Effect of Omega-3 Fatty Acids on TH1/TH2 Polarization in Individuals with High Exposure To Particulate Matter ≤ 2.5 μm (PM2.5): A Randomized, Double-Blind, Placebo-Controlled Clinical Study

Abstract

Background: Long-term exposure to high concentrations of PM2.5 may cause immune system dysfunction and damage to the respiratory and cardiovascular systems. PM2.5 may cause CD4 + T helper cells to polarize toward TH1 or TH2 cell types, which may be associated with the onset and progression of many human diseases. Recent studies have shown that omega-3 fatty acids can regulate human immune function and reduce physiological damage caused by air pollution; however, only limited research has examined the therapeutic effects of omega-3 fatty acids on subjects with high exposure to PM2.5 in mass transit systems such as subways.

Methods: This study was designed as a prospective, randomized, double-blinded (to participants and researchers), placebo-controlled trial. The research plan is to recruit 120 qualified volunteers in the Chengdu Metro Station. All participants will receive omega-3 fatty acids or placebo for 8 weeks. The primary outcomes will be changes in the TH1/TH2 cell polarization index and changes in serum cytokine concentrations. Secondary outcomes will be changes in early indicators of atherosclerosis, pulmonary function, COOP/WONCA charts, and scores on the Short Form 36 Health Survey for quality of life. Results will be analyzed to evaluate differences in clinical efficacy between the two groups. A six-month follow-up period will be used to assess the long-term value of omega-3 fatty acids for respiratory and cardiovascular disease end-points.

Disscussion: We will explore the characteristics of TH1/TH2 cell polarization index in a population with high exposure to PM2.5. Omega-3 fatty acids and placebo will be compared in many ways to test the effect on people exposed to PM2.5 subway stations. This study is expected to provide reliable evidence to support the promotion of omega-3 fatty acids in clinical practice to protect individuals who are highly exposed to PM2.5.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2000038065). Registered on September 9, 2020.

Background

With the rapid development of urbanization and industrialization in many countries, air pollution has become an important factor that negatively affects the health of residents in these countries [1] [2] [3] [4]. In fact, air pollution has been identified as the cause of death for ~ 2 million people worldwide [5]. Particulate matter (PM), one of the main components of polluted air, is chemically complex, and may contain biological compounds, organic compounds and metals [5]. Studies have found that the composition of PM changes with time and space [6]. PM2.5 is a class of fine particulate matter with a diameter of < 2.5 microns. Unlike coarse PM, fine PM may reach the terminal bronchioles and alveoli of the lungs, causing oxidative stress, oxidative damage and inflammatory reactions in epithelial cells, as well as persistent adverse effects to the human body [7] [8] [9] [10].

The subway is a public transportation system widely used in many major cities throughout the world. As a relatively enclosed space, the PM2.5 concentration inside the subway system is several times higher than that on the street surface above [11]. PM2.5 in the subway is generated by friction between the wheels and rails, wear on the electric rails and overhead lines, electric current collectors and arcs. PM2.5 is rich in metal elements, including iron, manganese, chromium (from rails/wheels), barium (from brakes) and copper (from electrical components) [12] [13]. Any PM2.5 that settles on the subway floor will become re-suspended in the air due to train and passenger movements, which result in a continuous circulation of PM2.5 within the subway system. Subway workers often experience long-term occupational exposure to high concentrations of PM2.5, which may lead to adverse health effects.

Located in southwestern China, Chengdu is a modern metropolis with a total population of more than 16 million. The Chengdu Metro, which has been in operation for more than 10 years, currently has 8 lines, with a total length of 358.235 kilometers and 215 stations. In Chengdu, more than 1.4 billion commuters ride the subway each year (the Chengdu Metro Line Map is shown in Additional file 1). Previous studies have shown that short-term exposure to PM2.5 in subway systems may cause harm to humans [14]; however, few clinical studies have examined the effects of long-term exposure to PM2.5 among subway workers. To our knowledge, previous studies have mainly focused on physiological damage to humans caused by outdoor air pollution. Studies on subway employees exposed to PM2.5 are very rare. One study in China showed that the concentration of PM2.5 in the Chengdu subway was significantly higher than PM2.5 concentrations detected on city streets [15]. As the number of employees in the Chengdu subway system continues to increase, research is needed to assess potential harms that may result from PM2.5 exposure.

Omega-3 polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), have been shown to produce a variety of beneficial effects on human health [16]. A large number of epidemiological studies and clinical trials have shown that consumption of omega-3 fatty acids may have beneficial effects by reducing inflammation and regulating the function of macrophages, neutrophils, T cells and B cells [17] [18]. Studies have found that omega-3 fatty acids may regulate immune function and have beneficial health effects in clinical trials examining PM2.5 in indoor air pollution [19] [20] [21].

PM2.5 may damage the human body through systemic inflammation, changing the immune response and increasing oxidative stress [22]. As the initial deposition site of PM2.5, airway damage includes inflammation, bronchial remodeling and tissue fibrosis, which often appear in the early stages of disease [23]. PM2.5 exposure may disrupt the balance of TH1 and TH2 helper cells, cause the TH1/TH2 balance to shift in the direction of TH2 cells and increase the incidence of bronchial asthma and chronic inflammatory diseases [24] [25]. Although PM2.5 exposure is known to adversely affect TH1/TH2 polarization in humans, few clinical trials evaluating the impact of omega-3 fatty acids on TH1/TH2 polarization during PM2.5 exposure have been conducted. Therefore, this study was designed as a prospective, randomized, double-blinded (to participants and researchers), placebo-controlled trial to objectively evaluate the effects of omega-3 fatty acids on TH1/TH2 polarization in subway workers exposed to PM2.5.

Methods

Study design

This is a randomized, single-center, placebo-controlled, double-blinded clinical trial. This research protocol complies with the standard protocol project: Interventional Trial Recommendations (SPIRIT) Guidelines (Additional Document 2). The TH1/TH2 cell polarization index in the serum will be collected to determine the potential impact of people with high PM2.5 exposure. A flowchart of this trial procedure is shown in Fig. 1. This study protocol has been approved by the Chinese Ethics Committee of Registering Clinical Trials (Ethical Review No.: ChiECRCT20190343). Before randomization, all eligible participants will be asked to sign an informed consent (see Additional file 3).

Participant recruitment

We plan to recruit 120 participants from the Chengdu Metro Station. The recruitment methods used in this study include: (1) face-to-face communication, (2) bulletin boards, and (3) posters. We will post recruitment information at various subway stations in Chengdu, and broadcast the recruitment information on the subway broadcast. The members of the research team will receive uniform training after the project is launched, all of whom are medical staff with doctor certificates. The members of the research team will obtain the written consent of the participants, and their mobile phones will be kept open for 24 hours to communicate with the participants at any time. Participants can enter clinical trials only after the members of the research team confirm the qualifications of the participants on the spot and sign a written informed consent form. Eligible participants will be registered and randomly assigned to placebo or omega-3 fatty acids treatment. There is no anticipated harm and compensation for trial participation. All subject personal information and trial data will be treated as confidential, which will be recorded in the individual Case report forms (CRFs). These data will be uploaded in a database that only members of the research team can access. After the later data was completely uploaded, the subjects can enter the website (http://www.medresman.org.cn/login.aspx) to check. Enrollment will begin on November 1, 2020 and is expected to be completed by July 31, 2021. 

Sample size

G*Power 3.1 will be used to calculate the sample size necessary to have sufficient statistical power [26]. The sample size calculation will be based on a previous study of omega-3 fatty acids and their effects on up-regulating the TH1/TH2 ratio by ~32.5% [27]. The type I error is 0.05 and the power is 80%. Considering a dropout rate of 20%, we aim to recruit 120 subjects. The treatment group and the placebo group were assigned 60 participants each. Based on the grouping of our experiment, we will be divided into high exposure group and low exposure group according to PM2.5 exposure. In the high and low exposure groups, 30 subjects were treated with omega-3 fatty acids and placebo.

Selection criteria

Participants for this study will be recruited from long-term employees of the Chengdu subway system, who do not routinely wear professional anti-PM2.5 masks.

Inclusion criteria for the high PM2.5 exposure group include: 

1. Employees of the Chengdu subway system, regardless of gender, 20-65 years of age, who work in one of the station halls ≥3 times per week, ≥8 hours per day, and have been on the job continuously for ≥2 years; 
2. No obvious abnormalities detected by a physical examination in the past one year; 
3. Have not received hormones, antioxidant supplements (vitamin C, vitamin E) or non-steroidal anti-inflammatory drugs in the past three months; 
4. No history of surgery in the past three months; 
5. Willing and mentally competent to consent to participate in this experimental study and to sign an informed consent document.

Inclusion criteria for the low PM2.5 exposure group include: 

1. Employees of the Chengdu subway system who work in offices (with an air-conditioning device equipped with PM2.5 filters), regardless of gender, 20-65 years of age, who work in the office ≥3 times per week, ≥8 hours per day, and have been on the job continuously for ≥2 years; 
2. No obvious abnormalities detected by a physical examination in the past one year; 
3. Have not received hormones, antioxidant supplements (vitamin C, vitamin E), or non-steroidal anti-inflammatory drugs in the past three months; 
4. No history of surgery in the past three months; 
5. Willing and mentally competent to consent to participate in this experimental study and to sign an informed consent document.

Exclusion criteria

1. A long-term history of drug use;
2. Routine use of a PM2.5 respirator that complies with China's "PM2.5 Protective Masks" group standard (TAJ 1001-2015) during work; 
3. A history of smoking;
4. A history of bleeding;
5. An allergic reaction to flaxseed, fish and/or seafood;
6. A history of hepatitis, fatty liver, cirrhosis, cholecystitis or gallstones;
7. Currently pregnant or lactating;
8. Participation in another clinical trial within the past six months;
9. Inability to understand the intention of the experiment and inability to cooperate with the experimental procedure.

Randomization, allocation and concealment

Before the subjects agree to participate in this study, all qualified subjects who satisfy the inclusion and exclusion criteria will be given an information sheet describing the study and an opportunity to ask questions and clarify their concerns with the investigators. During the study, both the participants and the researchers will be blinded to the grouping information for each subject based on PM2.5 exposure level. BMISPSSStatistics24.0 software will generate 120 random numbers, and PM2.5 high-exposure group and PM2.5 low-exposure group will each allocate 60 random numbers. The researcher in charge of blinding will use two opaque envelopes to seal the random numbers, and will carefully check whether the serial numbers and drug numbers on the cover and letterhead are consistent with the labels on the drug packaging. Each subject will be provided with a corresponding emergency envelope. If the subject has a serious adverse event during the trial, the researcher will open the envelope after documenting the adverse event to break the blinding so that the subject can receive proper treatment.

Intervention

We plan to recruit 120 subjects who will be automatically divided into two groups based on their PM2.5 exposure level in the work environment: high PM2.5 exposure group (n=60) and low PM2.5 exposure group (n=60). In the high-exposure group, 30 people will receive omega-3 fatty acid treatment and the other 30 subjects will receive placebo treatment. Participants in the low-exposure group will receive an identical treatment regimen. 

1. Intervention group: Participants will receive treatment from the same batch of omega-3 fatty acids (1200 mg/capsule) provided by Kirkland, Canada. Participants will take two capsules every morning for eight weeks, and will be followed for 24 weeks after the trial. The omega-3 fatty acid capsules will be stored in a dry environment at room temperature.
2. Placebo group: Participants will receive placebo treatment, containing soybean oil as the main ingredient, which has been produced by the Placebo Experimental Center of the School of Pharmacy, Chengdu University of Traditional Chinese Medicine. The physical appearance and weight of the placebo will be the same as the omega-3 fatty acid capsules, and the administration methods, experimental period and storage methods will be identical to those in the intervention group.
3. The capsules for the intervention group and the placebo group will be packaged in the same box. Each box will contain eight weeks of drug dosage and will include the name of the subject, dosage, consumption schedule, description of storage conditions and expiration date. "Experiment only" will be highlighted in a prominent position on the box. We have selected soybean oil as the placebo (comparison) agent because it is commonly used in daily cooking, its physical properties are similar to omega-3 fatty acids and it has no obvious effects on TH1/TH2 polarization [28].
4. The drug to be used in this project is a nutritional supplement with controllable safety risks. the participant may do so if he/she has no adverse events or side effects. However, if the subject has diarrhea or nausea, their participation in the trial may be suspended and the adverse event will be reported to the research team. Due to the special nature of omega-3 fatty acids, we will prohibit participants from using antioxidant supplements, such as vitamin E, during the trial. Medications used by participants to treat other diseases will not be curtailed or changed. If omega-3 fatty acids are beneficial to subjects with high PM2.5 exposure, we will put the control subjects on the "waiting list", that is, after the trial, the control subjects will also be provided with omega-3 fatty acids for 8 weeks free of charge.

Data and sample collection

We will use the Chinese Clinical Research Public Management Platform (Res Man) to collect and manage the data. The experimental data can only be accessed and manipulated by the research team. 

The person in charge of the project will have access to the real-time data, but cannot make any changes to the data.

All data collectors will receive uniform training to ensure that data collected through questionnaires will have high quality and consistency. The Short Form Health Survey 36 (SF-36) [29], designed to assess quality of life through a comprehensive assessment of physical, mental and social components and COOP/WONCA charts will be completed at baseline, immediately after the final treatment(T1) and then at 12 weeks(T2)and 24 weeks(T3) after the final treatment. A pulmonologist will collect data on pulmonary function from all subjects to ensure consistency prior to and following the final treatment, as well as 24 weeks after the final treatment. We also will examine the follow-up records for each patient regarding respiratory and cardiovascular diseases at 12 weeks and 24 weeks following treatment. The time frame for data collection and assessments is shown in Table 1(the SPIRIT figure).

The number of TH1 and TH2 cells in the peripheral blood of subjects and the TH1/TH2 ratio will be measured at the time of enrollment (baseline) and again following treatment. Similarly, we will determine the TH1/TH2 polarization state, including the concentrations of serum interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-12 (IL-12), interleukin-6 (IL-6), interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1), as well as liver and renal function to assess drug safety, at baseline and following treatment.

The concentrations of TH1 and TH2 cells in the peripheral blood immune cell population will be detected by flow cytometry using a CytoFLEX Flow Cytometer (Beckman Coulter, Brea, California, USA). Serum IFN-γ, IL-4, IL-12, IL-6, IL-8 and ICAM-1 levels will be measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Liver and renal function will be assessed in the Laboratory of Hospital of Chengdu University of Traditional Chinese Medicine. The blood products of all subjects will be destroyed uniformly after the end of the study.

Primary outcome measureOutcome measures

We will evaluate the concentrations of TH1 and TH2 cells in peripheral blood and the TH1/TH2 polarization state (IFN-γ, IL-4, IL-12 and IL-6) prior to and following treatment, and calculate the TH1/TH2 ratio using the IFN-γ/IL-4 balance index. We will examine differences in these indicators between the treatment and placebo groups.

Secondary outcome measures

1. A pulmonary function test will be performed to evaluate the impact of PM2.5 on lung function in each subject.
2. Early indicators of atherosclerosis, including IL-8 and ICAM-1, will be measured.
3. The SF-36 questionnaire will be used to assess the health status of each subject and to generate a COOP/WONCA chart. The quality of life will be summarized for eight aspects: physical functioning, physical role functioning, physical pain, general health, vitality, social functioning, emotional health and mental health.
4. Safety and adverse reactions to drug treatment will be monitored.

Adverse events’ reporting and safety monitoring

The omega-3 fatty acids used in the project are a nutritional supplement with controllable safety risks. The Chinese Ethics Committee of Registering Clinical Trials (Ethical Review No.: ChiECRCT20190343) has approved this study. If the subject has any adverse events related to this study (such as diarrhea or nausea), it will be reported to the research team and recorded in the CRF. The project supervisor will also collect adverse events in a timely manner and decide on follow-up treatment (including close observation, additional medical management, or early termination).

Data management and monitoring

Data collection and monitoring will be managed by a dedicated Data and Security Monitoring Board (DSMB). The DSMB will be composed of a deputy chief physician from the respiratory department, a junior Chinese medicine practitioner and a statistician. DSMB members will provide appropriate recommendations on the safety and completeness of all procedures during the clinical trial. All completed questionnaires and laboratory results will be stored in a locked cabinet. The data will only be accessible to the researchers. Two data entry clerks will enter all data into an electronic database at the same time. The electronic database will be maintained as a password-protected file.

Statistical methods

IBM SPSS Statistics V.25 software will be used for statistical analysis of the data collected in this study. Subjects who withdrew from the experiment but received at least one treatment will still be included in the intention-to-treat analysis. We will use various attribution methods to conduct sensitivity analysis to test whether the results are reliable for different assumptions about missing data. Demographic and baseline data will be tabulated and evaluated using analysis of variance (ANOVA) or the χ2 test. Analysis of variance was performed on categorical variables, and Pearson χ2 test was performed on continuous variables. 95% CI will be used for continuous variables. In this study, all statistical tests will be two-way, and P value <0.05 is considered valid.

Discussion

In recent years, damage to the human body caused by PM2.5 has been a research topic of great interest, and many scientists have been looking for effective intervention methods. Currently, a standard PM2.5 protective mask is the most convenient method for individuals; however, wearing a PM2.5 protective mask for an extended period of time during work or physical activity often causes discomfort. People may wear PM2.5 masks incorrectly, and improper fit during activities may reduce their effectiveness [30]. 

PM2.5 exposure is one of several important factors that affect the differentiation status of CD4 + T helper cells [31] [32]. Studies have shown that the combined action of multiple cytokines leads to the polarization of TH1/TH2. IL-12 and IFN-γ stimulate naive CD4 + T cells to increase the expression of T-bet and STAT4 and to differentiate into TH1 cells. Similarly, IL-4 stimulates naive CD4 + T cells to increase the expression of STAT6 and GATA3 and to differentiate into TH2 cells [33]. TH1/TH2 polarization is involved in the progression of many diseases [33]. In this study, we will use the polarization state of TH1/TH2 as the main variable to examine the concentration of the primary cytokines in TH1 and TH2 immune cells to provide an objective explanation for the polarization of TH1/TH2 by omega-3 fatty acids. We will detect changes in ICAM-1 and IL-8 [34] [35], which have been identified as early indicators of atherosclerosis and vascular endothelial damage caused by PM2.5, to explain physiological mechanisms of PM2.5 damage to the vascular endothelium.

Omega-3 fatty acids, when used as nutritional supplements, have been shown to have beneficial effects on human health; however, research on the efficacy of omega-3 fatty acids on adverse health effects attributable to PM2.5 exposure has been concentrated on animal models. We will utilize employees of the Chengdu Metro system in China, who work mainly indoors, as research subjects for this study. Due to the rapid development of the Chengdu Metro in recent years, it is estimated that by the end of 2020, the total mileage of Chengdu Metro will rank fourth in China. Tens of thousands of subway workers have been exposed to PM2.5 for many years, and the disposable medical masks commonly worn by subway employees do not effectively protect employees from PM2.5 exposure. Few relevant data sets have been produced that examined changes in human biological markers associated with long-term exposure to PM2.5. Previous studies have focused on physiological damage caused by outdoor exposure to PM2.5, but in this experiment, we will examine PM2.5 exposure to employees inside the subway system. The relatively stable exposure environment of the enclosed subway system will improve the objectivity of the conclusions from this experiment. 

Trial registration

The trial was pre-registered at the China Clinical Trials Registry on September 9, 2020 under the registration number ChiCTR2000038065. See http://www.chictr.org.cn/index.aspx

Trial status

Recruitment began in November 1, 2020, and approximate date of completion is July 31, 2021. This protocol is based on protocol version 2.0 dated October 31, 2020.

Modification of the Protocol

Any changes to the study will be agreed by the project leader and the supervisor, and the project team members and the ethics committee will be notified before the changes can be made. 

Abbreviations

Declarations

Acknowledgements 

We would like to thank teacher Du Liang of Sichuan Huaxi Hospital for his theoretical guidance on this subject.

Author contributions 

XW contributed to study concept and design. XW and SL wrote the first draft of the protocol manuscript. FW and YW supervised the process. YW and CP revised the manuscript after feedback from all authors. DH and SS coordinate the conducting of this study. All authors reviewed the manuscript and approved the final version of the manuscript.

Funding 

This study is supported by the Key R&D Program of Sichuan Provincial Department of Science and Technology (Number 2020YFS0312, 19ZDYF0611) and Sichuan Province Health Research Project (Number 20PJ160). Funding agency does not have any role in the study design, data collection, data analysis or publication of results. Sponsor contact name: Zhenxing Wang, Address: No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, P.R. China. Telephone: +8619108201441, Email: [email protected]. The sponsor played no part in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.

Availability of data and materials

Data sharing is not applicable to this article as no datasets are reported. The full protocol of this study will be provided by the corresponding author. The paper reporting the research results will disclose the availability of the data sets generated in the research. Upon reasonable request, the author can access the complete agreement and model consent form.

Ethics approval and consent to participate

The Chinese Ethics Committee of Registering Clinical Trials reviewed this study protocol and gave its approval and consent on 31 October 2020 (Ethical Review No.: ChiECRCT20190343). We ensure that written informed consent will be obtained from all study participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Voluntary Subject Statement:

I have learned about the requirements of the clinical study in detail and the potential adverse reactions associated with it. I voluntarily participate in this clinical study, receive treatment on time, and fill out the relevant health questionnaire in accordance with the requirements of the research program. If adverse reactions occur, I will report to the doctor promptly. At the same time I know that the doctor will give positive response for my possible adverse reactions. I am also entitled to withdraw from the study at any time for any reason. However, if there are no special circumstances, I will cooperate with the doctor to complete the clinical study. My participation and the personal data in the trial are confidential. I agree with my doctor, the relevant regulatory authorities, and the ethics committee to review my information as required.

I (signature)      relative (signature)                 (Relationship)        

Date:      D       M      Y 

Doctor's declaration 

I have fully explained the requirements of the clinical study in detail and the potential adverse reactions to the above participant/relative, and answered their questions. To the best of my knowledge, the participant/relative has been informed adequately and has consented. 

Doctor’s signature:                                Date:       D      M      Y  

In the event of inconsistency or discrepancy between the Chinese version and the English version, the Chinese language version shall prevail.

Ethical approval document

Ethics Review Report of China Registered Clinical Trial Ethics Committee

Research topic: Clinical study of Th1/Th2 balance drift and Omega-3 fatty acid intervention in people with high PM2.5 exposure in Chengdu subway station hall

Applicant reviewer: Shuiqin Li 

Tel: 18628912226 

Email: [email protected] 

Applicant review unit: Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Ethics review number: ChiECRCT20190343

This ethics committee is in accordance with the "Measures for the Ethical Review of Biomedical Research Involving People (Trial)" by the Health and Family Planning Commission of the People's Republic of China (formerly the Ministry of Health) (Health Science Education Fa [2007] No. 17), the Declaration of Helsinki v.08 and the "International Ethical Guidelines for Human Biomedical Research" on the clinical trial submitted by Deputy Chief Physician Shuiqin Li of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine for ethical review "The Th1/Th2 balance drift and Omega-3 fatty acid intervention in people with high PM2.5 exposure in Chengdu subway station hall "Clinical Research" to be reviewed, and the report is as follows:

The review experts of this ethics committee believe that the safety risk of the study is low for the test participants; the management and control measures of the research team for potential adverse reactions meet the requirements of GCP; the informed consent process is reasonable; the trial adopts a randomized controlled design and meets the research purpose.

Therefore, the research is in line with medical research ethics and agreed to be implemented according to the protocol (version number 2.0).

Funding document

Declaration number：20ZDYF1190  Plan number：2020YFS0312  Secret level

Task contract of Science and Technology Plan Project in Sichuan Province

Type of plan: key R & D projects

Project name：Nasal microflora-intestinal microflora-host interaction and the regulation mechanism of Ganduqing: a randomized, double-blind, placebo-controlled clinical study in Chengdu PM2.5 high-exposure population

Applicant: Chengdu University of traditional Chinese Medicine

Project leader: Zhenxing Wang

Contact number：028-86691467

Recommended unit：Department of Education of Sichuan Province

Project funding: 20 ($30,000)

Project start and end date：2020.01.01-2021.12.31

 Declaration number：19ZDYF Plan number：2019YFS0083   Secret level

Task contract of Science and Technology Plan Project in Sichuan Province

Type of plan: key R & D projects

Project name：Nasal microflora-intestinal microflora-host interaction and the regulation mechanism of Ganduqing: a randomized, double-blind, placebo-controlled clinical study in Chengdu PM2.5 high-exposure population

Applicant: Chengdu University of traditional Chinese Medicine

Project leader: Fei Wang

Contact number：028-86691569

Recommended unit：Department of Education of Sichuan Province

Project funding: 50 ($76,000)

Project start and end date：2019.01.01-2021.12.31

Declaration number：20PJ160  Plan number：20PJ160   Secret level

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