Study design and Registration
We will follow the scoping review methodology developed by Arksey and O’Malley [21] and other authors [22,23]. This scoping review protocol complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extensions for Scoping reviews, (PRISMA-Scr) guidelines [23]. This review protocol has been registered with the Open Science Framework on February 12, 2021 (https://osf.io/s7uvk/).
Stage 1: Identifying the Study questions
This stage was archived with a preliminary literature search on previous research and agreement of research team members for better scoping of research objectives. The research team comprised one respiratory disease specialist (KK), a specialist in clinical research on traditional East Asian medicine (JL), and a researcher on literature review (YK). Suggestions and revision of the research question were requested from other related experimental research experts. The following questions will be addressed in our scoping review following the consensus of the research team.
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What is the popular herbal medicine prescribed for lung disease induced by PM and which herbal medicine is better for each indication?
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What is the primary and secondary outcome reported in the studies on lung disease induced by PM?
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What types of mechanisms were explored regarding the effect of herbal medicine for lung disease induced by PM?
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What are the known adverse events of herbal medicine for lung disease induced by PM?
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How long should the herbal medicine be prescribed?
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What types of animal models are frequently used in experimental research and what are the strengths and limitations of each model?
Stage 2: Identifying relevant studies
2.1 Information source
We will restrict our research to peer-reviewed; English-language studies examining the efficacy of herbs in respiratory disease induced by PM will be included. The literature search will be conducted from the inception to the present (March 2021). The following databases will be searched: MEDLINE (via PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials. The reference lists of the retrieved articles and the relevant systematic reviews will be searched manually. Efforts will be made to get in touch with the authors of the published articles of which electronic files could not be obtained. The search strategy was consulted with the librarian, an expert on scoping review, and a specialist on lung disease. We will use search terms related to PM and intervention. Related medical subject heading (MeSH) terms and synonyms in various combinations will be used in the search strategy. The terms to be used in relation to PM include “fine dust,” “PM,” and “coarse particle.” The terms to be used in relation to intervention include “herbal medicine” and “herb.” The search strategies are presented in supplementary digital content (Appendix 1).
2.2 Eligibility criteria: Types of Studies
Only controlled comparative in-vivo/in-vitro studies examining the effects of herbs in animal models of respiratory disease induced by PM will be included.
2.3 Eligibility criteria: Types of Animal model
All types of animal models will be included; there will be no restrictions on species, sex, and age.
2.4 Eligibility criteria: Types of Interventions
Multiple or single medicinal herb preparations and fractions of medicinal herb preparations will be considered eligible as interventions. We will include herbal preparations of any type, such as liquids, gels, tablets, and extracts, but only those that are orally administered. Any type of comparative intervention will be included. The duration of the treatment period will not be restricted.
2.5 Eligibility criteria: Types of Outcome Measurements
The last time-point acquired value will be extracted. The primary outcome will be respiratory function. The secondary outcomes will be as follows: 1) inflammatory markers, 2) reactive oxygen species (ROS), and 3) histology and mechanisms. In terms of safety issues, we will also investigate adverse events and dropout rates.
Stage 3: Study selection
Two reviewers (YK and JL) will independently conduct the entire study selection process. After performing database searches and eliminating duplicate publications, the titles and abstracts of the searched studies will be screened for inclusion. For the articles identified as potentially relevant, the full text will be checked to determine whether the study will be included. All articles will be included or excluded based on predetermined criteria, and the reviewers will record the reasons for exclusion. Any discrepancies will be resolved through discussion with another researcher. The details of the study selection procedure are presented in Figure 1.
Stage 4: Charting the data
A preliminary data extraction sheet was developed with agreement on the pilot testing by the research team. After several revisions, a standardized data extraction form was developed.
4.1 Data extraction
The following items will be extracted from the included studies: general information, such as the last name of the first author and publication year; characteristics of the animals, such as species, sex, age, and weight; the respiratory models employed; methods for inducing respiratory disease; type of respiratory disease induced; details regarding the PM, such as type, origin, characteristics, and method by which it was obtained; herbal medicines characteristics, such as route of administration, composition, dosage, and treatment period; and details of the control intervention. Data regarding research results (effect and safety), research findings, and proposed mechanisms will be extracted.
The data extraction process will be performed independently by two reviewers (YK, JL); these reviewers will crosscheck data from all of the included studies. Any disagreement between the two reviewers will be resolved through discussion with another researcher (KIK).
4.2 Assessment of the methodological quality and risk of bias of included studies
The inclusion of quality assessment in scoping reviews is controversial [24]. After discussion and consultation, we decided to include quality assessment for a better understanding of the methodological and reporting quality of the research community. The methodological quality of all included studies will be evaluated using the systematic review center for laboratory animal experimentation (SYRCLE’s) risk of bias tool for animal studies [25]. This tool consists of 10 items and reflects the six aspects of the risk of bias: (1) selection bias (sequence generation, baseline characteristics, and allocation concealment), (2) performance bias (random housing and blinding), (3) detection bias (random outcome assessment and blinding), (4) attrition bias (incomplete outcome data), (5) reporting bias (selective outcome reporting), and (6) other sources of bias. For the consistency of critical appraisal, a pilot quality assessment will be conducted. Each reviewer will conduct a separate quality assessment. For each item, “yes” indicates a low risk of bias, “no” indicates a high risk of bias, and “unclear” indicates insufficient details to determine the risk of bias.
Stage 5: Collating, Summarizing and reporting the results
Extracted data will be utilized to develop an analytical framework for collating, synthesizing, and summarizing the extracted data. In the qualitative analysis stage, we will provide a table named ‘Characteristics of included studies,’ including the author, published year, country, animal model, number of analyzed participants, treatment group intervention (herbal medicine and composition) and dosage, control group intervention and dosage, and reported outcomes. We will also provide another table named ‘Effect, mechanism, and safety herbal medicine for lung disease induced by PM. The results of the experiment are presented according to each intervention and dosage, possible mechanism suggested by the original research author, and the number of each adverse event. We will also gather research implications for further research from original articles that can be helpful for the research community. We will also provide a figure named ‘Research map,’ which will visualize possible mechanisms and candidate herbal preparation/medicinal plants. All of the processes for qualitative analysis will be conducted using Microsoft Excel.
If possible, we will conduct a quantitative synthesis of the extracted data. We will import the quantitative data into Review Manager software (version 5.3). For continuous variables, outcome measures will be represented as mean differences (MDs) with 95% confidence intervals (CIs). For binary variables, outcome measures will be represented by frequency and ratio. We will use random effects models for pooled-effect estimates; these models consider the variation between studies and assign weights for each study accordingly. Between-study heterogeneity will be measured using the Chi-square test (using a significance threshold of p < 0.1) and quantified using the I² statistic. I² values < 25%, < 50%, and ≥ 50% indicate low, moderate, and high heterogeneity, respectively. If applicable, we will conduct subgroup analysis based on the herbal medicine classification and treatment duration.