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Vitamin D plays an important role in enhancing mucosal immune defense, decreasing excessive inflammation, and increasing mucociliary clearance. Experimental studies have shown that vitamin D reduces inflammation of epithelial cells in airways infected with Respiratory Syncytial Virus and confers antiviral effects. Furthermore, several studies have shown lower serum vitamin D levels in hospitalized children with bronchiolitis. However, studies on the efficacy of Vitamin D supplementation for children with bronchiolitis are scarce with inconsistent findings. In this study, we aim to evaluate the efficacy of vitamin D supplementation in children with bronchiolitis.
Bronchiolitis is the most frequent lower respiratory tract infection in children under two years of age, which represents a major cause of medical visits, hospital admissions, and death. This disease predominantly affects small airways with acute inflammatory edema epithelial cells, excess mucus production, and bronchospasm. The most commonly involved organisms are Respiratory Syncytial Virus (accounting for 60% of cases), followed by Rhinovirus, Parainfluenza, Metapneumovirus, Influenza, and Adenovirus. Certain factors are associated with a higher risk of severe bronchiolitis, such as prematurity, chronic lung disease, cardiac disease, immunodeficiency, neuromuscular disease, and Down syndrome.
Diagnosis of bronchiolitis relies on a constellation of clinical manifestations, including respiratory distress and wheezing preceded by viral upper respiratory tract prodrome in children under two years of age. Common manifestations of bronchiolitis are rhinorrhea, cough, wheezing, tachypnea, and increased work of breathing, including nasal flaring, retractions, and grunting. Management of bronchiolitis is mainly supportive, aiming at maintaining adequate oxygenation and hydration.
Given the high burden of bronchiolitis and the lack of specific treatment, studies have investigated several therapeutic options. One of these potential therapies is vitamin D. Vitamin D is a fat-soluble vitamin that is mainly formed in the skin after exposure to ultraviolet rays, while less than 10% is obtained from dietary sources. Besides regulation of calcium and phosphorus homeostasis, vitamin D plays an important role in enhancing mucosal immune defense, decreasing excessive inflammation, and increasing mucociliary clearance. Vitamin D deficiency is common among children, particularly in developing countries, and has been linked to an increased risk of several diseases, including bronchiolitis, pneumonia, and otitis media.
Experimental studies have shown that vitamin D reduces inflammation of epithelial cells in airways infected with Respiratory Syncytial Virus and confers antiviral effects. Furthermore, several studies have shown lower serum vitamin D levels in hospitalized children with bronchiolitis. However, studies on the efficacy of Vitamin D supplementation for children with bronchiolitis are scarce with inconsistent findings.
In this study, we aim to evaluate the efficacy of vitamin D supplementation in children with bronchiolitis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study group | Experimental | Children receive a single dose of intramuscular 200,000 IU vitamin D3 |
|
| Control group | No Intervention | Children receiving only the standard recommended dose of vitamin D3 as 400 IU/day orally |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D3 | Drug | A single dose of intramuscular 200,000 IU vitamin D3 within 24 hours of admission |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time from randomization to discharge | Time from randomization to hospital discharge (in hours) | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time from randomization to discontinuation of oxygen therapy | Time from randomization to discontinuation of oxygen therapy (in hours) | 4 weeks |
| Time from randomization to discontinuation of intravenous fluids |
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Inclusion Criteria:
Exclusion Criteria:
.• History of previous episodes of wheezing.
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| Name | Affiliation | Role |
|---|---|---|
| Mostafa A Mohammed, MD, PhD | Sohag University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sohag University Hospital | Sohag | 82524 | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36765418 | Background | Manti S, Staiano A, Orfeo L, Midulla F, Marseglia GL, Ghizzi C, Zampogna S, Carnielli VP, Favilli S, Ruggieri M, Perri D, Di Mauro G, Gattinara GC, D'Avino A, Becherucci P, Prete A, Zampino G, Lanari M, Biban P, Manzoni P, Esposito S, Corsello G, Baraldi E. UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants. Ital J Pediatr. 2023 Feb 10;49(1):19. doi: 10.1186/s13052-022-01392-6. | |
| 25349312 |
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Unidentified patients' data will be available upon reasonable request after publication
After publication of the study
Unidentified patients' data will be available upon reasonable request after publication
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Nov 5, 2024 | |
| Reset | Dec 23, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Nov 5, 2024 | Dec 23, 2024 |
| ID | Term |
|---|---|
| D001988 | Bronchiolitis |
| ID | Term |
|---|---|
| D001991 | Bronchitis |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
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Not provided
| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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Two groups of children with bronchiolitis:
Study group: will receive a single dose of intramuscular 200,000 IU vitamin D3 within 24 hours of admission.
Control group: will receive the standard recommended dose of vitamin D3 as 400 IU/day orally
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Time from randomization to discontinuation of intravenous fluids (in hours)
| 4 weeks |
| Time from randomization to meeting discharge criteria | Time from randomization to meeting hospital discharge criteria (in hours) | 4 weeks |
| Time from hospital admission to discharge | Time from hospital admission to discharge (in hours) | 4 weeks |
| Blood level of 25-hydroxycholecalciferol | Blood level of 25-hydroxycholecalciferol | On day 3 after randomization |
| Serum level of ionized calcium | Serum level of ionized calcium | On day 3 after randomization |
| Admission to pediatric intensive care unit | Proportion of patients admitted to pediatric intensive care unit | 4 weeks |
| Intubation | Proportion of patients who underwent endotracheal intubation | 4 weeks |
| Mortality | Proportion of patients who died during hospital admission | 4 weeks |
| Bronchodilator therapy | Proportion of patients who received bronchodilator therapy | 4 weeks |
| Systemic steroids | Proportion of patients who received systemic steroids | 4 weeks |
| Background |
| Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ, Zorc JJ, Stanko-Lopp D, Brown MA, Nathanson I, Rosenblum E, Sayles S 3rd, Hernandez-Cancio S; American Academy of Pediatrics. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014 Nov;134(5):e1474-502. doi: 10.1542/peds.2014-2742. |
| 26745253 | Background | Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Makitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Savendahl L, Khadgawat R, Pludowski P, Maddock J, Hypponen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Hogler W. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016 Feb;101(2):394-415. doi: 10.1210/jc.2015-2175. Epub 2016 Jan 8. |
| 26521023 | Background | Esposito S, Lelii M. Vitamin D and respiratory tract infections in childhood. BMC Infect Dis. 2015 Oct 28;15:487. doi: 10.1186/s12879-015-1196-1. |
| 33931018 | Background | Golan-Tripto I, Loewenthal N, Tal A, Dizitzer Y, Baumfeld Y, Goldbart A. Vitamin D deficiency in children with acute bronchiolitis: a prospective cross-sectional case- control study. BMC Pediatr. 2021 Apr 30;21(1):211. doi: 10.1186/s12887-021-02666-4. |
| 35692038 | Background | Khoshnevisasl P, Sadeghzadeh M, Kamali K, Ardalani A. A randomized clinical trial to assess the effect of zinc and vitamin D supplementation in addition to hypertonic saline on treatment of acute bronchiolitis. BMC Infect Dis. 2022 Jun 13;22(1):538. doi: 10.1186/s12879-022-07492-2. |
| 1731571 | Background | Wang EE, Milner RA, Navas L, Maj H. Observer agreement for respiratory signs and oximetry in infants hospitalized with lower respiratory infections. Am Rev Respir Dis. 1992 Jan;145(1):106-9. doi: 10.1164/ajrccm/145.1.106. |
| 35420658 | Background | Brustad N, Yousef S, Stokholm J, Bonnelykke K, Bisgaard H, Chawes BL. Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Apr 1;5(4):e227410. doi: 10.1001/jamanetworkopen.2022.7410. |
| Background | Sarhan AA, Saeed NM, Mostafa AA, Osman AM. Vitamin D supplementation for acute bronchiolitis: a double-blind randomized controlled trial. Alexandria Journal of Pediatrics. 2019;32(2):61. |
| Background | Saad K, Abd Aziz NH, El-Houfey AA, El-Asheer O, Mohamed SA, Ahmed AE, Abdel Baseer KA, Darwish MM. Trial of vitamin D supplementation in infants with bronchiolitis: a randomized, double-blind, placebo-controlled study. Pediatric Allergy, Immunology, and Pulmonology. 2015;28(2):102-6 |
| D012140 |
| Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |