Pattern, or “zheng,” differentiation is the essential guide to treatment with traditional Chinese medicine (TCM). However, the considerable variability between TCM patterns complicates evaluations of TCM treatment effectiveness. The aim of this study was to explore and characterize the relationship between patterns and the core patterns of allergic rhinitis. We summarized 23 clinical trials of allergic rhinitis with mention of pattern differentiation; association rule mining was used to analyze TCM patterns of allergic rhinitis. A total of 205 allergic rhinitis patients seen at Chang Gung Memorial Hospital from March to June 2005 were included for comparison. Among the 23 clinical trials evaluated, lung qi deficiency and spleen qi deficiencies were the core patterns of allergic rhinitis, accounting for 29.50% and 28.98% of all patterns, respectively. A higher prevalence of lung or spleen qi deficiency (93.7%) was found in Taiwan. Additionally, patients with lung or spleen qi deficiency were younger (
Traditional Chinese medicine (TCM) has been used for centuries in China and more recently has been widely studied and applied throughout the world [
Pattern differentiation, or “zheng,” is a unique TCM concept that summarizes the nature, location, and pattern of diseases corresponding to the World Health Organization’s definition [
Due to the considerable variability in individual practices, it can be difficult to summarize TCM clinical data by conventional statistical techniques, and thus a number of data mining methods, such as association rule mining (ARM) and cluster analysis, are used to acquire TCM knowledge from large-scale clinical data [
Allergic rhinitis, a common immunologic disorder, affects 10% to 20% of the world’s population [
Several TCM treatments have been beneficial for allergic rhinitis, and the results of many studies have outlined the possible mechanisms for suppressing allergic reactions [
The aim of this study was to explore the core TCM patterns of allergic rhinitis by using ARM and to compare these results with a hospital-based database to identify crucial factors to differentiate the patterns of allergic rhinitis. Depending upon the results of this study, future studies could focus on the most important TCM patterns, and different treatments could then be designated for specific TCM patterns.
First, we conducted an extensive search of several databases, including PubMed, MEDLINE, Web of Science, Scopus, and the China Academic Journals Full-Text Database (CJFD). Keywords searched included “allergic rhinitis,” “bi qiu,” “chronic rhinitis,” “pattern differentiation,” “syndrome differentiation,” “zheng,” and “clinical trials.” “Bi qiu” is the TCM disease corresponding to allergic rhinitis in WM. The full text of the search results was accumulated and critiqued by all authors of this study, and disagreements were resolved by consensus. After critical appraisal, the essential elements, including case number, gender, age, diagnostic criteria, and distribution of TCM patterns, were extracted from the eligible clinical trials manually. All these elements were entered into the computerized database.
ARM, a data mining technique developed in the 1990s, has been widely used in medical research to explore the relationships among TCM prescriptions, disease comorbidities, and TCM patterns [
To compare ARM results from the clinical trials database and practical clinical data, we used an established database of allergic rhinitis patients in the TCM outpatient service at CGMH. The definitive diagnosis of allergic rhinitis and TCM patterns was confirmed by Dr. Yang. Detailed data, including TCM patterns, age, gender, parents’ health history, patients’ personal health history, residence, serum IgE levels, results of MAST (Multiple Allergen Simultaneous Test panel) tests, and symptom severity, were recorded in this database. All data were collected with informed consent, and the records from March to June 2005 were extracted for further analysis. The process of data collection and analysis was approved by the Institutional Review Board (IRB) of CGMH.
To examine the differences in characteristics among TCM patterns Student’s
A total of 114 studies were found by the search strategy, and after detailed appraisal, 23 studies were eligible for inclusion in the study. All 23 studies were done in China and had been published in Chinese. Studies with English titles are listed as examples in the Appendix. From the 23 eligible studies, 2589 patients were identified, and a patient-pooled database was constructed. Fifteen patterns composed of one or more organs and the nature of disease were identified. Lung qi deficiency was the most common pattern (23.95%), followed by spleen qi deficiency (22.75%), and lung yang deficiency with wind-cold assailing the lung (14.75%). More than half of patients were classified into the qi deficiency pattern in these trials. In contrast, blood stasis, dual deficiencies of qi and yin of lung, and lung-spleen yang deficiency were the least-recognized patterns, and all had a prevalence of less than 1% (Table
All TCM patterns of 23 clinical studies for allergic rhinitis.
Patterns | Number of patients | Percentage |
---|---|---|
Lung qi deficiency | 620 | 23.95% |
Spleen qi deficiency | 589 | 22.75% |
Lung yang deficiency pattern with wind-cold assailing the lung | 382 | 14.75% |
Phlegm-heat obstructing the lung | 232 | 8.96% |
Dampness-phlegm obstructing the lung | 210 | 8.11% |
Kidney yang deficiency | 185 | 7.15% |
Kidney qi deficiency | 104 | 4.02% |
Dual deficiency of the lung-spleen qi | 57 | 2.20% |
Dual deficiency of the spleen-kidney qi | 54 | 2.09% |
Qi stagnation and blood stasis | 46 | 1.78% |
Dual deficiency of the lung-kidney qi | 42 | 1.62% |
Lung-kidney yin deficiency | 27 | 1.04% |
Lung-spleen yang deficiency | 19 | 0.73% |
Dual deficiency of qi and yin of lung | 17 | 0.66% |
Blood stasis | 5 | 0.19% |
| ||
Total | 2589 |
After applying ARM, we identified the 10 most common relationships between the locations and nature of disease patterns (Table
The 10 most common relationships of TCM patterns among 23 clinical studies for allergic rhinitis.
Relationship of pattern | Support | Confidence |
---|---|---|
Lung with qi deficiency | 29.50% | 47.35% |
Spleen with qi deficiency | 28.98% | 97.63% |
Lung with cold | 15.40% | 24.72% |
Heat with lung | 8.61% | 100.00% |
Phlegm-dampness with lung | 7.79% | 100.00% |
Lung with qi deficiency | 7.64% | 48.70% |
Kidney with cold | 7.05% | 44.92% |
Lung and spleen with qi deficiency | 4.71% | 86.99% |
Kidney and spleen with qi deficiency | 2.00% | 100.00% |
Kidney and lung with qi deficiency | 1.78% | 64.00% |
The associations between different TCM patterns of allergic rhinitis. Note: the width of connection lines represents the prevalence of the associations.
Additionally, high confidence, as high conditional probability, was found among three conditions: “heat with lung,” “phlegm-dampness with lung,” and “kidney and spleen with qi deficiency.” It is assumed that, for patients with allergic rhinitis, once heat or phlegm-dampness was found, the nature of these two diseases would always be combined with lung, forming a pattern. More interestingly, qi stagnation and blood stasis were strongly associated, and neither had any relationship with major organs, such as lung, spleen, or even kidney. Despite the fact that this group’s prevalence was only 0.19%, it may represent special mechanisms or manifestations of allergic rhinitis.
Using the well-established allergic rhinitis patient database at CGMH, TCM pattern analysis showed these patients could be divided into 3 groups: those with lung qi deficiency, dual deficiency of lung-spleen qi, and kidney qi deficiency (Table
Characteristics of TCM patterns of 205 allergic rhinitis patients at Chang Gung Memorial Hospital.
Lung qi deficiency | Dual deficiency of the lung-spleen qi | Kidney qi deficiency |
|
|
---|---|---|---|---|
Number of cases | 137 | 55 | 13 | |
Age, mean ± SD† | 29.07 ± 13.17 | 25.29 ± 12.03 | 57.53 ± 12.96* | <0.0001 |
Patients gender | 0.690 | |||
Male | 58 | 27 | 6 | |
Female | 79 | 28 | 7 | |
Parents’ history of allergic diseases | 0.234 | |||
None | 70 | 24 | 9 | |
One | 58 | 24 | 2 | |
Both | 9 | 7 | 2 | |
Personal history | ||||
Asthma | 16 | 6 | 2 | 0.903 |
Atopic dermatitis | 21 | 12 | 1 | 0.370 |
Urbanization level | 0.423 | |||
Urban | 93 | 32 | 9 | |
Rural area | 44 | 23 | 4 | |
IgE level (IU/mL) mean ± SD† | 335.05 ± 456.07 | 420.90 ± 778.82 | 255.744 ± 433.59 | 0.494 |
MAST allergy test (positive/negative) | 60/19 | 25/12 | 2/4 | 0.070 |
Symptom severity, mean ± SD† | 4.33 ± 2.08 | 4.64 ± 2.05 | 3.15 ± 2.23 | 0.072 |
† SD: standard deviation.
TCM pattern differentiation was mainly based on clinical symptoms and therefore analysis of patients’ symptom severity provided decisional information for pattern differentiation. Higher symptom severity scores, equivalent to more severe symptoms, were noted in the lung qi deficiency group and dual deficiency of the lung-spleen qi group, compared to the kidney qi deficiency group, although this was not statistically significant (Table
Relations between severity of symptoms and TCM patterns.
Lung qi deficiency or spleen qi deficiency‡ | Kidney qi deficiency |
|
|
---|---|---|---|
|
|
||
Total score, mean ± SD† | 4.42 ± 2.07 | 3.15 ± 2.23 | 0.068 |
Sneezing, mean ± SD† | 1.39 ± 0.98 | 1.08 ± 1.19 | 0.278 |
Running nose, |
1.68 ± 1.02 | 1.46 ± 1.05 | 0.453 |
Stuffiness, mean ± SD† | 1.35 ± 0.89 | 0.62 ± 0.65 | 0.004* |
Key:
To the best of our knowledge, this is the first study to investigate the TCM patterns of clinical trials and to provide comparisons of clinical hospital-based data and severity of symptoms. The use of TCM has become much more widespread in recent years and many more interventions guided by TCM theory are being integrated into modern medicine [
From the viewpoint of evidence-based medicine, in future studies, it will be particularly important to summarize TCM patterns and to explore core patterns of disease. ARM is an appropriate statistical method for summarizing disease patterns and exploring core patterns and the nature and locations of diseases because it examines not only the prevalence of a pattern but also the strength of relations between and within patterns [
Qi deficiency has been proved to be crucial to allergic rhinitis in previous studies, and two famous qi-tonifying Chinese herbal products, Bu-zhong-yi-qi-tang and Xiang-sha-liu-jun-zi-tang, have had marked therapeutic effects on allergic rhinitis, even without pattern differentiation [
Lung and spleen are the two important locations of diseases and are highly related to qi deficiency, forming TCM patterns. The function of lung, from the viewpoint of TCM, includes control of respiration, qi domination, and fluid regulation, and these functions are highly related to the nose and skin [
The spleen, from the viewpoint of TCM, dominates transformation of food to energy, similar to WM’s view of the gastrointestinal tract’s function [
Yin and yang deficiencies are less commonly identified than qi deficiency in clinical trials, and they were also absent in the surveillance at our hospital. Yin deficiency was a specialized TCM pattern characterized by decreased body fluids, and it was diagnosed when patients complained about dryness of the mouth, throat, and nasal passages, or constipation. Additionally, a reddish tongue with scanty coating and a fine, rapid pulse were commonly seen among such patients. Moreover, symptoms of yang deficiency among allergic rhinitis patients included manifestations of qi deficiency with prominent fear of cold, cold extremities, clear nasal discharge, pale face, and an enlarged tongue with a white, slick coating. Both lung yin and yang deficiencies were noted in the late stage of the clinical course of allergic rhinitis, and they usually developed when qi deficiency, the early stage of allergic rhinitis, was not properly treated. Therefore, it is reasonable that combinations of qi and yin deficiency or yang deficiency were less frequently found among allergic rhinitis patients.
Additionally, combination of qi stagnation and blood stasis was a special pattern in this study. Although the prevalence was low, about 1.78%, a strong association with allergic rhinitis was found (Tables
The severity of nasal stuffiness, one of the common symptoms of allergic rhinitis, is definitely different between lung or spleen qi deficiency and kidney qi deficiency groups. In this study, the patients in the kidney qi deficiency group were older than those in the lung or spleen qi deficiency group. This finding is similar to that of previous studies. Currently, nasal stuffiness is thought to be caused by eosinophil and mast cell infiltration with subsequent airway remodeling. It is believed to be related to certain neuropeptides, and its severity decreases with aging [
Though the clinical data are closely comparable to the summarized results of clinical trials for allergic rhinitis, there are still some limitations to this study. First, the quality of clinical trials is heterogeneous. Some population characteristics, such as gender, age, or detailed manifestations of allergic rhinitis, are not provided in every trial, and therefore selection bias may exist. To effectively eliminate this bias, only the most representative trials of allergic rhinitis were included in this study after strict evaluation. Although the number of cases was considerably reduced, the result of ARM is highly reliable, since trials enrolled in this study firmly focus on TCM patterns of allergic rhinitis. Second, the definition of TCM patterns is not exactly the same among these studies, and the basis of pattern differentiation includes Chinese expert consensus on allergic rhinitis in 1997 and 2004, and a textbook of TCM otolaryngology. This disadvantage was largely overcome by examining the descriptions of patterns in every trial and validating them by TCM doctors. Furthermore, results of statistical analysis on large-scale pooled clinical trials are similar to the consensus among TCM experts and thus can overcome the variability of patterns differentiation.
Core TCM patterns were explored in this study by applying ARM to clinical trials of allergic rhinitis, and the summarized result is comparable to hospital-based data. A younger patient population and greater severity of nasal stuffiness were associated with the most important patterns, lung or spleen with qi deficiency. Future investigations of TCM treatment for allergic rhinitis can be designed on the basis of these results, and may help define a specific TCM pattern.
For more details see Tables
Clinical trials of allergic rhinitis included in this study*.
Study | Number of patients | Age |
Patterns description (cases) |
---|---|---|---|
Yang et al. [ |
216 | 36.2; 7–63 | Lung qi deficiency: 100 |
Spleen qi deficiency: 71 | |||
Kidney qi deficiency: 45 | |||
| |||
Liu et al. [ |
242 | 42.6† | Lung yang deficiency pattern with wind-cold assailing the lung: 167 |
Phlegm-heat obstructing the lung: 23 | |||
Spleen qi deficiency: 32 | |||
Kidney yang deficiency: 20 | |||
| |||
Tang et al. [ |
70 | 28.95† | Lung yang deficiency pattern with wind-cold assailing the lung: 24 |
Phlegm-heat obstructing the lung: 16 | |||
Spleen qi deficiency: 20 | |||
Kidney yang deficiency: 14 | |||
| |||
Qiu et al. [ |
256 | 32.52; 7–70 | Lung qi deficiency: 124 |
Phlegm-heat obstructing the lung: 32 | |||
Spleen qi deficiency: 72 | |||
Kidney yang deficiency: 28 | |||
| |||
Lu et al. [ |
106 | 31, 4–82 | Lung qi deficiency: 60 |
Dual deficiency of the lung-spleen qi: 21 | |||
Dual deficiency of the lung-kidney qi: 25 |
* Studies without titles or an abstract in English are not listed in this table.
† Range of age was not provided by the authors.
Symptom severity assessment of allergic rhinitis.
Symptoms | Presentation | Score |
---|---|---|
Sneezing | None | 0 |
1–5 times/day | 1 | |
6–10 times/day | 2 | |
>10 times/day | 3 | |
Runny nose | None | 0 |
1–5 times/day | 1 | |
6–10 times/day | 2 | |
>10 times/day | 3 | |
Stuffiness | None | 0 |
Mild, without mouth-breathing | 1 | |
Moderate, with occasional mouth-breathing | 2 | |
Severe, with frequent mouth-breathing | 3 |
The authors especially thank Dr. Peifang Cai for collecting clinical data for this study.