2.1. The registration
This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in January, 2021 (registration number CRD42021221638). We will describe the changes in the full review if necessary. The consent of this protocol report is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2020 statement guidelines. Furthermore, we elaborated the guiding question of this review, to ensure the systematic search of scientific literature using the PICOS (Population / Intervention / Comparison / Outcomes / Study Design).
2.2. Inclusion criteria for study selection
Table 1 shows the inclusion and exclusion criteria used in study screening, first by title and abstract and then by full text. Articles will be included if they are primary studies or systematic reviews of any study design. The study population must be composed of children or adolescents with asthma. Studies should investigate the role of vitamin D in asthma control and severity.
Table 1 – Inclusion and exclusion criteria
|Types of studies: randomized trials, observational studies (including cohort and case-control studies) and also secondary studies
||Types of studies: case report and letter to editor
|Population: patients between 2 and 18 years old, of all ethnicities and genders
||Population: adults, pregnant women, elderly, animals or infants with congenital heart defects
|Language: articles published in English
||Language: non-English articles
|Outcome: higher levels of vitamin D correspond with better control and less severity of asthma
||Outcome: recurrent wheezing by other causes
2.2.1. Study designs
This review will include all types of primary study design including randomised control trials, prospective observational case-control studies and cohort studies, published in English.
2.2.2. Type of participants
All children or adolescents diagnosed with asthma, and with serum vitamin D levels, without race or gender restrictions.
Interventions to be examined will include any studies of serum vitamin D in children and adolescents with asthma who have difficulty controlling the disease, use of high-dose corticosteroids, or had severe exacerbations during the intervention or follow-up.
The primary outcome:
Low vitamin D concentrations are related to higher risks of asthma exacerbations and most frequently the use of anti-inflammatory medications as corticosteroids.
The secondary outcome:
Vitamin D and its anti-inflammatory effect through the regulation of Treg cells. Vitamin D supplementation and its ability to improve asthma control, especially in patients with severe disease.
2.3. Data sources and search strategy
We will search the following electronic bibliographic databases: PubMed, BVS-BIREME, EMBASE, EBSCOhost, Scopus, Web of Science, ProQuest, and the Cochrane Library and will use the following search strategy: (Child OR Adolescent) AND Asthma AND ("Vitamin D" OR Cholecalciferol) AND ("Inflammation Mediators" OR Lymphocytes OR Biomarkers OR Interleukins).
2.4. Data collection and analysis
2.4.1. Selection of studies
The selected literature will be managed by using Rayyan, and the screening will be a two-step process, first by title and abstract, and then by full text. A third investigator will be involved in the case of any disagreements or inconsistency left unresolved by consensus. Duplicated articles will be identified and excluded. To get qualified studies, we will then screen the full text reports and decide whether these meet the inclusion criteria and then exclude studies with incomplete information. Details of the study selection procedure are shown in Figure 1.
2.4.2. Data extraction and management
Data from eligible articles will be extracted independently by 2 reviewers and any disagreements will be resolved by discussion with any ongoing differences in opinion being arbitrated by a third reviewer. Data extracted will be the following: study characteristics, author names, year published, patient characteristics, data needed for quality assessment and outcomes.
2.4.3. Assessment of risk of bias in included studies
The risk of bias for non-randomized studies will be assessed using Joanna Briggs critical appraisal Tools (JBI) for cross section studies and the Newcastle–Ottawa scale (NOS) for case-control studies and cohort, which assesses 3 parameters of study quality: selection, comparability, and exposure assessment. It assigns a maximum score of 4 for selection, 2 for comparability, and 3 for exposure, for a maximum total score of 9. Studies with a total NOS score of 5 or greater are considered to be of moderate to high quality, whereas those with an NOS score of less than 5 are considered low-quality studies. If we include randomized trial studies, we will assess their risks of bias with RoB 2.0 (a revised tool to assess the risks of bias in randomized trials). The quality of evidence for clinical outcomes will be assessed according to recommendations of the GRADE working group.