Mycoplasma pneumoniae is a common respiratory pathogen that is responsible for the community-acquired pneumonia (CAP), especially in children.[1–3] Furthermore, it also triggers the exacerbation of asthmatic symptoms and wheezes in children.[4–9] It has been reported that M pneumoniae accounts for 7% to 40% of all CAP in children 3 to 15 years of age. Fortunately, it has a lower incidence in children under 3 years old. Other respiratory conditions are also reported to have association with M pneumoniae. These conditions often include tracheobronchitis, bronchopneumonia, pharyngitis, sinusitis, croup, and bronchiolitis.
Although the clinical significance of M pneumoniae infection is becoming evident, its pathophysiological mechanisms of serum inflammation factors (IF) in children still have not been fully understood. Several cytokines are reported to have associated with M pneumoniae.[12–18] These cytokines consist of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, and IL-17.[12–18] However, up to the present, no systematic review has been addressed to explore the associations between IF and M pneumoniae in pediatric population. Therefore, this study will firstly explore the associations between IF and M pneumoniae in pediatric patients.
2.1 Study registration
This study has been registered on PROSPERO (CRD42019125359) and has reported according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) statement.
2.2 Eligibility criteria for study selection
2.2.1 Types of studies
All randomized controlled trials (RCTs), observational studies or case-control studies will all be considered for inclusion in this study. However, non-clinical studies, case reports, case series will not be considered.
2.2.2 Types of participants
All pediatric patients with age <18 years old, and are clinically diagnosed with M pneumoniae, and have checked by IF, such as IL-4, IL-5, IL-6, IL-10, IL-13, and IL-17. Participants will be excluded if they are accompanied with other chronic respiratory diseases or disorders, such as cystic fibrosis, bronchiectasis, bronchopulmonary dysplasia, or immunodeficiency.
2.2.3 Types of exposures
Exposure includes IF following M pneumoniae will be considered as experimental exposures. Comparators are a group of participants without M pneumoniae.
2.2.4 Types of outcomes
The outcome measurements include any IF, such as IL-4, IL-5, IL-6, IL-10, IL-13, and IL-17.
2.3 Literature sources and search methods
2.3.1 Search strategy
We will comprehensively search the literature sources of PUBMED, PsycINFO, Scopus, Cochrane Library, EMBASE, Web of Science, and Chinese Biomedical Literature Database from inception to February 28, 2019 without any language restrictions. Additionally, reference lists of relevant studies will also be searched to avoid missing any potential studies. The detailed search strategy for Cochrane Library is presented in Table 1. Similar detailed search strategies will also apply to any other electronic databases.
2.3.2 Study selection
Two investigators will independently select the studies on the basis of the predefined eligibility criteria. The study selection will consist of 2 stages. First, all titles and abstracts will be scanned by 2 investigators. Second, both investigators will obtain full-text literature to further check those meet the inclusion criteria. The whole process of study selection is abided to the guidelines of PRISMA-P, and reasons for exclusions and inclusions of all articles will be shown in PRISMA flowchart. Any discrepancies will be resolved by consulting a third investigator through discussion.
2.3.3 Data extraction
All required data will be double extracted by 2 independent investigators using a pre-designed standardized data extraction form. Any disagreements regarding the data extraction will be solved by a third investigator through discussion. Data in detail will be extracted from each study as follows: title, first author name, year of publication, journal, country, study design, patient selection, age, sample size, types of exposures, outcome variables, and any other important information.
2.3.4 Dealing with essential missing information
Missing information or data will be inquired by contacting primary authors. If we can not get those data, we will just analyze the available data and will discuss its impacts as a limitation.
2.4 Methodological quality assessment
Methodological quality of each study will be evaluated by using Newcastle–Ottawa Scale checklist. This tool ranges from 0 (lowest quality) to 9 (best quality). Two independent investigators will assess the methodological quality for each study. Any disagreements regarding the methodological quality between 2 investigators will be resolved by consulting a third investigator. Summary risk of bias table will be built.
2.5 Statistical analysis
STATA 12.0 software will be used for statistical analysis in this study. If there are sufficient eligible studies, the data will be pooled, and meta-analysis will be conducted. Mean difference with 95% confidence intervals (CIs) will be used to summarize the continuous data. Risk ratio and 95% CIs will be utilized to express the dichotomous data. Heterogeneity across the included studies will be assessed by using I2 test. The acceptable heterogeneity will be considered if I2 ≤50%, then data will be pooled by using a fixed-effect model, and meta-analysis will be carried out. The substantial heterogeneity will be regarded if I2 >50%, and data will be pooled by using a random-effect model. Meanwhile, subgroup analysis will be performed. If substantial heterogeneity is still identified after subgroup analysis, data will not be pooled, and meta-analysis will not be conducted. However, we will still report the results as native summary.
2.6 Additional analysis
2.6.1 Subgroup analysis
Subgroup analysis will be performed based on different characteristics, outcome values, and study quality.
2.6.2 Sensitivity analysis
Sensitivity analysis will be operated to check the robustness and stability of pooled outcome results data by removing low-quality studies.
2.6.3 Reporting bias
Funnel plots and Egger regression test will be utilized to check the reporting bias if sufficient studies are included.
Several previous clinical studies have reported that IF has associations with M pneumoniae in children.[12–18] However, no systematic review and meta-analysis have explored the associations between IF and M pneumoniae in pediatric patients. Thus, in this study, we will systematically investigated the associations between IF and M pneumoniae in children by searching comprehensive literature databases. The results of the present study will summarize the latest evidence on the associations between IF and M pneumoniae in pediatric patients. The findings may also provide helpful evidence for both patients and clinicians.
Conceptualization: Jin-e He, Chun-Yan Gao.
Data curation: Jin-e He, Hui Qu, Chun-Yan Gao.
Formal analysis: Jin-e He, Hui Qu.
Funding acquisition: Jin-e He.
Investigation: Chun-Yan Gao.
Methodology: Jin-e He.
Project administration: Chun-Yan Gao.
Resources: Jin-e He, Hui Qu.
Software: Jin-e He, Hui Qu.
Supervision: Chun-Yan Gao.
Validation: Hui Qu, Chun-Yan Gao.
Visualization: Jin-e He, Hui Qu, Chun-Yan Gao.
Writing – Original Draft: Jin-e He, Hui Qu, Chun-Yan Gao.
Writing – Review & Editing: Jin-e He, Hui Qu, Chun-Yan Gao.
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