Efficacy and safety of Tuomin Zhiti decoction (脱敏止嚏汤) on patients with seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial

Abstract

OBJECTIVE:

To evaluate the clinical efficacy and safety of Tuomin Zhiti decoction (脱敏止嚏汤, TZD) in the short-term treatment of seasonal allergic rhinitis (SAR).

METHODS:

This study is a randomized, double-blind placebo-controlled, and single-center clinical trial. In April 2021, during the spring pollen season in Beijing, 94 SAR patients aged 19-60 years were randomized (1:1 ratio) to receive two weeks of TZD or placebo. The primary outcomes were the change of Total Nasal Symptom Score (TNSS) and Total Ocular Symptom Score (TOSS) from baseline to the end of treatment. Secondary outcomes were the changed score of the mini Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Rescue Medication Score (RMS), and Patient Global Impression of Change (PGIC). All adverse events were recorded and evaluated by two senior physicians.

RESULTS:

TZD significantly reduced both the total nasal symptom scores and total ocular symptom scores compared to scores at baseline, while the placebo group showed an increasing trajectory in both symptom scores. Compared to the placebo group, the TZD group also showed a greater improvement in the quality of life, scores of RMS, nasal and eye symptoms scores after TZD treatment (P < 0.001). Most notably, at the end of treatment, the proportion of remission measured by PGIC was significantly higher in the TZD group (82.97%) compared with the placebo group (47.72%, P < 0.001).

CONCLUSION:

This study suggested that two weeks of TZD is an effective and safe treatment for SAR patients and spring pollen allergy, TZD could significantly improve the nasal and eye symptoms and improve the quality of life of patients.

1. INTRODUCTION

Allergic rhinitis (AR) is an allergic inflammation of the nasal mucosa characterized by symptoms such as nasal blockage, running nose, repeated sneezing, fatigue, thus AR could seriously affect the quality of life of patients. It can be induced by a wide variety of allergens, including dust, animal dander and pollen.^1,2 Depending on the type of allergen, the disease can be divided into seasonal AR (SAR) and perennial AR. SAR is often seasonal, with symptoms most notably during the spring, when allergens such as juniper, sycamore and ash are in abundance.

The common symptom-controlling treatments include nasal corticosteroids, antihistamine, and allergen immunotherapy.³ These treatments, while recommended by the official guidelines, may not be an optimal solution for AR patients in the long term.⁴ Moreover, long-term use of drugs may lead to a wide variety of adverse effects, ranging from drowsiness and fatigue to severe headaches, palpitations, and even high blood pressure and other cardiovascular problems.⁵ Given that the current treatments are unsatisfactory, further research for AR treatments with better therapeutic effects or fewer side effects is essential.⁶ An increasing number of clinicians and patients are looking for complementary and alternative medicines to treat AR, such as Chinese herbal medicine.⁷ In recent years, a growing number of studies have produced promising results on the curative effect of Traditional Chinese Medicine (TCM) treatment on AR, all with relatively few side effects.^6-11

In TCM, the condition of AR is referred to as “Bi Qiu”.¹⁰ According to TCM theory, the dysfunction of lung Qi plays an important role in the pathogenesis of “Bi Qiu”. This dysfunction can be triggered by both external and internal pathogenic factors and is frequently observed in conjunction with weaken Qi in both the spleen and kidney systems.¹² TZD is a formula made up of ten different herbs, including Xinyi (Flos Magnoliae Biondii Immaturus), Cangerzi (Fructus Xanthii), Wumei (Fructus Mume), Chantui (Periostracum Cryptotympanae), Fangfeng (Radix Saposhnikoviae), Lingzhi (Ganoderma Lucidum), Huangqi (Radix Astragali Mongolici), Huangqin (Radix Scutellariae Baicalensis), Wuweizi (Fructus Schisandrae Chinensis) and Baizhi (Radix Angelicae Formosanae). These herbs collectively function to tonify lung Qi and dredge the nasal orifice. Previous study have demonstrated that TZD could decrease the AR-induced damage to the nasal mucosa, and clearly ameliorate nasal symptoms through reducing Ovalbumin (OVA)-specific immunoglobulin E (IgE) and histamine release.¹¹ However, the clinical trial evaluating the efficacy and safety in humans is still in lack.

Therefore, the present study aims to evaluate the clinical efficacy and safety of this prescription in patients with AR and provide high-quality evidence to support its clinical application.

2. METHODS

2.1. Study design

This study was a randomized, double-blind, placebo-controlled, and single-center clinical trial. The objective was to demonstrate the clinical efficacy and safety of TZD in SAR. This trial was registered with the China Clinical Trial Registration Center (No. ChiCTR2100044839).

According to the randomization code generated by the computer, eligible participants were randomized (1:1) to receive 7 g of TZD or placebo two times a day for 2 weeks. During the study period, desloratadine (tablets) was distributed free of charge to all participants as rescue medications to relieve AR symptoms. Except for research and emergency medications, all participants were asked not to use any other medications that could relieve allergy symptoms.

AR status and related medicine history starting from last spring were collected from all participants through a series of routine retrospective questionnaires before the trial to get a baseline impression of past treatment effectiveness, including Patient Global Impression of Change (PGIC), Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS) and mini Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were recorded before and after treatment. Rescue Medication Score (RMS) and PGIC were used during treatment were recorded at the end of treatment. During the treatment period, an additional questionnaire collecting nasal and eye symptoms was distributed digitally on the seventh day (1 week). The use of rescue medication as well as any occurrence of adverse events (AEs) observed during the trial were also monitored and recorded in daily questionnaires.

2.2. Ethics approval and consent to participates

Study designs and protocols were approved by the corresponding ethics committee. This research adhered to the principles of the Declaration of Helsinki and complied with the legal framework governing medical research involving human subjects. The trial was registered in ChiCTR (ChiCTR-INR-16010063) on March 30, 2021. Informed consent was obtained voluntarily from each participant.

2.3. Patients

Participants were recruited from the Department of Allergy of the Beijing TongRen Hospital between January and March 2021. A total of 94 adults were included in accordance with the inclusion criteria below and were randomized into 2 groups (46 in the placebo group and 48 in the TZD group).

The inclusion criteria were as follows: (a) aged 18-60 years; (b) clinical history of spring SAR for at least 2 years, with/without conjunctivitis; (c) symptom scores of ≥ 2 points for two or more nasal symptoms (sneezing, rhinorrhea, nasal itching, and nasal obstruction) and for at least one conjunctival symptom (ocular itching/ grittiness/redness and ocular tearing) during the April pollen season for the last 2 years; (d) sensitization to at least one of the main spring pollens (juniper, sycamore, ash, or trees), as confirmed by an allergen-specific IgE test using the Euroline system (EUROIMMUN, Beijing, China) or a skin prick test less than one month before the start of this trial; (e) long-term resident of Beijing and will remain in Beijing during the study period.

The exclusion criteria were as follows: (a) any other nasal disorders (e.g., non-AR or chronic rhinosinusitis with/without polyps) or infectious diseases (e.g., upper respiratory tract infection or infectious eye disease) that could possibly interfere with the evaluation of the study; (b) comorbid atopic dermatitis or asthma; (c) history of hypersensitivity to Chinese herbal medicine, other antihistamines, or any ingredients in the study drug; (d) treated with a systemic glucocorticoid within 4 weeks or oral antihistamine and intranasal corticosteroid within 2 weeks prior to recruitment; (e) treated with TCM within 4 weeks prior to recruitment; (f) treated with allergen-specific immunotherapy for pollens within the last 2 years; (g) or during study participation in any other clinical trial within 3 months prior to screening; (h) women who were breastfeeding, pregnant, possibly pregnant, or wishing to be pregnant; (i) serious medical conditions, such as malignant tumor, hematologic diseases, mental disorders, or cardiovascular diseases.

2.4. TZD and placebo

TZD is a 10-herb formula that is based on TCM theory. The intervention group was treated with TZD granule and the control group was treated with a placebo of TZD (7 g) two times a day for 2 weeks. The placebo for TZD granules was composed of starch and edible coloring, and it matched the appearance and taste of TZD granules as closely as possible, with the same dosage. However, it lacked the active ingredients. TZD and the placebo were manufactured in accordance with Good Manufacturing Practice by Guangdong Yifang Pharmaceutical Co. Ltd. (Foshan, China; production batch number YF21032601; production license number: Guangdong 20160214).

2.5. Outcomes

The primary outcomes were the TNSS and TOSS. The secondary outcomes included mini RQLQ, RMS, and PGIC.

TNSS was used to evaluate nasal symptoms (runny nose, nasal itching, nasal congestion, and sneezing). TOSS was used to evaluate ocular symptoms (ocular redness/itching and ocular tearing). Each symptom was divided into four grades in accordance with the degree as follows: 0 = no symptom, 1 = mild symptom, 2 = moderate symptom, and 3 = severe symptom.¹³

The mini RQLQ for patients with nasal mucositis consisted of 14 questions and seven dimensions (activity limitation, sleep disturbance, nasal symptoms, ocular symptoms, other non-ocular/nasal symptoms, practical problems, and emotions). Each question was scored on scales of 0 = no distress, 1 = almost no distress, 2 = some distress, 3 = moderate distress, 4 = very distressed, 5 = severely distressed, and 6 = extremely distressed. Each dimension was scored separately, and the cumulative total score was denoted as the total RQLQ score.¹⁴

The RMS was evaluated with four grades: 0 = no rhinitis medication, 1 = oral antihistamine (1 × cetirizine 10 mg/d or equivalent), 2 = oral antihistamine (2 × cetirizine 10 mg/d (= 20 mg) or equivalent], 3 = systemic or topical corticosteroids for rhinitis.¹⁵ The patients’ needs to record the daily rescue medication used for rhinitis.

PGIC was assessed in accordance with a five-point scale of 0-4, with 0 = aggravated symptoms, 1 = no control over symptoms, 2 = minor control over symptoms, 3 = substantial control over symptoms, and 4 = total control over symptoms.¹⁶

2.6. Security indicators

Discomfort after taking the medicine (refers to symptoms, such as increased rhinitis symptoms, nausea, vomiting, abdominal pain, palpitations, dizziness, headache, itchy skin, diarrhea, constipation, decreased appetite, and insomnia). A specific record sheet was established.

2.7. Sample size

The sample size calculation is grounded on the primary outcome, the TNSS. Assuming equal variances, the effect size derived from a prior study is delineated as follows: The mean for the TZD group is assumed to be 1.16, and the placebo group exhibits a mean of 1.46, accompanied by a standard deviation of 0.55.¹⁷ Sample size calculations were conducted using PASS (ver 15.0.5, NCSS, LLC. Kaysville, Utah, USA), utilizing a two-sample t-test for differences under the null hypothesis that there is no significant difference in TNSS score changes between the treatment and placebo groups. The significance level (α) was set at 0.05 (two-sided), and the statistical power (1-β) was targeted at 0.8. Accounting for a projected dropout rate of 10%, a sample size of 47 participants per group was deemed necessary, resulting in an aggregate sample size of 94.

2.8. Definition of pollen season

The start and end dates of the grass pollen season were determined by official pollen count data. The starting day of pollen season was defined as the first of 5 consecutive days with a pollen count ≥ 10 grains/m³ of air, and the last day of pollen season was denoted as the first of 5 consecutive days with a pollen count < 10 grains/m³ of air.¹⁸

Based on Beijing’s spring pollen concentration data from the past few years, it is estimated that the Beijing spring pollen season of 2021 will be from mid-to-late March to late April. As such, to ensure that the treatment period falls within the spring pollen season, the treatment period was scheduled in April.

2.9. Randomization and blinding

The randomization number was made using SAS software 9.4 (SAS Institute, Cary, NC, USA) by the Centre for Evidence-based Chinese Medicine, Beijing University of Chinese Medicine (CEBCM-BUCM). All patients were included and randomly assigned to two groups at a ratio of 1:1. The randomization number table, drug coding, and emergency envelopes were made into random cards, put in small sealed envelopes, and given an identification number. The schedules will be sent to Guangdong Yifang Pharmaceuticals Co., Ltd. (Foshan, China). For drug packaging and preparation of the code break envelopes. During research period, the patients, data collectors, physicians, and researchers were blinded to the allocated postoperative protocol.

2.10. Statistical analysis

All data were analyzed using IBM SPSS Statistics (ver 25.0, IBM Corp., Armonk, NY, USA). The test was two-sided, and P value < 0.05 was considered statistically significant. Measurement data were descriptive statistics using mean ± standard deviation ($\overline{x}\pm s$), and count data were descriptive statistics using frequency (constituent ratio). Comparison of curative effects in each group was performed using χ ² test or nonparametric test. Changes in treatment nodes within each group were compared using a paired-sample t-test, and differences between groups were compared using independent-sample t-test. Graphical images were prepared in GraphPad Prism 9 (GraphPad Software, San Diego, CA, USA).

3. RESULTS

3.1. Baseline characteristics

A total of 94 participants met the criteria and were then randomized into two groups. Ninety-one participants (97%) completed the study, with 3 participants dropping out. One case was excluded because their rhinitis diary card was not filled out as required; another case was lost to follow-up after the intervention; and the final drop out was a participant who stopped taking the medicine due to a suspected pregnancy. The flow chart of this study is shown in Figure 1. 47 participants (23 male and 24 female) aged 19-59 years [(38.1 ± 10.4) years] were included in the TZD group, while 44 participants (21 male and 23 female) aged 22-58 years [(37.6 ± 8.3) years] were included in the placebo group. There was no statistically significant difference between the demographic and baseline characteristics of the two groups (Table 1).

Figure 1. Study participant flow diagram.

TZD: Tuominzhiti decoction. TZD group (7 g/pack, po, 1 pack/time, bid, for 2 weeks), placebo group (7 g/pack, po, 1 pack/time, bid, for 2 weeks).

Table 1.

Homogeneity test for general characteristics and measurement variables at baseline ($\overline{x}\pm s$)

Characteristic	TZD group (n = 47)	placebo group (n = 44)	P value
Age (years)	38.1±10.5	37.6±8.4	0.773a
Male/female	23/24	21/23	0.909a
TNSS
Sneezing	2.4±0.7	2.4±0.7	0.881a
Runny nose	2.1±0.8	2.2±0.7	0.898a
Itchy nose	2.4±0.7	2.3±0.9	0.199a
Nasal obstruction	2.0±0.9	2.0±1.0	0.357a
TOSS
Itching/redness	2.0±0.8	2.3±0.9	0.133a
Tearing	1.3±1.0	1.5±1.1	0.325a
Overall	12.0±3.5	12.5±3.7	0.200b
mini RQLQ score
Overall	44.8±15.5	49.2±17.2	0.122b
Activity limitation	9.2±4.2	10.8±4.4	0.055a
Practical problems	8.2±2.6	8.5±3.1	0.588b
Nasal symptoms	11.3±4.0	12.0±4.0	0.115a
Eye symptoms	9.9±4.1	10.1±5.3	0.507b
Other symptoms	7.0±4.3	7.7±4.4	0.256b

Notes: TNSS: total nasal symptom score; TOSS: total ocular symptom score; RQLQ: rhinoconjunctivitis quality of life questionnaire. TZD group (7 g/pack, po, 1 pack/time, bid, for 2 weeks), placebo group (7 g/pack, po, 1 pack/time, bid, for 2 weeks). ^aNon-parametric test; ^bIndependent samples t-test.

3.2. Clinical efficacy

The TNSS and TOSS were used as the primary outcome measure. While the TNSS and TOSS in the two groups showed no statistical difference before the start of treatment (P > 0.05). During the spring pollen period, the TNSS and TOSS in the TZD group decreased after treatment, reaching statistical significance at both the first and second week of the trial (P < 0.01) (Figure 2), indicating better control of symptoms in the TZD group compared to the placebo group (Table 2).

Figure 2. TNSS and TOSS for 1- and 2-week treatment periods.

TZD group (n = 47) (7 g/pack, po, 1 pack/time, bid, for 2 weeks), placebo group (n = 44) (7 g/pack, po,1 pack/time, bid, for 2 weeks). TNSS: total nasal symptom score; TOSS: total ocular symptom score. Difference between groups was tested by independent sample t-test or non-parametric test. Data are presented as mean ± standard deviation. Compared with baseline, ^aP < 0.001, ^bP < 0.01.

Table 2.

Effect of treatments on total nasal symptom score ($\overline{x}\pm s$)

Variable	TZD group (n = 47)	placebo group (n = 44)	P value
TNSS
Sneezing	1.3±0.7	1.9±0.8	0.001a
Runny nose	1.2±0.8	1.9±0.8	0.000b
Itchy nose	1.1±0.8	1.6±1.0	0.002a
Nasal obstruction	1.1±0.9	1.7±0.9	0.001a
TOSS
Itching/redness	1.0±0.9	1.5±1.0	0.024c
Tearing	0.5±0.8	0.9±0.9	0.014c
Overall	6.1±3.7	9.5±4.0	0.000b

Notes: TZD group (7 g/pack, po,1 pack/time, bid, for 2 weeks), placebo group (7 g/pack, po, 1 pack/time, bid, for 2 weeks). TNSS: total nasal symptom score; TZD: Tuominzhiti decoction; TOSS: total ocular symptom score. Difference between groups was tested by independent sample t-test or Non-parametric test, ^aP < 0.01, ^bP < 0.001, ^cP < 0.05.

The RMS and PGIC exhibited no significant difference across the two groups before the study. The RMS during treatment in the TZD group (0.15 ± 0.36) and placebo group (0.36 ± 0.61), with no statistically significant difference observed between the two groups (P > 0.05). The PGIC in the TZD group was significantly higher than that in the placebo group (P < 0.001). The proportion of symptom control as measured by the PGIC at the end of the study period was significantly higher in the TZD group (82.97%) than in the placebo group (47.72%, P < 0.001). In the TZD group, complete control was at 6.38%, basic control at 44.68%, and slight control at 31.91%. For the placebo group, basic control at 20.45%, and slight control at 27.27%.

3.3. Quality-of-life assessment

Before the treatment, there was no statistically significant difference in mini RQLQ scores between the TZD group and the placebo group (P > 0.05) (Table 2). A statistically significant improvement was observed in TZD group after the treatment (P < 0.001). The same relationship was also observed in all mini RQLQ subcategories (P < 0.01) (Figure 3).

Figure 3. Mean mini RQLQ score change for 2-week treatment period.

TZD group (n = 47) (7 g/pack, po, 1 pack/time, bid, for 2 weeks), placebo group (n = 44) (7 g/pack, po, 1 pack/time, bid, for 2 weeks). RQLQ: rhinoconjunctivitis quality-of-life questionnaire; TZD: Tuominzhiti decoction. Differences between groups were compared using independent-sample t-tests or nonparametric tests. Data are presented as mean ± standard deviation. Compared with baseline, ^aP < 0.001; compared with baseline, ^bP < 0.01.

3.4. Safety evaluation

Seven participants reported a total of seven adverse events (five in the TZD group and two in the placebo group): dry nose (two), gastrointestinal disorders (two), and nosebleeds (one) in the TZD group and dry nose (one), sore throat (one) in the placebo group. None of the adverse events were serious, and all were resolved with or without treatment.

4. DISCUSSION

In this study, TZD significantly relieved both nasal and eye symptoms of SAR, including running noses, nasal itching, nasal congestion, ocular redness/itching etc. Compared with the placebo group, the TNSS and TOSS in the TZD-treated group significantly decreased while quality of life improved. The evaluation of patient satisfaction after 2 weeks of treatment also showed the superiority of TZD in improving SAR. In addition, TZD treatment in the short term was found to be safe given that most patients reported no adverse reactions. To our knowledge, this is also the first study that provides promising clinical evidence on the use of TCM to treat SAR, which is especially meaningful given the timing of our intervention during Beijing’s pollen season.

The treatment options currently recommended in general guidelines are far from being optimal solutions to AR. For example, antihistamines and corticosteroids, have significant side effects, such as cardiotoxicity and drowsiness.¹⁹ Therefore, an increasing number of clinicians and patients are looking for complementary alternative medicines, such as Chinese herbal medicine, to treat AR. TCM has been known for allergy treatment for thousands of years.²⁰ Many studies have confirmed that TCM has anti-allergic and anti-inflammatory effects and is effective in the treatment of AR, it can regulate immune function, relieve symptoms, and reduce the frequency of allergic attacks.^10,21 Although the difference in the need for rescue antihistamine medication between the TZD group and the placebo group did not reach statistical significance, a trend toward lower usage was observed in the TZD group.

In TCM, the condition of AR is referred to as “Bi Qiu”. This condition typically manifests in several common patterns, including lung-Qi deficiency, spleen-Qi deficiency, kidney-Yang deficiency, and lung heat.¹⁰ According to TCM theory, the dysfunction of lung Qi plays an important role in the pathogenesis of “Bi Qiu”. This dysfunction can be triggered by both external and internal pathogenic factors and is frequently observed in conjunction with weaken Qi in both the spleen and kidney systems.¹² The treatment medication used in this study, TZD, is based on TCM theory and extensive clinical experience. TZD comprises Huangqi (Radix Astragali Mongolici), Xinyi (Flos Magnoliae Biondii Immaturus), Cangerzi (Fructus Xanthii), Wumei (Fructus Mume), Chantui (Periostracum Cryptotympanae), etc. These herbs collectively function to tonify lung Qi and dredge the nasal orifice.

As recorded in the Pharmacopoeia of the People’s Republic of China, both Xinyi (Flos Magnoliae Biondii Immaturus) and Cangerzi (Fructus Xanthii) can clear the nasal orifices. Xinyi (Flos Magnoliae Biondii Immaturus) focuses on dispelling wind and coldness whereas Cangerzi (Fructus Xanthii) dispels wind and dampness. Huangqi (Radix Astragali Mongolici) has been proved effective in enhancing lung qi and spleen Qi,²² thus it has a millennia-long history of utilization in TCM.²³ Furthermore, Chantui (Periostracum Cryptotympanae) dispels wind, relieves itching, while Wumei (Fructus Mume) can restrain the lungs, produce water, and quench thirst. Modern pharmacological studies have also confirmed that mume fructus and cicadae periostracum black have an antiallergic effect. In addition, a mouse study of TZD showed that TZD could control allergy by reducing OVA-specific IgE and histamine release. In nasal tissue, TZD decreased nasal rubbing and sneezing, reduced AR-induced damage to the nasal mucosa, clearly ameliorating nasal symptoms.¹¹ TZD and TZD’s main components have been shown to relieve major symptoms of allergic rhinitis such as nasal congestion, nasal itching, and eye itching.

Modern pharmacological studies have confirmed that the anti-allergic effect of active ingredients of TZD including mume fructus and cicadae periostracum black. The glucocorticoids contained in rhizome or licorice roots are also likely to have anti-inflammatory and anti-allergic effects.²³ It should still be noted that while pharmacological studies may uncover certain mechanisms of TZD’s respective components, the rationale behind the selection of herbs for TZD is still based on TCM theory, as recorded in the pharmacopoeia of the People’s Republic of China. Results in the clinical trial should be seen as a success worth understanding from both pharmacological and TCM achievement.

This study uses a randomized, placebo-controlled, double-blind design to explore the effects of TZD in AR patients, providing solid preliminary evidence for the safety and efficacy of TZD to treat SAR. The trial’s relatively short time frame also seeks to challenge the norm that TCM intervention can only be effective over a long treatment period, exhibiting promising results at both the 7-d and 14-d mark. It remains true, however, that our study only includes patients in Beijing, with largely subjective outcome measures, albeit controlled for with a placebo group. The retrospective questionnaire, especially the specific symptom score, may also have different degrees of bias. A larger sample size, a longer follow-up period, and/or the use of objective outcome measures would certainly bring a wider variety of evidence to the table.

Nevertheless, this study suggests that even two weeks of TZD may be an effective and safe treatment option for patients with SAR and spring pollen allergy, it significantly relieved their nasal and eye symptoms while also improved their quality of life.

5. ACKNOWLEDGEMENTS

We thank ZHANG Yuan from the Department of Allergy at Beijing TongRen Hospital, Capital Medical University, Beijing, China. We also thank the members of the data and safety monitoring committee for their contributions to the study.

Funding Statement

Supported by the Fundamental Research Funds for the Central Universities (No. 2023-JYB-JBZD-009); High level Key Discipline of National Administration of Traditional Chinese Medicine-Traditional Chinese Constitutional Medicine (No. zyyzdxk-2023251); General program of National Natural Science Foundation of China: Study on the Mechanism of "the Simultaneous Prevention of Different Diseases" of Allergic Constitution Regulating Formula based on DNA Trap Mediated Eosinophil-Derived Dendritic Cells Cell Crosstalk (No. 82174243); General Project of Beijing Natural Science Foundation: Study on the Mechanism of Guominkang for Treating Allergic Rhinitis through Regulating Body Constitution based on Vacuolating Cytotoxin A-mediated Eosinophil-derived Dendritic Cell Cell immune microenvironment (No. 7242227)