nonmotor manifestations in early Parkinson’s disease by using unsupervised cluster analysis. PLoS One. 2014;9(3):e91906. 10. Li JJ, Chua KK, Li M. Constitutional study of Parkinson’s disease patients based on traditional Chinese medicine pattern differentiation. Integr Med Int. 2014;1(3):170e175. 11. Hua Lu WP, Wang Jun, Wu Chunlan, et al. The current status of integrative therapies in treating Parkinson’s disease in six general hospitals in shanghai. Int J Integr Med. 2013;1(17). 12. Jiang WY. Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science. Trends Pharmacol Sci. 2005;26(11):558e563. 13. Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 2006;5(3):235e245. 14. Kum WF, Durairajan SS, Bian ZX, et al. Treatment of idiopathic Parkinson’s disease with traditional Chinese herbal medicine: a randomized placebo-controlled pilot clinical study. Evid Based Complement Altern Med. 2011;2011:724353. 15. Chung V, Liu L, Bian Z, et al. Efficacy and safety of herbal medicines for idiopathic Parkinson’s disease: a systematic review. Mov Disord. 2006;21(10):1709e1715. 16. Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181e184. 17. Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. Journal of Neurol Neurosurg Psychiatry. 1988;51(6):745e752. 18. XY Z. The Guidance for Clinical Research of New Chinese Herbal Medicine. Beijing: Chinese Medical Scientific Publishers; 2002. 19. Jenkinson C, Fitzpatrick R, Peto V, et al. The Parkinson’s Disease Questionnaire (PDQ-39): development and validation of a Parkinson’s disease summary index score. Age ageing. 1997; 26(5):353e357. 20. Tsang KL, Chi I, Ho SL, et al. Translation and validation of the standard Chinese version of PDQ-39: a quality-of-life measure for patients with Parkinson’s disease. Mov Disord. 2002;17(5): 1036e1040.
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Journal of Traditional Chinese Medical Sciences (2017) xx, 1e7
Available online at www.sciencedirect.com
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Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease Ka-Kit Chua a,b, Min Li a,b,* a
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, Hong Kong Baptist University, Hong Kong
b
Received 20 May 2016; received in revised form 8 March 2017; accepted 10 March 2017
Available online - - -
KEYWORDS Parkinson disease; Traditional Chinese medicine; Deficiency of spleen qi; Occurrence rate
Abstract Objective: To investigate the frequency of deficiency of spleen qi (DSQ) in persons with Parkinson disease (PD) as well as the correlation between DSQ and PD. Methods: This study comprised three parts: determining the frequency of DSQ in participants with PD; comparing the frequency of DSQ in PD and non-PD participants; and monitoring DSQ in participants with PD for 24 weeks. Outcome measurements were a modified DSQ scale and the Chinese version of the Parkinson Disease Questionnaire 39 (C-PDQ39). Results: A total of 187 participants with PD (mean ages 69.9 9.6 years) completed the assessment in Part 1. Of these, 170 (90.9%) were diagnosed as having DSQ. Thirty non-PD participants (mean ages 66.6 10.2 years) completed the assessment in Part 2. Of these 11 (36.7%) were diagnosed as having DSQ. Positive correlations between total DSQ score and Hoehn-and-Yahr (H&Y) stage (correlation 0.316; P < .001), as well as between DSQ and total C-PDQ39 score (correlation 0.572; P < .001), were observed. For Part 3, 47 participants from Part 1 were observed for 24 weeks. Variation in DSQ symptoms was noted, but all participants developed DSQ by the end of the study. Conclusions: DSQ is 2.5 times higher in PD participants than in the non-PD participants. More PD participants had DSQ in the advanced H&Y stages. A larger study is needed to validate these results on the prevalence of DSQ in persons with PD. ª 2017 Beijing University of Chinese Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
* Corresponding author. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. Fax: þ852 3411 2461. E-mail address: [email protected] (M. Li). Peer review under responsibility of Beijing University of Chinese Medicine. http://dx.doi.org/10.1016/j.jtcms.2017.03.002 2095-7548/ª 2017 Beijing University of Chinese Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Introduction
Participants
Parkinson disease (PD) is one of the most common neurodegenerative diseases.1 The incidence rate of PD is around 37.55 to 61.21 in people over 40.2 It increases sharply with age.3 PD appears to be more common in men than in women at a 3:2 ratio.4,5 In traditional Chinese medicine (TCM), although there is no word that precisely corresponds to the biomedical (Western) term of PD, there are references to a syndrome that is similar.6 PD-like signs and symptoms were first described in Yellow Emperor’s Internal Classic, written during the later Han dynasty. In 1991, “senile shaking syndrome” was validated by “Senile Encephalopathy Seminar by China Association of Chinese Medicine” as the term to be used in TCM that corresponds to PD.7 In biomedicine (Western medicine), PD symptoms are of two types: motor (MS) and non-motor (NMS),8 and persons with PD are further divided into subtypes based on MS or NMS.9 In TCM, as found in our previous study, it is difficult to assign persons with PD to subtypes as it is a complex disease with a combination syndrome pattern of deficiency of origin and excess of superficiality.10 Nevertheless, the main constitution can still be classified based on the major signs and symptoms.11,12 According to TCM theory, the symptoms of fatigue, constipation, and/or mood disorder correlate with the syndrome pattern of deficiency of spleen qi (DSQ). As most persons with PD have these symptoms,13 DSQ appears to be common in the PD population. DSQ is a pattern not restricted to PD and may represent the progression of disease. Hence, treating DSQ may be a potential research and therapeutic direction for PD both in TCM and biomedicine. In our pilot clinical trial, some NMS-type PD patients experienced symptom improvement by using a TCM herbal formula for DSQ.14 While DSQ is likely a major pattern in PD,14 there are currently no published research on PD-related DSQ.15 Therefore, in our study we analyzed the frequency of DSQ in persons with and without PD as the first step toward establishing a relationship between DSQ and PD.
General inclusion criteria were that participants agreed to be examined and interviewed. Specific criteria for Part 1: Adults who were older than 18; had been diagnosed with PD by a licensed biomedical physician; met the criteria of United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria (UKPDBB);16,17 and met the Hoehn and Yahr (H&Y) criteria for stages 1 through 5. Specific criteria for Part 2: Adults who were 50 years or older without a diagnosis of PD. Specific criteria for Part 3: Adults who were older than 18 and had completed the assessment in Part 1. General exclusion criteria were those who had other neurologic diseases, i.e., dementia; had another lifethreatening disease(s), such as acute cardiovascular diseases, pneumonia, cancer; had non-chronic disease(s), such as acute respiratory infection, acute gastroenteritis, acute bone fracture; or had participated in an interventional clinical trial within 30 days of the assessment. Specific exclusion criteria for Part 1 were those who had a typical or drug-induced parkinsonism and who were pregnant or breastfeeding. For Part 2, the only specific exclusion criterion was a diagnosis of parkinsonism.
Method Study design This study was divided into three parts: Part 1) Confirming diagnosis of PD: Persons with parkinsonism were recruited, examined, and interviewed to validate their diagnosis of PD and presence of DSQ. Part 2) Controlling: To control the possibility of DSQ being present simply due to aging, older adults without PD were interviewed to determine their prevalence of DSQ. This group served as the control group. Since PD seldom develops in people under the age of 50, only non-PD persons older than 50 were recruited. Part 3) Monitoring: After confirmation of PD, persons who were willing to participate in further study underwent an additional 24 weeks’ observation to monitor any changes in DSQ pattern. No additional active intervention was applied, but they were instructed to continue their routine medications.
Settings and locations Parts 1 and 3 were carried out at the Hong Kong Baptist University Chinese Medicine Specialty Centre, which is a Chinese medicine clinic managed by the School of Chinese Medicine of Hong Kong Baptist University. Part 2 was carried at public parks in Hong Kong including Eastern district, Yau Tsim Mong District, and Sai Kung District.
Recruitment procedures All participants in all three parts were assessed by the first author (KK Chua), a licensed Chinese medicine practitioner in Hong Kong. The objective, procedures, and nature of the study were explained to each participant. Verbal consent was obtained from each participant and caregiver (if applicable) before the assessment. They were informed that they could withdraw from the study freely at any time during the assessment. For Part 1, two methods were used to recruit participants with PD: advertisements in local newspapers and referral from Chinese medicine clinics of Hong Kong Baptist University. For Part 2, non-PD persons were recruited randomly in public parks. For Part 3, participants who had completed the Part 1 assessment were invited to return for a 24-week observation period. Part 3 was started after the completion of Part 1.
Questionnaires Criteria for diagnosing DSQ were extracted from Guiding Principles for Clinical Research on New Drugs of Traditional Chinese Medicine.18 It includes 4 primary symptoms and 13 secondary symptoms. Based on these criteria, the original
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Spleen qi deficiency in Parkinson disease grading system (none, mild, moderate, and severe) was modified into a scoring scale of 0e3 (Supplementary Table 1).
Outcome measurement and its assessment Primary outcome was comparing the frequency of DSQ in participants with PD to the frequency of DSQ in non-PD participants. Total score of DSQ, total score, and domain score of the Chinese version of the Parkinson Disease Questionnaire 39 (C-PDQ39)19,20 were also analyzed for the PD group. Both DSQ and C-PDQ39 were completed by the assessor in conversation with the subjects. For Parts 1 and 2, outcome measurements were carried out on the same day as the visits. It was suggested to PD participants that they should be assessed in the “on” state to minimize any unwanted bias due to mood. For Part 3, outcome measurements were conducted once every 8 weeks to the end of the study. Assessments were rescheduled within 7 days after the scheduled visit if there were unexpected conditions, such as severe weather, that prevented meeting. All participants received phone call reminders one day before the examination. A special email account ([email protected]) and direct telephone line (þ852 6700 8538) were created for communication with participants.
Statistical analysis Double data entry method was used to ensure the quality of data. The raw data of this study can be found in Supplementary Table 2. For group sample sizes larger than 30, analysis was done by independent sample t test or chi-square test as appropriate. For group sizes smaller than 30, the ManneWhitney U test was used. The first step of the analysis was determining the DSQ frequency of the PD group in Part 1 and non-PD group in Part 2. Then, DSQ total score and sub-scores of the PD group in Part 1 were compared to the non-PD group in Part 2. With regard to the PD participants of Part 1, the C-PDQ39 and PD severity of those with and without DSQ were compared. With regard to data collected in Part 3, differences in the C-PDQ-39 total score between each assessment point and baseline were compared for PD participants with and without DSQ. The number of PD participants with DSQ was calculated at each assessment point to determine if there was any variation from the baseline. Since there was no intervention in the study, participants for whom we had no data were excluded from related parts of the analysis. Analyses were done with the IBM SPSS Statistics 19.0 package (IBM, Armonk, NY).
3 the study (Fig. 1). Of these individuals, 187 (115 male; 72 female; mean age 69.9 9.6 years; mean duration of PD 5.3 5.2 years; H&Y stage 1.94 0.84) completed the survey for Part 1. Twenty-nine individuals were excluded from the study due to questionable parkinsonism. For Part 2, 31 participants without parkinsonism agreed to be interviewed, of which 30 individuals (9 male; 21 female; mean age 66.6 10.2 years) completed the questionnaire.
Comparison of DSQ in PD and non-PD participants Of the 187 participants with PD in Part 1, 170 (90.9%) were diagnosed as having DSQ. Of the 30 non-PD participants in Part 2, 11 (36.7%) were diagnosed as having DSQ. The occurrence rate of DSQ in PD participants was significantly higher than in non-PD participants (P < .001, Table 1). However, there was a significant difference in the sex ratio of the two groups (P Z .006). That is, in the PD participants with DSQ, the male to female ratio was 1.54:1, while in the non-PD with DSQ group the ratio was 1:4.5. Further analysis revealed that, with regard to total DSQ scores (P < .001) and sub-scores on Questions 6, 10, 11 and 13, PD participants with DSQ consistently scored much higher than nonPD participants with DSQ (Table 1).
Comparison of PD characteristics in DSQ and nonDSQ PD participants PD participants with and without DSQ showed no significant differences in terms of general characteristics (Table 2). However, total C-PDQ39 scores and all domain scores of PD participants with DSQ were significantly higher than those of PD participants without DSQ. Significant difference in the H&Y stage was also noted between the two groups.
Correlation between DSQ and PD conditions Basic information of PD participants in Part 1 based on their H&Y stage was tabulated (Table 3). A positive correlation between the total DSQ score and the H&Y stage (correlation 0.316; P < .001) was observed. The more advanced their H&Y stage, the more likely they were to have DSQ. Furthermore, there were positive correlations between total DSQ score and total C-PDQ39 score (correlation 0.572; P < .001) as well as total DSQ score and age (correlation 0.235; P Z .001). However, there were no correlations between total DSQ score and disease duration (correlation 0.060; P Z .414) nor between total DSQ score and daily Ldopa dosage (correlation 0.102; P Z .163). In addition, no correlation was observed in the non-PD participants between total DSQ score and age (correlation 0.026; P Z .892) in Part 2.
Monitoring of PD parameters
Results Recruitment and questionnaire completion From September 1, 2011 to November 30, 2011, 216 persons with parkinsonism agreed to be interviewed for eligibility in
Baseline characteristics of Part 3 were analyzed (Table 4). Forty-seven participants (33 male; 14 female; mean ages 62.0 8.0 years; mean duration of PD 5.2 3.9 years; H&Y stage 2.00 0.55) from Part 1 agreed to continue the assessment and were enrolled in Part 3. Forty-four participants were diagnosed with DSQ and 3participants were
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Figure 1
Study flowchart.
diagnosed as non-DSQ at the baseline. Six participants dropped out during the monitoring period for personal reasons. Thirty-eight participants in the DSQ group and 3 in the non-DSQ group completed Part 3 (Fig. 1, Table 5).
Variation in DSQ parameters Throughout the 24 weeks’ observation period, variation in DSQ parameters was noted in both groups. In the DSQ group, the parameters remained unchanged in most of the participants throughout the 24 weeks, while DSQ in a small number of participants improved temporarily. In the nonDSQ group, all participants developed DSQ by the end of the observation period.
Variation in the C-PDQ39 Changes in the total C-PDQ39 score were observed throughout the 24 weeks’ observation period (Table 6). There was a steady worsening trend in PD as suggested by a rise in the total C-PDQ39 score of in the DSQ group. However, a temporary improvement in PD symptoms was observed as reflected by the drop in the total C-PDQ39 score in the non-DSQ group. Although there was a significant difference in total C-PDQ39 scores for the DSQ and
non-DSQ groups at week 16, this was not the case for the scores at weeks 8 and 24.
Discussion In Parts 1 and 2, although DSQ was present in non-PD participants, the frequency of DSQ was 2.5 times higher in PD participants. In addition, DSQ in PD participants was in general more severe than in non-PD participants. There was a close positive correlation between H&Y stage and DSQ, as well as between total C-PDQ39 score and DSQ. Age also showed positive correlation with DSQ in PD participants, while similar correlation was not observed in non-PD participants. Since PD is a slow progressive disease, it is reasonable that older PD participants showed more severe PD symptoms. The correlation between age and DSQ in PD participants may be due to correlation of PD with age. For Part 3, there was variation in the presence of DSQ, parameters suggesting that DSQ is reversible. However, in this study most participants with PD eventually developed symptoms of DSQ. Based on results in Part 1, non-DSQ PD participants should have lower total C-PDQ39 scores than DSQ PD participants. The fluctuation of C-PDQ39 in the nonDSQ PD group could be related to the small sample size (n Z 3 only). In this case, even a small change in a single
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Spleen qi deficiency in Parkinson disease
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Table 1 Comparison of DSQ between PD and non-PD participants in Parts 1 and 2.a Parameter
PD group (n Z 187)
Non-PD group (n Z 30)
P
Participants with DSQ (%) Sex: M (%) F (%) Age Total DSQ score Q1-dyspepsia Q2-fatigue Q3-abdominal distention Q4-abnormal defecation Q5-listlessness Q6-dysgeusia Q7-abdominal pain Q8-nausea Q9-gastric discomfort Q10-gurgling sound Q11-sallow complexion Q12-edema Q13-weakness to defecate
170 (90.9) 103 (89.6) 67 (93.1) 65 15 85 01 11 00 00 11 01 00 00 00 01 11 01 23
11 (36.7) 2 (22.2) 9 (42.9) 64 12 43 01 10 00 00 10 00 00 00 01 00 11 00 00
>.001b .006b .828c >.001c .756c .219c .812c .162c .138c .019c .449c .663c .322c .034c .012c .157c >.001c
Abbreviations: DSQ: deficiency of spleen qi; PD: Parkinson disease. a Data are expressed as median interquartile range (IQR). b PD group with DSQ compared with non-PD group with DSQ by Chi-square test. c PD group with DSQ compared with non-PD group with DSQ by ManneWhitney U test.
Table 2
subject would induce a great variation in the statistical results. In general, results of Part 3 indicate that PD symptoms may vary over time in PD individuals with DSQ, but remain relatively stable in PD individuals without DSQ. In Part 1, we observed a drop in daily L-dopa intake in PD participants with H&Y stage 4 despite the fact their disease duration was the longest. This may be due to complications of advanced PD, such as dyskinesia. Hence, L-dopa daily intake and duration as well as PD duration might not be positively correlated with DSQ because all PD participants exhibited DSQ in the advanced H&Y stages. On the other hand, the percentage of PD participants with DSQ was positively correlated with the H&Y stage and total C-PDQ39 score. The baseline medical histories of PD participants with and without DSQ in Part 1 were very similar. There was only a small proportion of participants with advanced H&Y stages. Thus, the progression of PD might be regulated by treating DSQ as it is closely related to the general condition of PD. In TCM, the term “spleen” refers to the energy pathway that controls the production of blood and vital energy (qi), which corresponds to the digestive system in biomedicine. From the results in Part 1, PD participants with DSQ presented with dysgeusia (DSQ-Q6), sallow complexion (DSQQ11), and weakness to defecate (DSQ-13). Hence, we recommend that TCM treatment of DSQ in persons with PD should focus on these symptoms. This study has limitations. The sample sizes in all three parts were small. Although the total number of subjects included in each part was larger than 30, each subgroup numbered less than 30. Small numerical variation within a subgroup may cause large statistical variation in the analysis. In fact, it was hard to determine the appropriate sample size at the beginning of the study because there was no previous research data or information on DSQ frequency, neither for persons with PD nor without PD. This research
Comparison between DSQ and non-DSQ PD participants in Part 1.a
Parameter
PD with DSQ (n Z 170)
PD without DSQ (n Z 17)
P
Sex, M/F Age, y H&Y stages Disease duration, y L-dopa duration, y L-dopa dosage, mg/d C-PDQ39 Total Score D1-mobility D2-activities of daily living D3-emotional well-being D4-stigma D5-social support D6-cognitions D7-communication D8-bodily discomfort
103/67 65.0 15 2.00 1 4.0 5.0 2.0 4.5 300.00 350.00 45.50 37 16.00 16 7.00 9 5.00 8 4.50 5 1.00 3 5.00 4 2.00 3 4.00 4
12/5 65.0 15 2.00 1 3.0 4.0 1.0 3.5 300.00 350.00 14 30 4.00 7 2.00 6 2.00 3 2.00 5 0.00 0 2.00 3 0.00 2 1.00 3
.419b .828c .043c .347c .133c .234c >.001c >.001c .001c >.001c .016c .009c .001c .001c >.001c
Abbreviations: C-PDQ39: Chinese version of the Parkinson Disease Questionnaire 39; DSQ: deficiency of spleen qi; H&Y: Hoehn and Yahr; PD: Parkinson disease. a Data are expressed as median interquartile range (IQR). b PD group with DSQ compared with PD group without DSQ by Chi-square test. c PD group with DSQ compared with PD group without DSQ by ManneWhitney U test.
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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K.-K. Chua, M. Li Table 3
Basic information based on H&Y stages in Part 1 PD participants.a
Parameter
H&Y 1 (n Z 60)
H&Y 2 (n Z 92)
H&Y 3 (n Z 23)
H&Y 4 (n Z 12)
Sex, M/F Age, y Disease duration, y L-dopa duration, y L-dopa dosage, mg/d Number of DSQ (%) Total DSQ score Total C-PDQ39 score
40/20 61.3 (9.7) 3.0 (2.6) 1.8 (2.4) 240.00 (214.48) 52 (86.7) 6.58 (3.19) 33.63 (20.36)
56/36 64.6 (9.4) 5.7 (5.2) 3.9 (4.6) 333.15 (295.23) 83 (90.2) 8.39 (4.33) 46.34 (23.78)
14/9 65.3 (9.4) 7.9 (5.3) 4.8 (4.2) 673.91 (695.58) 23 (100) 10.39 (5.18) 62.04 (20.93)
5/7 69.8 (8.2) 8.7 (9.2) 5.7 (5.2) 529.17 (443.36) 12 (100) 11.08 (4.68) 85.83 (26.35)
Abbreviations: C-PDQ39: Chinese version of the Parkinson Disease Questionnaire 39; DSQ: deficiency of spleen qi; H&Y: Hoehn and Yahr; PD: Parkinson disease. a Data are expressed as mean (SD) except sex ratio.
Table 4
Baseline characteristics of PD participants in Part 3.a
Parameter
PD with DSQ (n Z 44)
PD without DSQ (n Z 3)
P
Sex, M/F Age, y Disease duration, y L-dopa duration, y L-dopa dosage, mg/d H&Y stages DSQ total score C-PDQ39 total score
30/14 62.0 14 4.0 3.8 3.3 4.0 300.00 300 2.00 0.00 5.50 4 18.50 19
3/0 60.0 6.0 2.0 300.0 2.00 2.00 30
.244b .206c .742c .161c .692c .279c .029c .983c
Abbreviations: C-PDQ39: Chinese version of the Parkinson Disease Questionnaire 39; DSQ: deficiency of spleen qi; H&Y: Hoehn and Yahr; PD: Parkinson disease. a Data are expressed as median interquartile range (IQR). b PD group with DSQ compared with PD group without DSQ by Chi-square test. c PD group with DSQ compared with PD group without DSQ by ManneWhitney U test.
Table 5
Week 0 Dropout Week 8 Dropout Week 16 Dropout Week 24 Dropout
Variation in DSQ throughout the 24 weeks in Part 3. DSQ group (Male/Female)
Non-DSQ group (Male/Female)
With DSQ
Without DSQ
With DSQ
0/0
0/0
30/14 0/0 27/11
1/3
1/0
2/0 0/0
2/2
1/0
4/0 24/14
3/0 0/0
2/0 24/12
Without DSQ
2/0 0/0
0/0
3/0
6/0
0/0 0/0
Abbreviation: DSQ: deficiency of spleen qi.
provides important, hitherto missing, basic information on the occurrence rate of DSQ and the possible factors affecting DSQ in PD subjects. The trends revealed in this small study indicate that a larger scale study of DSQ prevalence would be justified and likely be productive.
A second limitation occurred with the sex differences in the PD and non-PD groups with regard to DSQ. As mentioned, males are more likely to have PD than females. Thus, it was reasonable to have more male PD participants in the study. However, for the non-PD groups, many more females were willing to be part of the study than males. Males were not willing to be interviewed for a number of reasons. For example, they assumed they were healthy or they did not want to share personal information with an unknown person. Thus, female participants in both the PD and non-PD groups exhibited higher frequencies of DSQ, which may have impacted the comparison of DSQ occurrence between the sexes. Therefore, a larger scale study on the relationship between DSQ and the sexes is suggested. Yet another limitation of the study was the geographically small sampling area for Part 2. Because the non-PD participants of Part 2 were recruited in a small area, the frequency of DSQ in these non-PD participants might not represent the whole population perfectly. Even so, these individuals were recruited from the entire three regions in Hong Kong, i.e. Eastern District of Hong Kong Island, Yau Tsim Mong District of Kowloon, and Sai Kung District of the New Territories. Thus, the Part 2 sample may still exhibit a trend of DSQ in Hong Kong non-PD participants.
Conclusions More than 90% of persons with PD who participated in this study exhibited DSQ, which was 2.5 times that of non-PD participants. In general, DSQ was more serious in PD than in non-PD participants. Furthermore, in PD participants, there was a positive correlation between severity of DSQ and severity of their PD symptoms. More participants in the advanced H&Y stages of PD had DSQ. Although there was some fluctuation in DSQ parameters over time, all PD participants developed DSQ by the end of the study. These clear trends suggest that DSQ could be helpful both in diagnosis and treatment of PD. Therefore, larger investigations on the prevalence of DSQ in persons with PD are needed to validate our results. Finally, TCM resolves DSQ through a number of modalities, including acupuncture and herbs, and these modalities should be continued to be studied for new, effective therapies for PD.
Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002
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Spleen qi deficiency in Parkinson disease Table 6
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Changes in total C-PDQ39 score throughout 24 weeks in Part 3.
Parameter (number of subjects at Week 0)
PD with DSQa (n Z 44)
PD without DSQb (n Z 3)
P
Difference at Week 8 (n) Difference at Week 16 (n) Difference at Week 24 (n)
3.00 14.50 (n Z 42) 4.00 12.25 (n Z 40) 5.50 14.50 (n Z 38)
10.00 (n Z 3) 10.00 (n Z 3) 0.00 (n Z 3)
0.069c 0.047c 0.423c
Values are given as median interquartile range (IQR) (n Z number of subjects at that time point). Values are the score changed within the same group between each time point and baseline (score at measurement point minus score at baseline). c Score changes in PD with DSQ compared with score changes in PD without DSQ at each time point by ManneWhitney U test. a
b
Competing interests The authors declare that they have no competing interests.
Author roles The authors’ contributions are as follows: KK Chua conceived the project and coordinated all efforts in the trial; M Li monitored the trial and contributed to the design of the trial; KK Chua and M Li helped with data analysis, discussion and wrote the paper.
Acknowledgements This work is part of the thesis by Stroke and Clinical Neurosciences (CNS) Master Programme, The Chinese University of Hong Kong (CUHK). It was supported by research grants (SCM/10-11/03, IRMS/12-13/1A) from Hong Kong Baptist University and Mr. & Mrs. Ko Chi Ming Center for Parkinson’s Disease Research. The authors would like to thank Prof. Vincent Mok and Prof. Adrian Wong from CUHK for their technical support as well as Prof. Shu-Leong Ho and Dr. KinLun Tsang for providing the Chinese version of Parkinson’s Disease Questionnaire 39. Also, thanks to Dr. Feng Sun and Ms. Vicky Keng from the Clinical Division, School of Chinese Medicine, HKBU for their great support on this study. The authors would also like to thank Dr. Martha Dahlen for her English editing of this manuscript.
Appendix A. Supplementary data Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.jtcms.2017.03.002.
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Please cite this article in press as: Chua K-K, Li M, Occurrence of spleen qi deficiency as defined by Chinese medicine in Parkinson disease, Journal of Traditional Chinese Medical Sciences (2017), http://dx.doi.org/10.1016/j.jtcms.2017.03.002