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Published in: Trials 1/2016

Open Access 01-12-2016 | Research

Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial

Authors: Megan E. Jensen, Genevieve Mailhot, Nathalie Alos, Elizabeth Rousseau, John H. White, Ali Khamessan, Francine M. Ducharme

Published in: Trials | Issue 1/2016

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Abstract

Background

Trials in school-aged children suggest vitamin D supplementation reduces asthma exacerbations. Primary aim: to examine whether vitamin D3 (100,000 IU) rapidly raises serum 25-hydroxyvitamin D (25OHD) ≥75 nmol/L in asthmatic preschoolers.

Methods

In a double-blind, randomised, placebo-controlled trial, preschool-aged children with asthma received 100,000 IU vitamin D3 (intervention) or placebo (control), followed by 400 IU vitamin D3 daily for 6 months. Serum 25OHD was measured at baseline, 10 days, 3 and 6 months. Outcomes included the group difference in 25OHD change from baseline at 3 months (Δ25OHD); the proportion of children with 25OHD ≥75 nmol/L at 3 months; the pattern in serum vitamin D over 6 months; the proportion of children with hypercalciuria at any time point (safety); and group rates for oral corticosteroids. Continuous outcomes were analysed using generalised linear mixed models and group rate ratios of events per child were assessed using a Poisson distribution model.

Results

Twenty-two children were randomised (intervention:11; control:11) during winter. At 3 months, the group difference in Δ25OHD (7.2 nmol/L; 95 % CI: -13.7, 28.1) was not significant; yet, 100 % versus 54.5 % (intervention versus control) had serum 25OHD ≥75 nmol/L. There was a significant group difference in Δ25OHD at 10 days (110.3 nmol/L; 95 % CI: 64.0, 156.6). One child in each group had transient hypercalciuria at 10 days. Group oral corticosteroids rates were 0.82 and 1.18/child, intervention versus control (rate ratio = 0.68; 95 % CI: 0.30, 1.62; non-significant).

Conclusions

Following 100,000 IU vitamin D3, all children reached serum 25OHD ≥75 nmol/L, compared with half who received placebo. Daily supplementation, sun exposure and insufficient power may explain the absence of a significant 3-month group difference in Δ25OHD. No clinically important alterations in bone metabolism biomarkers occurred. Group oral corticosteroid rates will inform sample size calculations for the larger trial. (NCT01999907, 25 November 2013).
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Literature
1.
Rosychuk RJ, Voaklander DC, Klassen TP, Senthilselvan A, Marrie TJ, Rowe BH. Asthma presentations by children to emergency departments in a Canadian province: a population-based study. Pediatr Pulmonol. 2010;45:985–92.CrossRefPubMed
2.
Lougheed MD, Garvey N, Chapman KR, Cicutto L, Dales R, Day AG, et al. The Ontario Asthma Regional Variation Study: emergency department visit rates and the relation to hospitalization rates. Chest. 2006;129:909–17.CrossRefPubMed
3.
4.
Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995;332:133–8.CrossRefPubMed
5.
Xepapadaki P, Papadopoulos NG. Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers. Eur Respir J. 2010;36:438–45.CrossRefPubMed
6.
Bacharier LB, Phillips BR, Zeiger RS, Szefler SJ, Martinez FD, Lemanske Jr RF, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122:1127–35.CrossRefPubMedPubMedCentral
7.
Ducharme FM, Lemire C, Noya FJ, Davis GM, Alos N, Leblond H, et al. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med. 2009;360:339–53.CrossRefPubMed
8.
Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics. 2009;123:e519–25.CrossRefPubMed
9.
Ducharme FM, Tse SM, Chauhan B. Diagnosis, management, and prognosis of preschool wheeze. Lancet. 2014;383:1593–604.CrossRefPubMed
10.
Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, et al. Relationship between serum vitamin D, disease severity and airway remodeling in children with asthma. Am J Respir Crit Care Med. 2011;184:1342–9.CrossRefPubMedPubMedCentral
11.
Brehm JM, Schuemann B, Fuhlbrigge AL, Hollis BW, Strunk RC, Zeiger RS, et al. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010;126:52–8.CrossRefPubMedPubMedCentral
12.
Searing DA, Zhang Y, Murphy JR, Hauk PJ, Goleva E, Leung DYM. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. J Allergy Clin Immunol. 2010;125:995–1000.CrossRefPubMedPubMedCentral
13.
Science M, Maguire JL, Russell ML, Smieja M, Walter SD, Loeb M. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013;57:392–7.CrossRefPubMedPubMedCentral
14.
Majak P, Olszoweic-Chlebna M, Smejda K, Stelmach I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127:1294–6.CrossRefPubMed
15.
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010;91:1255–60.CrossRefPubMed
16.
Yadav M, Mittal K. Effect of vitamin D supplementation on moderate to severe bronchial asthma. Indian J Pediatr. 2014;81:650–4.CrossRefPubMed
17.
18.
Godel JC, Canadian Paediatric Society, First Nations, Inuit and Metis Health Committee. Vitamin D supplementation: recommendations for Canadian mothers and infants. Paediatr Child Health. 2007;12:583–9.
19.
Ducharme FM, Dell S, Radhakrishnan D, Grad R, Watson WM, Yang CM, et al. Diagnosis and management of asthma in preschoolers: a Canadian Thoracic Society and Canadian Pediatric Society position paper. Can Respir J. 2015;22:135–43.CrossRefPubMedPubMedCentral
20.
Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermat. 1988;124:869–71.CrossRef
21.
Ducharme FM, Davis GM, Noya F, Rich H, Ernst P. The Asthma Quiz for Kidz: a validated tool to appreciate the level of asthma control in children. Can Respir J. 2004;11:541–6.CrossRefPubMed
22.
van den Ouweland JM, Vogeser M, Bacher S. Vitamin D and metabolites measurement by tandem mass spectrometry. Rev Endocr Metab Disord. 2013;14:159–84.CrossRefPubMed
23.
Raymond F, Carbonneau J, Boucher N, Robitaille L, Boisvert S, Wu WK, et al. Comparison of automated microarray detection with real-time PCR assays for detection of respiratory viruses in specimens obtained from children. J Clin Microbiol. 2009;47:743–50.CrossRefPubMedPubMedCentral
24.
Jacobs B. The Canadian Acute Respiratory Illness and Flu Scale (CARIFS): the design and assessment of a paediatric disease severity measure. (Thesis) Toronto: Toronto: University of Toronto; 1999.
25.
Ducharme FM, Jensen ME, Mendelson M, Parkin P, Desplats E, Zhang X, et al. Asthma Flare-up Diary for Young Children (ADYC) to monitor severity of exacerbations. J Allergy Clin Immunol. 2016;137:744–9.CrossRefPubMed
26.
Jensen ME, Mendelson MJ, Desplats E, Zhang X, Platt R, Ducharme FM. Caregiver’s functional status during a young child’s asthma exacerbation: a validated instrument. J Allergy Clin Immunol. 2016;137:782–8.CrossRefPubMed
27.
Metz MP. Determining urinary calcium/creatinine cut-offs for the paediatric population using published data. Ann Clinic Biochem. 2006;43:398–401.CrossRef
28.
Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA, et al. Closing the gaps in pediatric laboratory reference intervals: a caliper database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012;58:854–68.CrossRefPubMed
29.
Gallo S, Comeau K, Vanstone C, Agellon S, Sharma A, Jones G, et al. Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial. JAMA. 2013;309:1785–92.CrossRefPubMed
30.
IOM (Institute of Medicine). Dietary reference intakes for calcium and vitamin D. Washington DC: The National Academies Press; 2011.
31.
Zeghoud F, Ben-Mekhbi H, Djeghri N, Garabédian M. Vitamin D prophylaxis during infancy: comparison of the long-term effects of three intermittent doses (15, 5, or 2.5 mg) on 25-hydroxyvitamin D concentrations. Am J Clin Nutr. 1994;60:393–6.PubMed
32.
Mallet E, Philippe F, Castanet M, Basuyau JP. Administration of a single winter oral dose of 200,000 IU of vitamin D3 in adolescents in Normandy: evaluation of the safety and vitamin D status obtained. Arch Pediatr. 2010;17:1042–6.CrossRefPubMed
33.
Oliveri B, Cassinelli H, Mautalen C, Ayala M. Vitamin D prophylaxis in children with a single dose of 150000 IU of vitamin D. Eur J Clin Nutr. 1996;50:807–10.PubMed
34.
Arpadi SM, McMahon D, Abrams EJ, Bamji M, Purswani M, Engelson ES, et al. Effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents. Pediatrics. 2009;123:e121–6.CrossRefPubMedPubMedCentral
35.
Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA, et al. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet. 2012;379:1419–27.CrossRefPubMedPubMedCentral
36.
Manaseki-Holland S, Qader G, Isaq Masher M, Bruce J, Zulf Mughal M, Chandramohan D, et al. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health. 2010;15:1148–55.CrossRefPubMed
37.
Tau C, Ciriani V, Scaiola E, Acuna M. Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra del Fuego, Argentina. J Steroid Biochem Mol Bio. 2007;103:651–4.CrossRef
38.
Vidailhet M, Mallet E, Bocquet A, Bresson JL, Briend A, Chouraqui JP, et al. Vitamin D: still a topical matter in children and adolescents. A position paper by the Committee on Nutrition of the French Society of Paediatrics. Arch Pediatr. 2012;19:316–28.CrossRefPubMed
39.
Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173:2909–12.CrossRefPubMed
40.
Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3: a helpful immuno-modulator. Immunol. 2011;134:123–39.CrossRef
41.
Bosse Y, Maghni K, Hudson TJ. 1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes. Physiol Genomics. 2007;29:161–8.CrossRefPubMed
42.
Zitterman A, Pilz S, Hoffman H, Marz W. Vitamin D and airway infections: a European perspective. Eur J Med Res. 2016;21:14.CrossRef
43.
Vieth R. How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology. Anticancer Res. 2009;29:3675–84.PubMed
44.
Upham JW, Sly PD. Vitamin D in asthma. Is the golden bullet losing its luster? Am J Resp Crit Care Med. 2016;193:598–600.CrossRefPubMed
45.
Ducharme FM, Morin J, Davis GM, Gingras J, Noya FJ. High physician adherence to phenotype-specific asthma guidelines, but large variability in phenotype assessment in children. Curr Med Res Opin. 2012;28:1561–70.CrossRefPubMed
46.
Schultz A, Brand PLP. Episodic viral wheeze and multiple trigger wheeze in preschool children: a useful distinction for clinicians? Paed Respir Rev. 2011;12:160–4.
Metadata
Title
Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial
Authors
Megan E. Jensen
Genevieve Mailhot
Nathalie Alos
Elizabeth Rousseau
John H. White
Ali Khamessan
Francine M. Ducharme
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1483-1

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