Lower respiratory tract infections are a major
cause of mortality in children below the age of five years, particularly
in resource-poor countries. Although advances in treatment protocols
have reduced mortality rates, and improved vaccine technology has seen
the development of more effective vaccines against a number of pathogens
such as Streptococcus pneumoniae, the costs involved may prohibit
their introduction in those countries most in need. Thus cheaper
alternatives to boost infants’ and young children’s resistance to
respiratory infections, and to reduce the severity of the disease when
it occurs, are urgently needed. Over the last 20 years, the role of
vitamin D in modulating the immune response to infection has generated
considerable interest. The ability of vitamin D to enhance innate
immunity through its role in stimulating the production of a number of
antibacterial proteins, such as cathelicidin and defensins, and
autophagosomes by activated monocytes and macrophages is well documented
[1]. Vitamin D also has a role in adaptive immunity reducing the acute
inflammatory response and increasing Th2 lymphocytes. A number of
studies have highlighted the association between vitamin D
deficiency/rickets and acute lower respiratory tract
infections/pneumonia [2,3]; and in case-control studies, 25(OH)D levels
have been found to be lower in cases with respiratory infections than
controls [4], but it is unclear if improving the vitamin D status of
infants will reduce the severity of the disease. Although it is possible
that the observed association between rickets and pneumonia reflects the
impaired immune response accompanying vitamin D deficiency, it is also
possible that mechanical factors such as more pliable ribs associated
with rickets and reduced ventilation and clearance of lung secretions
due to hypotonia might play major roles.
In a randomized controlled trial published in this
issue of Indian Pediatrics, Gupta and colleagues [5] were unable
to show a convincing evidence of positive biological effects of vitamin
D supplementation on either the response of severe pneumonia to
treatment or the prevention of recurrence over a six month period in
under-five children. Before one discards a possible positive effect of
vitamin D status on the response to therapy for severe pneumonia in
young children, it must be appreciated that in the present study vitamin
D supplementation only began at the time of the child’s hospitalization
with pneumonia; thus there was little time for supplementation to have
an effect on vitamin D status and thus on the enhancement of the speed
of resolution of the pneumonia. Few studies have assessed the
pharmacokinetics of a bolus of vitamin D in young children. Thacher and
colleagues [6] studied the change in serum 25(OH)D in groups of young
Nigerian children following an oral bolus of 50,000 IU vitamin D2 or D3.
Peak concentrations of 25(OH)D were found 3 days after bolus
administration, which is longer than the time taken for resolution of
the clinical features of severe pneumonia (median approximately 30
hours). The findings of Gupta, et al. [5] are in keeping with two
other studies which reported a lack of a therapeutic effect of acute
vitamin D supplementation on the rate of resolution of acute pneumonia
[7]. The second aspect of the study by Gupta, et al. [5] was to
assess the effect of vitamin D supplementation on the incidence of
recurrence of pneumonia over six months. Once again, no effect was
noted, but it is possible that the bolus of vitamin D was not given
frequently enough to maintain vitamin D sufficiency, as the difference
in 25(OH)D in the treatment group between admission and 3 months had
fallen to only 7 ng/mL compared to 30 ng/mL at two weeks. 25(OH)D
concentrations were not measured at 6 months after administration, but
it is likely that the placebo and study groups would have had very
similar levels. As mentioned by Gupta, et al. [5], these results
are at variance with those reported from Kabul [8], where recurrence of
pneumonia was reduced for three months following administration of
100,000 IU vitamin D. It is of interest to note that the same authors in
another study conducted in Kabul were unable to show an effect of
chronic vitamin D supplementation (100,000 IU vitamin D three monthly)
on the incidence of the first episode of pneumonia in infants and young
children [9].
Some studies suggest that current vitamin D status as
well as in utero vitamin D exposure may be inversely associated
with the incidence of asthma, wheeze and respiratory infections in young
children. A recent meta-analysis of 16 birth-cohort studies concluded
that increased in utero exposure to 25(OH)D reduced the risk of
asthma and wheezing, but not of respiratory tract infections in children
[10].
Thus, evidence for a beneficial effect of vitamin D
supplementation on the incidence of lower respiratory tract infections
remains inconclusive [11,12]. Until further supporting evidence is
available, pediatricians and other child health professionals should
increase their efforts to prevent vitamin D deficiency during pregnancy
and eradicate rickets during infancy and childhood through ensuring
adequate vitamin D status during pregnancy and universal vitamin D
supplementation of infants less than 12 months of age, as is currently
recommended in a global consensus statement [13].
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2. Muhe L, Luiseged S, Mason KE, Simoes EAF.
Case-control study of the role of nutritional rickets in the risk of
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3. Larkin A, Lassetter J. Vitamin D deficiency and
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Schinnar R, Strom BL. Children with lower respiratory tract infections
and serum 25-hydroxyvitamin D3 levels: A case-control study. Pediatr
Pulmonol. 2016;51:1080-7.
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IR, et al. Vitamin D supplementation for treatment and prevention
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controlled trial. Indian Pediatr. 2016;53:967-76.
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children with nutritional rickets. J Bone Miner Res. 2010;25:1988-95.
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Masher MI, Bhutta ZA, et al. Effect on the incidence of pneumonia
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10. Feng H, Xun P, Pike K, Wills AK, Chawes BL,
Bisgaard H, et al. In utero exposure to 25(OH) D and risk of
childhood asthma, wheeze and respiratory tract infections: a
meta-analysis of birth cohort studies. J Allergy Clin Immunol. 2016 (in
press)
11. Esposito S, Lelii M. Vitamin D and respiratory
tract infections in childhood. BMC Infect Dis. 2015;15:487.
12. Ali SR, McDevitt H. Question 1: Does vitamin D
supplementation prevent acute lower respiratory tract infections in
children? Arch Dis Child. 2015;100:892-5.
13. Munns CF, Shaw N, Kiely M, Specker BL, Thacher
TD, Ozono K, et al. Global Consensus Recommendations on
prevention and management of nutritional rickets. J Clin Endocrinol
Metab. 2016;101:394-415.