
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39029033
MD-D-24-04071
00035
10.1097/MD.0000000000038904
3
6700
Research Article
Systematic Review and Meta-Analysis
Effectiveness of Bairui granules in the treatment of respiratory tract infections: A systematic review and meta-analysis
Chai Keyan MM lucky857446618@163.com
a
Wang Haojia PhD wanghaojia123@yeah.net
a
Guan Yueqin PhD guanyueqin@hkjhhy.com
b
Shi Rui MM sr1918sr1918@163.com
a
Stalin Antony PhD staanlin@gmail.com
c
Zhai Yiyan MM yiyanouba@163.com
a
Zhou Jiying MM 19510166800@163.com
a
Qiao Chuanqi MM 2105376746@qq.com
a
Yang Siyun MM YYgoodluck123456@163.com
a
Li Jiaqi MM L18235778875@163.com
a
Zhang Xiaomeng PhD zhangxm0320@163.com
a
Wu Jiarui PhD a*
a Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
b Jiuhua Huayuan Pharmaceutical Co., Ltd, Anhui, Chuzhou, China
c Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China.
* Correspondence: Jiarui Wu, Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China (e-mail: exogamy@163.com).
19 7 2024
19 7 2024
103 29 e3890416 4 2024
02 6 2024
20 6 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Background:

Respiratory tract infections (RTIs) are characterized by a high mortality rate and clinical incidence. Bairui granules (BG), which employ a method of heat elimination and detoxification, have demonstrated benefits in the treatment of infectious respiratory diseases.

Methods:

A computerized search of 6 databases was conducted to identify randomized controlled trials (RCTs) relevant to the treatment of RTIs with BG up to November 30, 2023. Two researchers independently conducted data extraction, risk of bias assessment, and grading analysis. To evaluate the stability of the results, trial sequential analysis was employed.

Results:

This meta-analysis included 31 RCTs with a total of 4073 patients and demonstrated that the use of BG in the treatment of RTIs was associated with enhanced treatment efficacy (relative risk = 1.19, 95% credible interval: 1.16–1.22, P < .001). It also indicated a faster resolution of symptoms including pulmonary rales, cough, and fever, as well as a reduction in serological index factors, compared to the use of Western medicine treatment (WT) alone. Additionally, the duration of hospitalization for patients was significantly reduced (relative risk = −1.36, 95% credible interval: −1.55 to −1.17, P < .001). Trial sequential analysis confirmed the stability and conclusive evidence of the study results. The efficacy of treating RTIs with BG, either alone or in combination with WT, was found to be superior to WT alone. However, further high-quality RCTs are necessary to validate these outcomes.

Conclusion:

The effectiveness of treating RTIs using BG alone or in combination with WT was determined to be superior to using WT alone, with no serious adverse effects observed. However, additional RCTs are essential to further confirm the findings of this study.

Bairui granules
meta-analysis
respiratory tract infections
Traditional Chinese Medicine
treatment efficacy
OPEN-ACCESSTRUE
SDCT
==== Body
pmc1. Introduction

Respiratory tract infections (RTIs) are the primary cause of mortality due to their rapid onset, severe symptoms, and numerous complications.[1,2] RTIs are particularly dangerous for children, the elderly, and individuals with weakened immune systems, RTIs can be divided into upper respiratory tract infections (URTIs) and lower respiratory tract infections. URTIs mainly affect the nasal cavity, throat, and surrounding areas. Based on their clinical features, they can be categorized into conditions such as the common cold, herpetic pharyngitis, pharyngitis, and pharyngeal conjunctivitis. Lower respiratory tract infections, involve infections below the pharynx, affecting the trachea, bronchi, and lungs; these include tracheitis, bronchitis, and pneumonia.[3] The main clinical symptoms include fever, cough, sputum production, sore throat, runny nose, wheezing, and pulmonary rales.

Currently, conventional Western medicine primarily focuses on antibiotics, anti-inflammatory, and anti-infective treatments. However, the effectiveness of these treatments is generally moderate, and there is a risk of recurrence. Frequent use of these medications can also lead to drug resistance. Research has shown that combining Traditional Chinese Medicine (TCM) with WT is more effective in treating URTIs in children.[4,5] Simultaneously, comprehensive diagnostic and therapeutic approaches that integrate both WT and TCM have emerged as a prevailing trend in clinical interventions for RTIs.[6]

BG is a TCM known for its efficacy in clearing heat, reducing inflammation, and relieving cough, while also promoting the excretion of phlegm.[7,8] It is formulated through modern processes using extracts from Thesium chinense Turcz.[9] The main active components, flavonoids, are noted for their anti-inflammatory and antibacterial effects.[10] Additionally, BG possesses antiviral properties, strengthens the immune system, and offers antipyretic and analgesic effects. It is commonly used in treating respiratory system disorders.[11] Although there is a substantial volume of clinical research literature in domestic databases on the treatment of RTIs with BG, there is a scarcity of studies employing evidence-based medicine methodologies in this area. This study aims to systematically review the current randomized controlled trials (RCTs) focusing on the application of BG in the treatment of RTIs. It employs a combination of meta-analysis and computational technique to thoroughly analyze and assess the gathered RCTs. The goal is to elucidate the efficacy and safety of BG in treating RTIs and to provide novel evidence grounded in clinical medicine, thereby guiding the accurate use of medication for patients.

2. Methods

The current study adhered to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The protocol number that we registered on the PROSPERO is CRD42024523535.

2.1. Literature search strategy

RCTs focusing on the treatment of RTIs with BG were sourced from the following databases: China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, SinoMed, PubMed, and Embase. The search spanned from the inception of each database to November 30, 2023. The search strategy involved a combination of subject terms and free text terms. China National Knowledge Infrastructure was used as an example to represent Chinese databases, with a detailed search strategy provided in Appendix 1, Supplemental Digital Content, http://links.lww.com/MD/N233.

2.2. Inclusion and exclusion criteria

2.2.1. Participants

We included articles that enrolled patients diagnosed with RTIs, such as URTIs, bronchitis, and pneumonia, confirmed by diagnostic criteria from both Chinese and Western medicine. Consent was obtained from the patients or their family members. Patients with significant cardiac, renal, or hepatic abnormalities, those with concomitant mental disorders, and those with other pulmonary diseases were excluded.

2.2.2. Interventions and comparisons

We included RCTs that described patients in the control groups received conventional WT for symptomatic treatment, including Cefixime granules, Budesonide, Terbutaline, Erythromycin, Azithromycin, and Ribavirin. The trial groups received either BG alone or BG in combination with the control group’s medications.

2.2.3. Outcome assessments

The primary outcome was treatment effect. The effectiveness of the treatment was categorized into 3 groups: obvious effect/cure: the main clinical symptoms and signs of the patients essentially disappeared, and the functional indicators returned to normal. Partial effect/improvement: there was significant improvement in patients’ clinical symptoms, signs, and functional indicators compared to before treatment. Ineffectiveness: there was no significant improvement in clinical symptoms and functional indicators. Treatment efficiency was calculated as the percentage of cases with a cure or improvement relative to the total number of cases according to the following formula: treatment efficiency = (the number of cure cases + the number of improvement cases)/total number of cases × 100%.

The secondary outcomes were time to disappearance of symptoms, including wheezing, fever, and cough; changes in pulmonary function indicators, such as FEV1/FVC; changes in serological markers, including C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α); and duration of hospitalization.

2.2.4. Type of studies

We included RCTs employing BG for treating RTIs. This encompassed journal articles, dissertations, and conference papers, where the literature was cited as “randomly.” Publications were included without language restrictions, regardless of the use of allocation concealment and blinding. Studies were excluded if they reported severe allergic reactions or contraindications to the treatment drugs used, if other antiviral or anti-infective treatments were administered before enrollment, or if the full text was not available. Additionally, literature with missing data or significant errors, and publications related to animal experiments and nonclinical trials were excluded.

2.3. Literature screening and data extraction

Two researchers (Keyan Chai and Haojia Wang) independently conducted literature screening and data extraction. The management of literature was facilitated using NoteExpress software (Beijing Aegean Music Technology Co., Ltd., Beijing, China). In instances where consensus could not be achieved, a resolution was reached through discussion or by seeking guidance from a third party (Jiarui Wu). Following the elimination of duplicate literature, a thorough review of titles and abstracts was conducted to identify articles that did not conform to the inclusion criteria. The literature meeting the specified criteria underwent a comprehensive reading, and pertinent data were extracted. Data compilation was performed using Excel software.

The extracted information included the following details: the name of the primary author and the publication year; distinct particulars for both the trial and control groups, encompassing case numbers, gender distribution, age (including age range and mean age), specific disease, course of the disease, intervention, treatment duration; and outcome indicators data.

2.4. Risk of bias assessment and GRADE evaluation

The assessment of potential bias in the included literature was conducted using the Cochrane Risk of Bias Tool 2.0 (RoB2) for RCTs.[12] This evaluation was carried out collaboratively by Keyan Chai and Haojia Wang. In cases where discrepancies arose between the 2 reviewers regarding the evaluated risk of bias, a third reviewer (Jiarui Wu) facilitated consensus. The risk of bias evaluation included the randomization process, deviations from planned interventions, missing outcome data, outcome measurement, and the selection of reported outcomes. The studies were categorized as low, some concerns, and high risk of bias.[13] Using GRADE profiler 3.6,[14] we assessed the quality of evidence, categorizing it into 4 levels: high, moderate, low, and very low. The evaluation encompassed 5 key aspects: risk of bias, inconsistency, indirectness, imprecision, and publication bias.

2.5. Trial sequential analysis (TSA)

To assess the credibility of the statistical results and the trial sequential monitoring boundaries, TSA software version 0.9 beta (Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark (http://www.ctu.dk/tsa)) was employed.[15,16] The two-sided Type I error probability α, Type II error probability β, and the conventional critical value (Z) were set to 0.05, 0.2, and 1.96, respectively. The sample size represents the required information size (RIS).[17,18]

2.6. Statistical analysis of the data

The analysis of the data was conducted using RevMan 5.3 software (The Nordic Cochrane Centre, Copenhagen, Denmark). For dichotomous variables, the relative risk (RR) was used as the indicator, and for continuous variables, mean difference statistics were employed, accompanied by the calculation of 95% confidence intervals (95%CI). Heterogeneity was evaluated through the Q-test and the I2-test. In cases where P > .1 and I2 < 50%, a fixed-effects model was employed.[19] To gauge the robustness of the findings, a sensitivity analysis was carried out using the single exclusion method in Stata 15 software (Stata Corp., College Station, TX). Publication bias was assessed by constructing a funnel plot with Stata 15 software; the presence of asymmetry or missing corners in the funnel plot indicated potential publication bias. Additionally, we performed Egger test to further assess bias and used the trim-and-fill method to correct the funnel plot.

3. Results

3.1. Literature search and screening results

A total of 65 original publications were identified, and 39 articles underwent a comprehensive full-text review. Ultimately, 31 RCTs were deemed eligible for inclusion, all of which were Chinese literature with publication years ranging from 2013 to 2023. The literature screening process was illustrated in Figure 1.

Figure 1. Literature screening process.

3.2. Basic characteristics of the included studies

A comprehensive total of 31 investigations, encompassing 4073 patients, were included in this study. Among these, 2050 patients constituted the trial group, while 2023 patients comprised the control group. Patient ages ranged from 4 months to 82 years, predominantly children, except for elderly individuals with chronic conditions. The included studies exhibited varying sample sizes, ranging from a minimum of 45 cases to a maximum of 297 cases. Further details on the characteristics of the included literature can be found in Table 1.

Table 1 Characteristics of the included literature.

Study ID	Number of cases (T/C)	Gender (M/F)	Age range	Mean age in years (T/C)	Specific disease	Disease progression	Intervention in the control group	Intervention in the trial group	Treatment duration (d)	Outcome measures	
Deng Liping 2022[20]	60/60	74/46	63–82	68.64 ± 3.78/68.42 ± 3.85	Chronic Obstructive Pulmonary Disease	6–15.2 years	Basic treatment of western medicine	Basic treatment of western medicine + Bairui granule 15 g/d	14	①③	
Feng Yecheng 2020[21]	43/43	44/42	1–12	6.13 ± 1.07/6.38 ± 1.26	Acute Bronchitis	1–10 d	Cefoxime particles 20~40mg/(kg•d)	Cefoxime particles 20~40mg/(kg•d) + Bairui granule 15g/d	7	①②④	
Guo Aili 2017[22]	42/42	46/38	5 months–2	1.14 ± 0.62/1.28 ± 0.44	Capillary bronchitis	1–5 d	Budesonide 0.5–1 mg and terbutaline (2.5–5 mg) × 2	Budesonide 0.5–1 mg and terbutaline (2.5–5 mg) × 2 + Bairui granule 7.5 g/d	7	①②	
He Jian 2020[23]	30/30	31/29	3–12	8.21 ± 3.12/8.69 ± 3.32	Whooping cough	6–33d	Erythromycin tablets 20–30 mg/(kg•d)	Erythromycin tablets 20~30mg/(kg•d) + Bairui granule 15g/d	14	①②④	
Huang Yingxiang 2021[24]	64/64	76/52	63–80	69.88 ± 4.75/71.34 ± 4.54	Chronic Obstructive Pulmonary Disease	6.4–15.2 years	Basic treatment of western medicine	Basic treatment of western medicine + Cefoperazone sodium sulbactam sodium 3g/d + Bairui granule 15g/d	7	①③	
Li Wen (Shi Hua) 2020[25]	57/56	50/63	5–10	7.42 ± 0.93/7.31 ± 0.88	Mycoplasma Pneumonia Infection Complicated with Cough Variant Asthma	2–10d	Azithromycin (10 mg/kg·d) (5 mg/(kg·d × 3) + Budesonide 2–4 mL/d	Azithromycin (10 mg/kg·d) (5 mg/(kg·d × 3)) + Budesonide 2–4 mL/d + Bairui granule 15 g/d	28	①②③	
Li Wen 2020[26]	49/48	55/42	5–14	8.71 ± 0.72/8.94 ± 0.83	Cough Variant Asthma	1–13 months	Azithromycin 10 mg/kg·d × 3 + Budesonide 1–2 mg/d	Azithromycin 10 mg/kg·d × 3 + Budesonide 1–2 mg/d + Bairui granule 7.5 g/d	56	①②③④	
Li Xiangjin 2018[27]	60/60	63/57	5 months–8	5 months–8/6 months~7	Herpangina	NR	Ribavirin 18 mg/d	Ribavirin 18 mg/d + Bairui granule 7.5–15 g/d	NR	①②	
Li Yanyan 2016[28]	50/50	60/40	2–12	6.8 ± 2.3/6.4 ± 2.2	Mycoplasma Pneumonia	NR	Erythromycin injection 20 mg/(kg·d) × 5 + Azithromycin	Erythromycin injection 20 mg/(kg·d) × 5 + Azithromycin + Bairui granule 7.5–15 g/d	7	①②	
Ma Wenxu 2015[29]	90/90	104/76	NR	5.8 ± 1.3/5.5 ± 1.0	Acute Upper Respiratory Tract Infection	≤7 d	Ribavirin 10 mg/(kg·d)	Ribavirin 10 mg/(kg·d) + Bairui granule 5–7.5 g/d	3	①②⑤	
Ma Yanwei 2021[30]	48/48	55/41	1–9	5.87 ± 1.65/5.16 ± 1.04	Acute Suppurative Otitis Media	NR	Ofloxacin otic solution	Ofloxacin otic solution + Bairui granule 15g/d	10	①	
Mai Zeying 2018[31]	140/122	153/109	6 months–8	2.51 ± 0.92/2.43 ± 0.88	Herpangina	NR	Ribavirin injection 5–10mg/(kg·d)	Bairui granule	5	①②	
Mai Zeying 2019[32]	56/56	66/46	1–8	4.5 ± 1.3/4.6 ± 1.2	Mycoplasma Pneumonia	NR	Azithromycin	Azithromycin + Bairui granule 5–7.5 g/d	5	①②	
Rao Lufei 2018[33]	35/35	36/34	2~7	4.71 ± 1.6/4.74 ± 1.5	Herpangina	<2 d	Ribavirin granules 10–15 mg/(kg·d)	Bairui granule 7.5–15 g/d	5	①②	
Ren Xuchao 2021[34]	45/45	49/41	3–6	5.32 ± 1.05/4.11 ± 1.12	Acute Suppurative Otitis Media	NR	Ofloxacin hydrochloride ear drops	Ofloxacin hydrochloride ear drops + Bairui granule 15 g/d	14	①	
Song Qiang 2023[35]	52/52	58/46	6 months–7	3.23 ± 0.25/3.69 ± 0.41	Herpangina	1–5 d	Ribavirin injection	Ribavirin injection + Bairui granule 15g/d	7	①②④⑤	
Sun Lu 2021[36]	68/68	80/56	5 months–11	6.82 ± 1.16/6.78 ± 1.24	Acute Bronchitis	≤7 d	Cephalosporin or Macrolide antibiotics	Cephalosporin or Macrolide antibiotics + Bairui granule 5–15 g/d	7	①②	
Tian Ying 2014[37]	23/22	24/21	6 months~7	2.5 ± 0.7/2.6 ± 0.8	Herpangina	1–3 d	Ribavirin 5–10 mg/(kg·d)	Ribavirin 5–10 mg/(kg·d) + Bairui granule 7.5–15 g/d	5	①②	
Wang Jiaxi 2018[38]	100/100	101/99	14–40	23.8/24.3	Acute Tonsillitis	NR	Amoxicillin and clavulanate potassium tablet 0.914 g/d	Amoxicillin and clavulanate potassium tablet 0.914 g/d + Bairui granule 15 g/d	5	①②	
Wang Weihua 2013[39]	100/100	164/136	NR	3.13 ± 2.50/3.26 ± 2.42/3.33 ± 2.29	Herpangina	1–5 d	Ribavirin granules 30 mg/(kg·d)	Bairui granule 15 g/d	5	①②	
Wei Yanmin 2015[40]	52/52	55/49	4 months–11	5.2 ± 1.3/5.6 ± 1.5	Acute Upper Respiratory Tract Infection	NR	Ribavirin injection	Ribavirin injection 10 mg/ kg·d + Bairui granule 5–7.5 g/d	6	①②	
Xu Bing 2023[41]	51/51	56/46	3–13	7.32 ± 1.05/7.28 ± 0.94	Acute Bronchitis	1–7 d	Ceftezole sodium 20–80 mg/(kg·d)	Ceftezole sodium 20–80 mg/(kg·d) + Bairui granule	7	①④	
Yan Silu 2023[42]	45/45	46/44	3–12	6.71 ± 2.03/6.77 ± 1.91	Purulent Tonsillitis	≤3 d	Amoxicillin sodium and clavulanate potassium 60 mg/(kg·d)	Amoxicillin sodium and clavulanate potassium 60mg/(kg·d) + Bairui granule 15 g/d	5	①②④	
Yang Huafei 2023[43]	60/60	55/65	2–14	6.18 ± 2.93/5.79 ± 1.88	Mycoplasma Pneumonia	3–10d	Azithromycin	Azithromycin + Bairui granule 7.5–15 g/d	11	①②④	
Ye Jinbin 2019[44]	68/68	73/63	1–10	4.9 ± 0.75/4.93 ± 0.85	Acute Suppurative Otitis Media	NR	Oxifloxacin ear drops	Ofloxacin hydrochloride ear drops + Bairui granule 15 g/d	7	①	
Zhao Peng 2019[45]	94/92	98/88	1–11	5.1 ± 2.6/4.8 ± 2.4	Acute Suppurative Otitis Media	NR	Oxifloxacin ear drops	Ofloxacin hydrochloride ear drops + Bairui granule 15 g/d	7–10	①	
Zheng Yunwei 2020[46]	73/72	85/65	40–70	62.8 ± 7.3/62.6 ± 7.2	Chronic bronchitis	≤3 d	Ambroxol hydrochloride 90 mg/d	Ambroxol hydrochloride 90 mg/d + Bairui granule 15 g/d	14	①②③④	
Zhong Jiaoxia 2022[47]	75/75	77/73	3–12	8.27 ± 0.75/8.53 ± 0.74	Acute Tonsillitis	1–48h	Cefprozil tablets 0.5 g/d	Cefprozil tablets 0.5 g/d + Bairui granule	6	①②④	
Zhou Yongkang 2023[48]	150/147	137/160	6 months–12	1.12 ± 0.73/1.11 ± 0.94	Severe pneumonia	1–15d	Hydrobromide ambroxol solution, Western medicine symptomatic treatment	Hydrobromide ambroxol solution, Western medicine symptomatic treatment + Bairui granule 5–15 g/d	7	①②⑤	
Zeng Yingying 2021[49]	90/90	91/89	6 months–7	3.32 ± 1.57/3.25 ± 1.62	Herpangina	3–7 d	Ribavirin injection 20–30 mg/(kg·d)	Ribavirin injection 20–30 mg/(kg·d) + Bairui granule 7.5–15 g/d	7	①②④⑤	
Wang Long 2017[50]	80/80	84/76	NR	1.5 ± 0.9/1.6 ± 1.0	Capillary Bronchitis	NR	Salbutamol 2.5 mg	Salbutamol 2.5 mg + Bairui granule 15 g/d	3–5 d	①②⑤	
Note: T, trial group; C, control group; M, male; F, female; NR, not reported; ①, treatment effect; ②, symptom resolution time; ③, changes in pulmonary function indicators; ④, alterations in serological markers; ⑤, hospitalization duration.

3.3. Quality assessment and GRADE analysis

Based on the RoB 2.0 criteria, among the studies incorporated in the analysis, 19 RCTs provided details on their randomization processes, resulting in their classification as low risk (61.3%). The remaining 12 studies (38.7%) lacked a description of the randomization process and were categorized as some concerns. All studies adhered to the defined intervention allocation without any deviations, leading to a classification of low risk in this aspect. Complete outcome data were reported in all studies (100%), and the outcomes were based on objective patient conditions, encompassing overall efficacy rates, pulmonary function indicators, and the time to resolution of clinical symptoms. All included studies demonstrated outcome indicators consistent with the pre-analysis, indicating a low risk of selective reporting bias. A summarized presentation of the risk of bias in the included studies was depicted in Figure 2.

Figure 2. Summary of the risk of bias assessment of the included RCTs. RCTs = randomized controlled trials.

The evidence level of each outcome indicator included in the meta-analysis was evaluated. The results showed that the overall efficacy, wheezing symptom relief time, disappearance of pulmonary rales subgroups, fever, cough, FEV1/FVC, C-reactive protein, TNF-α, and hospitalization time were of moderate-quality evidence. Other subgroups of diseases for the disappearance of pulmonary rales and other diseases subgroups of cough indicators were of low-quality evidence, while the disappearance of cough in the mycoplasma pneumoniae and acute upper respiratory tract infection subgroups was of high-quality evidence. Detailed information can be found in Table 2.

Table 2 GRADE evaluation results.

Outcomes	Relative effect
(95%CI)	No of participants
(studies)	Quality of the evidence
(GRADE)	
Overall effectiveness	RR 1.19
(1.16–1.22)	4073
(31 studies)	⊕⊕⊕⊝
moderate*,†,‡	
Wheezing disappearance time	The mean wheezing disappearance time in the intervention groups was
1.62 lower
(2.59 to 0.65 lower)	461
(4 studies)	⊕⊕⊕⊝
moderate	
Pulmonary rales disappearance time	The mean pulmonary rales disappearance time in the intervention groups was
1.81 lower
(2.25–1.38 lower)	1306
(10 studies)	⊕⊕⊝⊝
low§,∥	
Pulmonary rales disappearance time - mycoplasma pneumonia	The mean pulmonary rales disappearance time—mycoplasma pneumonia in the intervention groups was
3.17 lower
(3.56—2.78 lower)	332
(3 studies)	⊕⊕⊕⊝
moderate∥	
Pulmonary rales disappearance time - acute upper respiratory infection	The mean pulmonary rales disappearance time—acute upper respiratory infection in the intervention groups was
1.55 lower
(2.42—0.68 lower)	472
(4 studies)	⊕⊕⊕⊝
moderate∥	
Pulmonary rales disappearance time - other diseases	The mean pulmonary rales disappearance time—other diseases in the intervention groups was
1.06 lower
(1.19—0.93 lower)	502
(3 studies)	⊕⊕⊝⊝
low§	
Fever disappearance time	The mean fever disappearance time in the intervention groups was
1.32 lower
(1.65—1 lower)	2192
(17 studies)	⊕⊕⊕⊝
moderate∥	
Cough disappearance	The mean cough disappearance in the intervention groups was
1.77 lower
(2.23—1.3 lower)	1896
(15 studies)	⊕⊕⊕⊝
moderate∥	
Cough disappearance—acute bronchitis	The mean cough disappearance—acute bronchitis in the intervention groups was
1.58 lower
(2.25—0.92 lower)	324
(3 studies)	⊕⊕⊕⊝
moderate∥	
Cough disappearance—mycoplasma pneumonia	The mean cough disappearance—mycoplasma pneumonia in the intervention groups was
2.55 lower
(3.79—1.31 lower)	445
(4 studies)	⊕⊕⊕⊕
high	
Cough disappearance—bronchiolitis	The mean cough disappearance—bronchiolitis in the intervention groups was
1.58 lower
(2.51—0.65 lower)	244
(2 studies)	⊕⊕⊕⊝
moderate∥	
Cough disappearance—acute upper respiratory tract infection	The mean cough disappearance—acute upper respiratory tract infection in the intervention groups was
1.26 lower
(1.49—1.03 lower)	284
(2 studies)	⊕⊕⊕⊕
high	
Cough disappearance—other types	The mean cough disappearance—other types in the intervention groups was
1.49 lower
(3.12 lower—0.13 higher)	599
(4 studies)	⊕⊕⊝⊝
low§	
FEV1/FVC	The mean FEV1/FVC in the intervention groups was
4.09 higher
(0.45—7.72 higher)	475
(4 studies)	⊕⊕⊕⊝
moderate§,∥,¶	
C-reactive protein	The mean c-reactive protein in the intervention groups was
2.28 lower
(2.61–1.95 lower)	592
(6 studies)	⊕⊕⊕⊝
moderate§,¶	
Tumor necrosis factor-α	The mean tumor necrosis factor-Î± in the intervention groups was
4.06 lower
(5.34–2.77 lower)	629
(6 studies)	⊕⊕⊕⊝
moderate§,∥,¶	
Hospitalization duration	The mean hospitalization duration in the intervention groups was
1.44 lower
(1.91–0.97 lower)	981
(6 studies)	⊕⊕⊕⊝
moderate§	
The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95%CI).

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

CI = confidence interval; RR = risk ratio.

* Some of the studies included a small number of patients.

† There is significant publication bias.

‡ Some studies show a dose–response relationship.

§ Some studies were not randomized.

∥ The effect size is relatively significant.

¶ The effect size MD was large.

In the GRADE evidence grading, most outcome indicators were of moderate quality, enhancing the credibility of outcomes such as overall efficacy, symptom relief time, lung function, and serological indicators. However, 3 outcome indicators were of low quality, which may impact the reliability of the conclusions. The specific reasons for the downgrading of the studies were indicated in the table’s footnotes. Most downgrades were due to the risk of bias in outcome indicators, which may be related to the improper implementation of randomization and blinding methods. A few studies showed significant differences in effect sizes between groups, leading to a downgrade for inconsistency, or a downgrade for publication bias, which may be associated with the small number of patients included in the studies, considering the possibility of unpublished negative results. Therefore, researchers should standardize experimental design and ensure rigorous implementation in future studies.

3.4. Trial sequential analysis results

Through TSA for all outcome indicators, the results showed that the cumulative Z-value curves for treatment efficacy, disappearance time of wheezing, fever, pulmonary rales, C-reactive protein, tumor necrosis factor-α, and time of hospitalization all exceeded both conventional and TSA boundaries, reaching the RIS, and leading to positive conclusions. However, the TSA results for the lung function indicator FEV1/FVC and the “other types” subgroup of cough disappearance were unstable, with cumulative Z-values exceeding the conventional threshold but then decreasing, indicating the need for additional studies to confirm these findings. The specific results were shown in Figure 3.

Figure 3. TSA results of the included studies. TSA = trial sequential analysis.

3.5. Meta-analysis results

3.5.1. Treatment effects

All 31 studies[20–38, 44, 50] encompassing a total of 4073 patients, consistently reported variations in treatment effects when comparing the use of BG alone or in combination with WT against the use of WT alone. A low level of heterogeneity was observed (P = .94, I2 = 0%), prompting the application of a fixed-effects model for the analysis. The results revealed that the overall clinical efficacy in treating patients with RTIs using BG, or a combination of BG and WT, surpassed that of treatment with WT alone. This difference was statistically significant (RR = 1.19, 95%CI: 1.16–1.22, P < .001), as illustrated in Figure 4.

Figure 4. Forest plot of the treatment effect in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.2. Symptom resolution time

3.5.2.1. Wheezing disappearance time

Among the 31 studies included, 4[22, 25, 40, 50] specifically addressed the time of wheezing disappearance in patients treated with BG in combination with WT compared to those treated with WT alone. A total of 461 patients participated in these RCTs. The analysis detected significant heterogeneity (P < .001, I2 = 96%), indicating substantial variability in the results. Consequently, a random-effects model was applied for the analysis. The findings demonstrated a significant reduction in the time of wheezing disappearance with the addition of BG to WT, showing a statistically significant difference (RR = −1.62, 95%CI: −2.59 to −0.65, P = .001). Upon excluding the study conducted by Li Wen, the heterogeneity notably decreased to I2 = 69%, with the RR = −1.10. When reviewing Li Wen original article, it was identified that the treatment duration in this study extended to 4 weeks, surpassing the treatment duration in the other studies. This divergence in treatment duration could be a potential source of heterogeneity, suggesting that a longer treatment duration might lead to a quicker resolution of wheezing symptoms. This was represented in Figure 5.

Figure 5. Forest plot of the wheezing disappearance time in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.2.2. Pulmonary rales disappearance time

Within the pool of 31 included studies, ten specifically addressed the duration of pulmonary rales disappearance when comparing the combination of BG with WT against WT alone. These RCTs comprised a total of 1306 patients and were categorized into 3 subgroups based on distinct diseases: mycoplasma pneumonia, acute upper respiratory tract infections and other diseases (including acute bronchitis, whooping cough, and chronic bronchitis). The detailed analysis for each subgroup was delineated below.

Mycoplasma pneumonia subgroup: This subgroup included 3 publications[28,32,43] involving a total of 332 patients, and a low heterogeneity was observed (P = .35, I2 = 6%).The findings indicated a statistically significant acceleration in the disappearance of pulmonary rales when WT was combined with BG compared to WT alone, particularly in patients with mycoplasma pneumonia. (RR = −3.17, 95%CI: −3.56 to −2.78, P < .001).

Acute upper respiratory tract infections subgroup: 4 publications[21,29,40,41] encompassing 472 patients were included in this subgroup. High heterogeneity (P < .001, I2 = 96%) was observed, necessitating the application of a random-effects model for the analysis. The observed difference was statistically significant (RR = −1.55, 95%CI: −2.42 to −0.68, P < .001).

Other diseases subgroup: Three publications[23, 46, 48] involving 502 patients were incorporated in this subgroup. Heterogeneity was found to be low (P = .52, I2 = 0%), and the difference was statistically significant (RR = −1.06, 95%CI: −1.19 to −0.93, P < .001).

Substantial heterogeneity was identified among the 3 subgroups (P < .001, I2 = 96%). The findings indicated a statistically significant acceleration in the time of pulmonary rales disappearance when WT was combined with BG compared to WT alone in patients with RTIs. The difference was statistically significant (RR = −1.81, 95%CI: −2.25 to −1.38, P < .001). Additional comprehensive information was available in Table 3 and Figure 6.

Table 3 Pulmonary rales disappearance time subgroup results of BG in the treatment of RTIs.

Subgroups	Studies	Patients	RR [95%CI]	P	
Mycoplasma pneumonia	3	332	‐3.17 [‐3.56, ‐2.78]	<.001	
Acute upper respiratory infection	4	472	‐1.55 [‐2.42, ‐0.68]	<.001	
Other diseases	3	502	‐1.06 [‐1.19, ‐0.93]	<.001	
Total	10	1306	‐1.81 [‐2.25, ‐1.38]	<.001	

Figure 6. Forest plot of subgroup analysis for pulmonary rales disappearance in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.2.3. Fever disappearance time

Within the 31 studies considered, 17 studies[21, 23, 25, 27–29, 31–33, 35, 37–39, 42, 43, 47, 49] reported on the time it took for fever to disappear when BG were used alone or in combination with WT compared to WT alone. A total of 2192 patients participated in these RCTs. The analysis revealed significant heterogeneity (P < .001, I2 = 98%) indicating substantial variability in the results. Consequently, a random-effects model was applied for the analysis. The results revealed that the use of BG, either alone or in combination with WT, significantly reduced the time for fever resolution, with a statistically significant difference (RR = −1.32, 95%CI: −1.65 to −1.00, P < .001), as shown in Figure 7.

Figure 7. Forest plot of the fever disappearance time in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.2.4. Cough disappearance time

Of the 31 included studies, 15 addressed the duration of cough disappearance when comparing the combination of BG with WT against WT alone. This subset comprised 1896 patients and was classified into 5 subgroups based on specific diseases: acute bronchitis, mycoplasma pneumonia, bronchiolitis, acute upper respiratory tract infections, and other types (including whooping cough, cough-variant asthma, chronic bronchitis, and severe pneumonia). Individual subgroup analyses were presented below:

Acute bronchitis subgroup: Three publications[21,36,41] with totally 324 patients. High heterogeneity was observed (P < .001, I2 = 98%). The findings indicated a statistically significant acceleration in the time of cough disappearance with the combination of WT and BG compared to WT alone (RR = −1.58, 95%CI: −2.25 to −0.92, P < .001).

Mycoplasma pneumonia subgroup: Comprised 4 publications[25,28,32,43] with 445 patients. High heterogeneity (P < .001, I2 = 94%) necessitated the use of a random-effects model. The difference was statistically significant (RR = −2.55, 95%CI: −3.79 to −1.31, P < .001).

Bronchiolitis subgroup: Included 2 publications[22, 50] with 244 patients. High heterogeneity was estimated (P < .001, I2 = 93%), and the difference was statistically significant (RR = −1.58, 95%CI: −2.51 to −0.65, P < .001).

Acute upper respiratory tract infections subgroup: Comprised 2 publications[29,40] with 284 patients. Low heterogeneity was found (P = .51, I2 = 0%), and the difference was statistically significant (RR = −1.26, 95%CI: −1.49 to −1.03, P < .001).

Other types subgroup: Included 4 publications[23, 26, 46, 48] with 599 patients. High heterogeneity was observed (P < .001, I2 = 99%), and the difference was statistically significant (RR = −1.49, 95%CI: −3.12 to 0.13, P < .001).

Considerable heterogeneity was identified among the subgroups (P < .001, I2 = 98%). After excluding the study conducted by Li Wen and Shi Hua from the mycoplasma pneumonia subgroup, the heterogeneity decreased to I2 = 14%; in the “other types” subgroup, excluding Li Wen study reduced the heterogeneity to I2 = 32%, suggesting that treatment duration and disease specificity might be sources of heterogeneity. The overall results showed that the combination of BG and WT in patients with RTIs resulted in a significantly faster disappearance of cough compared to the use of WT alone. The difference was statistically significant (RR = −1.77, 95%CI: −2.23 to −1.30, P < .001). Further details were available in Table 4 and Figure 8.

Table 4 Cough disappearance time subgroup results of BG in the treatment of RTIs.

Subgroups	Studies	Patients	RR [95%CI]	P	
Acute bronchitis	3	324	‐1.58 [‐2.25, ‐0.92]	<.001	
Mycoplasma pneumonia	4	445	‐2.55 [‐3.79, ‐1.31]	<.001	
Bronchiolitis	2	244	‐1.58 [‐2.51, ‐0.65]	<.001	
Acute upper respiratory tract infection	2	284	‐1.26 [‐1.49, ‐1.03]	<.001	
Other types	4	599	‐1.49 [‐3.12, 0.13]	=.07	
Total	15	1896	‐1.77 [‐2.23, ‐1.30]	<.001	

Figure 8. Forest plot of subgroup analysis for cough disappearance in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.3. Pulmonary function index changes

Within the 31 studies considered, 4[20, 25, 26, 46] investigated the changes in the FEV1/FVC index before and after the administration of BG in combination with WT compared to WT alone, involving a total of 475 patients. The analysis revealed significant heterogeneity (P < .001, I2 = 93%), prompting the use of a random-effects model. After excluding the study conducted by Li Wen, the heterogeneity decreased substantially to I2 = 33%. Closer examination of the original data revealed that the baseline FEV1/FVC values in both the trial and control groups in Li Wen study were considerably lower than those observed in the other studies. The results indicated that the addition of BG to WT led to a significant increase in the FEV1/FVC index (RR = 4.09, 95%CI: 0.45 to 7.72, P < .001), as illustrated in Figure 9.

Figure 9. Forest plot of the FEV1/FVC index changes in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.4. Serological index changes

3.5.4.1. C-reactive protein

Among the 31 included studies, 6[21, 23, 35, 41, 42, 47] investigated changes in CRP levels before and after the administration of BG in combination with WT compared to WT alone, involving a total of 592 patients. The analysis revealed significant heterogeneity (P = .01, I2 = 66%), prompting the use of a random-effects model. After excluding the study conducted by Yan Silu, the heterogeneity decreased to I2 = 24%, suggesting that this study may have been one of the sources of the observed heterogeneity. Further examination of the original data revealed that the baseline CRP serum levels in the trial and control groups in Yan Silu study were significantly lower than those in the other studies. The results showed that the addition of BG to WT led to a significantly greater decrease in CRP levels (RR = −2.28, 95%CI: −2.61 to −1.95, P < .001), as illustrated in Figure 10.

Figure 10. Forest plot of the changes of C-reactive protein in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.4.2. Tumor necrosis factor-α

Among the 31 included studies, 6[21, 26, 35, 43, 46, 47] reported on changes in TNF-α levels before and after the administration of BG in combination with WT, compared to WT alone, encompassing 629 patients. The initial heterogeneity analysis revealed significant variability (P < .001, I2 = 98%), leading to the application of a random-effects model. After excluding the studies conducted by Feng Yecheng and Yang Huafei, the heterogeneity dramatically decreased to I2 = 0%. Further analysis indicated that baseline serum TNF-α levels were higher in both the trial and control groups in these 2 studies compared to others. The results demonstrated that the combination of BG and WT led to a significantly faster decrease in serum TNF-α levels, with a statistically significant difference (RR = ‐4.32, 95%CI: −5.82 to −2.82, P < .001), as illustrated in Figure 11.

Figure 11. Forest plot of the TNF-α changes in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.5. Hospitalization duration

Among the 31 included studies, 6[23, 29, 35, 48–50] investigated the impact of hospitalization duration after administering BG in combination with WT compared to WT alone, involving a total of 981 patients. Initial analysis revealed high heterogeneity (P = .001, I2 = 80%), necessitating the use of a random-effects model. After excluding the study conducted by Zhou Yongkang, heterogeneity decreased to I2 = 46%. Upon reviewing the original article, it was noted that the disease studied by Zhou Yongkang involved severe pneumonia in children, which likely contributed to a longer hospitalization duration compared to the other studies. The results indicated that the combination of BG and WT significantly reduced hospitalization duration compared to WT alone, with a statistically significant difference (RR = −1.44, 95%CI: −1.91 to −0.97, P < .001). Figure 12 illustrated the forest plot of hospitalization duration.

Figure 12. Forest plot of the hospitalization duration in RTIs treated with BG. BG = Bairui granules, RTIs = respiratory tract infections.

3.5.6. Sensitivity analysis and publication bias

A sensitivity analysis was conducted to evaluate the robustness of the treatment effects, revealing no qualitative changes. This indicated the stability of the results, as illustrated in Figure 13.

Figure 13. Distribution of sensitivity to the treatment effect of BG in the treatment of RTIs. BG = Bairui granules, RTIs = respiratory tract infections.

To assess potential publication bias, a funnel plot for treatment effects was depicted in Figure 14. The plot showed an empty space in the lower left corner, indicating a “missing corner” situation. This suggested that studies with smaller sample sizes were more likely to report positive results, indicating the presence of publication bias. To further evaluate this bias, Egger test results showed P = .00 < .05, confirming the presence of publication bias. To correct this bias, we used the trim and fill method to estimate and fill in 12 potentially missing studies. The funnel plot adjusted by the trim and fill method showed more symmetry (Fig. 15). After adjustment, the combined effect size under the random effects model increased from 1.173 to 3.157 (95%CI: 3.080–3.236), with heterogeneity (Q = 55.250, P = .083), indicating that the results are robust and the treatment effect is significant. Using TSA we determined that the current volume of literature included was sufficient to support the results. Therefore, the use of BG therapy for respiratory diseases was recommended based on the available evidence.

Figure 14. Funnel plot of the treatment effect of BG in the treatment of RTIs. BG = Bairui granules, RTIs= respiratory tract infections.

Figure 15. Trim and fill result plot.

4. Discussion

RTIs are common diseases in pulmonology, affecting individuals of all age groups, especially children.[51] Bacteria, viruses, mycoplasma, fungi, and parasites often serve as the pathogens for these infections, with the majority caused by viral infections.[52] RTIs are divided into upper and lower respiratory tract infections, which, although primarily affecting different locations, are significantly linked. Upper respiratory tract infections account for 90% of common cold cases, while lower respiratory tract infections are prevalent in clinical medical practice and mainly include chronic bronchitis, acute tracheobronchitis, and bacterial pneumonia.[53] RTIs are associated with a high number of deaths and have a high clinical incidence rate. Conventional western medicine typically administers antibiotics and antiviral drugs for symptomatic treatment; however, these approaches have limitations such as treatment timing windows, the inability of antiviral treatments to shorten the course of illness, and slow improvement in clinical symptoms.

Bairui Granules, initially recorded in “Tujing Bencao,” were characterized by their spicy, slightly bitter taste, and cold nature, entering the lung, spleen, and kidney meridians.[54] They contained various bioactive components such as flavonoids, organic acids, alkaloids, tannins, phenols, polysaccharides, sterols, volatile oils, minerals, and mannitol,[9] which exhibited antimicrobial, antioxidant, anti-inflammatory, antiviral, and immune-enhancing activities.[55] Clinically, they were often used to treat upper respiratory tract infections and seasonal flu.[22] Studies exploring the mechanisms of Bairui granules in treating viral pneumonia found that they were associated with reducing lung tissue viral load and serum inflammatory cytokines IL-6, TNF-α, and IFN-γ levels.[56] Modern pharmacological research indicated that flavonoids and alkaloids in Bairui granules possessed anti-inflammatory, antibacterial, antiviral, and antioxidant properties.[57] Research reports suggested that the anti-inflammatory effects of kaempferol derivatives from Bairui granules were related to the inhibition of intracellular reactive oxygen species production and the activation of p38 MAPK and AP-1. Furthermore, Bairui Compound I could inhibit the expression of inflammatory cytokines TNF-α, IL-6, and IL-1β through the NF-κB and MAPK pathways.[58] Other studies identified the absorbed components and metabolites of Bairui Granules, detecting alkaloids such as matrine and sophocarpine and flavonoids primarily as kaempferol aglycones, clarifying the pharmacological basis of their efficacy,[59] which closely aligned with the outcome indicators selected in this study. The funnel plot in this study displayed asymmetry, indicating potential publication bias. However, trial sequential analysis suggested that the number of included studies reached the RIS, and the cumulative Z-value curve surpassed the traditional threshold. Therefore, the use of BG for RTIs is recommended.

This study extended the search period until the end of November 2023, including a total of 31 RCTs. By incorporating the latest clinical research findings, the study expanded its scope of evaluation. It examined not only clinical efficacy and hospital stay duration but also several outcome measures such as pulmonary function (FEV1/FVC) and serum biomarkers. For outcomes with high heterogeneity, a systematic exclusion strategy was employed to identify sources of heterogeneity and assess result stability. However, this study has limitations: (1) some RCTs lacked explicit mention of concealed random sequence allocation or blinding procedures, introducing potential selection bias, and diminishing methodological quality; (2) the inclusion of only Chinese literature restricted the breadth of data support; (3) the complex nature of the diseases considered might have contributed to considerable heterogeneity. Despite these limitations, the study underscored the potential benefits of BG in treating RTIs and supported its further promotion and investigation. Future research should involve larger-scale, multi-center, randomized clinical trials to provide more robust clinical evidence.

Overall, this study conducted a comprehensive analysis and assessment of the efficacy and safety of BG therapy for RTIs, providing a novel evidence-based medicine foundation for judicious treatment. The highlighted limitations necessitate further research to thoroughly validate the clinical efficacy and safety of BG. Subsequent studies, particularly those that are larger, multi-centered, and designed as prospective randomized double-blind trials, are imperative to strengthen and substantiate these findings. This elucidates the advantages of using Bairui granules alone or in combination with Western medicine in clinical applications, providing a rational basis for clinical practice.

5. Conclusion

In conclusion, our study investigated the effectiveness and safety of BG, either alone or in combination with conventional WT, compared to WT alone for treating RTIs. The findings demonstrated that BG significantly enhanced clinical efficacy, accelerated symptom resolution, and reduced hospitalization duration for patients. Moreover, the study emphasizes the potential benefits of incorporating additional outcomes in clinical trials involving TCM treatments, which could enrich the clinical evaluation system.

Author contributions

Conceptualization: Jiaqi Li, Jiarui Wu.

Data curation: Yueqin Guan.

Formal analysis: Keyan Chai, Yueqin Guan.

Investigation: Siyun Yang.

Methodology: Haojia Wang, Rui Shi, Yiyan Zhai.

Resources: Haojia Wang, Rui Shi, Chuanqi Qiao.

Software: Jiying Zhou.

Supervision: Xiaomeng Zhang, Jiarui Wu.

Validation: Jiarui Wu.

Writing – original draft: Keyan Chai, Haojia Wang.

Writing – review & editing: Keyan Chai, Antony Stalin.

Supplementary Material

Abbreviations:

95%CI = 95% credible interval

BG Bairui granules

CRP C-reactive protein

RCTs randomized controlled trials

RIS required information size

RR relative risk

RTIs respiratory tract infections

TCM Traditional Chinese Medicine

TNF-α tumor necrosis factor-α

TSA trial sequential analysis

URTIs upper respiratory tract infections

WT Western medicine treatment

The study was financially supported by the National Natural Science Foundation of China (Grant nos. 82074284), State administration of Traditional Chinese Medicine High-level Key Discipline Construction Project – Clinical Chinese Pharmacy (No. ZYYZDXK-2023257), Beijing University of Chinese Medicine Corporate Collaboration Project (No. BUCM-2023-JS-FW-067).

This study is a systematic review of multiple clinical randomized controlled trials, and all included literature is published and does not involve ethical approval.

The authors have no conflicts of interest to disclose.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Supplemental Digital Content is available for this article.

How to cite this article: Chai K, Wang H, Guan Y, Shi R, Stalin A, Zhai Y, Zhou J, Qiao C, Yang S, Li J, Zhang X, Wu J. Effectiveness of Bairui granules in the treatment of respiratory tract infections: A systematic review and meta-analysis. Medicine 2024;103:29(e38904).
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References

[1] Gu W Deng X Lee M . Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids. Nat Med. 2021;27 :115–24.33169017
[2] Zuo XP Li Z Li FS . Research progress on the mechanism of Qingre Jiedu method in treating infectious respiratory diseases. J Liaoning Univ Tradit Chin Med. 2023;25 :203–7.
[3] Project CCoEoLMT. Adult respiratory tract infection pathogen diagnosis nucleic acid testing technology clinical application expert consensus (2023). Med J Peking Union Med Coll Hosp. 2023;14 :959–71.
[4] Ma HX Lao ZY . Clinical study of children resuqing granule combined with cefixime in the treatment of upper respiratory tract infection in children. Res Integr Tradit Chin West Med. 2023;15 :230–3.
[5] Rong P Ma R Liu QH . A commentary of literature research of traditional Chinese medicine for acute upper respiratory tract infection in children. Zhongguo Zhong Yao Za Zhi. 2017;42 :1455–66.29071847
[6] Wang TL Wang MM . Progress in traditional Chinese medicine for the treatment of acute upper respiratory tract infections in children. J Emerg Tradit Chin Med. 2011;20 :944–5.
[7] Gu MD Liang YF Deng LS . Clinical observation of the therapeutic effect of Bairui granules on 150 cases of upper respiratory tract infection. Paper presented at: The 14th National Academic Symposium on Traditional Chinese Medicine Internal Medicine Pulmonary Diseases 2010; Hailar, Inner Mongolia, China.
[8] Zhu MW Ma WX . Clinical observation of Bairui granules combined with ribavirin aerosol in the treatment of children with seasonal influenza. China Pharm. 2015;18 :1343–5.
[9] Liao YY Zhou GQ . Research progress on the clinical application of Bairui granules. J Mod Med Health. 2021;37 :1149–52.
[10] Yao J Zhao J Wen JR . Flavonoid-containing supplements for preventing acute respiratory tract infections: a systematic review and meta-analysis of 20 randomized controlled trials. Complement Ther Med. 2022;70 :102865.35940344
[11] Zhou SQ Fang Y Tan JT . Study on the blood components of Bairei granules based on UHPLC-Q-TOF-MS/MS technology. Nat Prod Res Dev. 2023;36 :1–9.
[12] Higgins JP Altman DG Gøtzsche PC . The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343 :d5928.22008217
[13] Sterne JAC Savović J Page MJ . RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366 :l4898.31462531
[14] Mendoza C Kraemer P Herrera P . Clinical guidelines using the GRADE system (Grading of recommendations assessment, development and evaluation). Rev Med Chil. 2017;145 :1463–70.29664529
[15] Shao M Chen YT Xu W . Principles of sequential analysis in experiments and its application in meta-analysis. Chin J Health Stat. 2022;39 :47–51.
[16] Wang Q Tian JH Li L . Introduction to sequential analysis in experiments. Chin J Evid Based Med. 2013;13 :1265–8.
[17] Weng H Guo CC Lv J . Calculation of information in sequential analysis of experiments. Chin J Evid Based Med. 2017;17 :113–6.
[18] Xia Y Sun Y Liu ZL Liu JP . Sample size estimation for systematic review or meta-analysis using sequential analysis in experiments. Mod Chin Clin Med. 2013;20 :31–3.
[19] Higgins JP Green S . Cochrane handbook for systematic reviews of interventions. 2008.
[20] Deng LP Yang Y Wang JM . Effect of Bairui granules on lung function and serum levels of COX-2 and sTREM-1 in patients with chronic obstructive pulmonary disease. World J Integr Tradit West Med. 2022;17 :2215–2218 + 2222.
[21] Feng Y Fu CS Fu ZM Wang D . Clinical study of Bairui granules combined with Cefaclor granules in treatment of acute bronchitis in children. Drug Eval Res. 2020;43 :95–7.
[22] Guo AL Zhu WW Zhu J Qiu LJ . Clinical observation on the treatment for bronchiolitis in children with Bairui granules and atomization. Chin Pediatr Integr Tradit West Med. 2017;9 :46–8.
[23] He J . Effect of Bairui granules combined with erythromycin on the treatment of pertussis in children and its influence on the levels of inflammatory factors. J China Prescr Drug. 2020;18 :108–10.
[24] Huang YX . The clinical efficacy and safety of cefoperazone/sulbactam combined with Bairui granules as adjunctive therapy for chronic obstructive pulmonary disease. Chin J Clin Ration Drug Use. 2021;14 :78–80.
[25] Li W Shi H Zhao WW . Efficacy of Bairui Granules combined with azithromycin and budesonide inhalation in the treatment of mycoplasma pneumoniae infection complicated with childhood vasomotor asthma and its impact on pulmonary function. Prog Mod Biomed. 2020;20 :1553–6.
[26] Li W Zhao WW Ge JM . Effects of Bairui granules combined with azithromycin and budesonide inhalation on pulmonary function and inflammatory factors in children with cough-variant asthma. Prog Mod Biomed. 2020;20 :3156–9.
[27] Li XJ Li YM Yan J . Efficacy and safety of Bairui particles combined with ribavirin in the treatment of children with herpangina. Guide Chin Med. 2018;16 :25 + 27.
[28] Li YY Chen QW . Efficacy analysis of Bairui particles as adjuvant therapy for children with mycoplasma pneumonia. Chin Pediatr Integr Tradit West Med. 2016;8 :575–7.
[29] Ma WX . Clinical observation of adjuvant therapy with Bairui particles for children with acute upper respiratory tract infection. China Pharm. 2015;18 :606–8.
[30] Ma YW . Clinical efficacy observation of Bairui granules combined with ofloxacin ear drops in the treatment of acute suppurative otitis media in children. Health Req. 2021;34 :100.
[31] Mai ZY . Exploration of the clinical effects of Bairui granules in the treatment of herpetic pharyngitis. Mod Med Health Res Electron J. 2018;2 :161–2.
[32] Mai ZY Yang XQ . Therapeutic effect of Bairui granules as an adjuvant treatment for mycoplasma pneumonia in children. Electron J Clin Med Lit. 2019;6 :155–6.
[33] Rao LF Zhu XP Sun H . Observation on the therapeutic efficacy of Bairui granules in the treatment of herpetic pharyngitis. Strait Pharm J. 2018;30 :95–7.
[34] Ren XC . Clinical observation on the therapeutic effect of Bairui granules combined with ofloxacin ear drops in the treatment of acute suppurative otitis media in children. Health Req. 2021;21 :75.
[35] Song Q Zhao LH Li XQ . Clinical efficacy of Bairui granules in the treatment of herpetic pharyngitis. Chin J Clin Ration Drug Use. 2023;16 :94–7.
[36] Sun L . Curative effect of Bairui granule in the treatment of acute bronchitis in children. Guide China Med. 2021;19 :128–9.
[37] Tian Y . Analysis of therapeutic effect of Bairui particles for herpangina. Chin Med Mod Dis Educ China. 2014;12 :35–6.
[38] Wang JX Wang YT Liu HQ Li GY . Clinical effect observation of Bairui granules combined with amoxicillin and clavulanate potassium tablets in treating acute tonsillitis. Chin Tradit Herb Drugs. 2018;49 :5889–91.
[39] Wang WH Yan SQ Deng YP Tang JQ . Observation on the therapeutic efficacy of Bairui granules in the treatment of herpetic pharyngitis in children. Med Inf. 2013;26 :215.
[40] Wei YM Qiao YX Qi WB . Clinical efficacy of Bairui particles combined with ribavirin in the treatment of children with acute upper respiratory infection. Chin J Front Med Sci. 2015;7 :165–7.
[41] Xu B Guo JJ Liu HQ Fei HT Chen M . Clinical study of Bairei granules combined with cefixime sodium in the treatment of acute bronchitis in children. Prog Mod Biomed. 2023;23 :3397–400.
[42] Yan SL Chen XF . Clinical evaluation of Bairui granules combined with amoxicillin sodium and clavulanate potassium for injection in the treatment of children with suppurative tonsillitis. Basic Tradit Chin Med. 2023;2 :48–52.
[43] Yang HF Xia HB Fan HS You P . Clinical study on Bairui granules combined with azithromycin for children with mycoplasma pneumonia. New Chin Med. 2023;55 :124–8.
[44] Ye JB . Analysis of the therapeutic effect of combined use of Bairui Granules and Ofloxacin ear drops for children with a cute suppurative otitis media. Contemporary Med Symp. 2019;17 :143–4.
[45] Zhao P . Therapeutic effect of Ofloxacin ear drops combined with Bairui Granules on acute suppurative otitis media in children. Chin Tradit Herb Drugs. 2019;50 :681–4.
[46] Zheng YW Xu LF Li ZY . Clinical study of Bairui granules combined with ambroxol nebulization in the treatment of acute exacerbation of chronic bronchitis. Int J Tradit Chin Med. 2020;42 :221–5.
[47] Zhong JX Huo KM Gu YN Wu XH Chen HB . Efficacy of Bairei granules combined with cefprozil in the treatment of acute tonsillitis and its impact on serum inflammatory factor levels. Chin Arch Tradit Chin Med. 2022;40 :237–40.
[48] Zhou YK Yang JQ Zhao RP Dong R Tao ZB . Clinical observation of 150 cases of severe pneumonia in children treated with Bairei granules as adjuvant therapy. J Pediatr Tradit Chin Med. 2023;19 :41–4.
[49] Zeng YY . Clinical observation on Bairui granules joined with interferon atomization inhalation in treating Herpangina in children. West J Tradit Chin Med. 2021;34 :113–5.
[50] Wang L Liu J . Observation on the therapeutic efficacy of nebulized inhalation of α-1b interferon combined with oral Bairui granules in the treatment of bronchiolitis. Acta Chin Med Pharmacol. 2017;45 :62–4.
[51] Liu YS Wang J Ma HL . The impact of thoracoscopic esophagectomy on postoperative pulmonary function and inflammatory factor release in patients with esophageal cancer. Guizhou Med J. 2019;43 :82–4.
[52] Zhu Q Pan J Xu J . Research progress on the treatment of respiratory tract infectious diseases with shufeng jiedu capsules. Chin Tradit Herb Drugs. 2022;53 :3557–63.
[53] Fu XX Wu J Jing J . Clinical efficacy of levofloxacin in the treatment of lower respiratory tract infectious diseases. Chin J Clin Rational Drug Use. 2021;14 :70–1.
[54] Song LS Zhang XM Guo QS Chen L Wang CL . Study on winter dormancy of Thesium chinense and its phenological phase. Zhongguo Zhong Yao Za Zhi. 2015;40 :4585–90.27141667
[55] Yi Z Min H Xiao-Fang Y . Isolation of chemical components from Thesium chinense. Chin J Exp Tradit Med Formulae. 2016;7 .
[56] Deng YR Sun JH Hao LX . Effect and mechanism of Bailui granules on influenza virus pneumonia in mice. Chin J Pharmacovigil. 2023;20 :1249–55.
[57] Maleki SJ Crespo JF Cabanillas B . Anti-inflammatory effects of flavonoids. Food Chem. 2019;299 :125124.31288163
[58] Yan Y Li X Zhang C Lv L Gao B Li M . Research progress on antibacterial activities and mechanisms of natural alkaloids: a review. Antibiotics (Basel). 2021;10 :318.33808601
[59] Zhou SQ Fang Y Tan JT . Study on blood components of Bailui granules based on UHPLC-Q-TOF-MS/MS technique. Nat Prod Res Dev. 2024;36 :243–51.
