Vitamin D and respiratory tract infections in childhood

Susanna Esposito, Mara Lelii, Susanna Esposito, Mara Lelii

Abstract

Background: Respiratory tract infections (RTIs) remain among of the most important causes of morbidity and mortality among children. Several studies have associated vitamin D deficiency with an increased risk of RTIs, and vitamin D supplementation has been proposed as a possible preventive measure against RTIs in children. The main aim of this review is to summarize the current evidence from the literature about the link between vitamin D and RTIs in children.

Discussion: Several recent studies have shown that vitamin D has different immunomodulatory properties associated with the risk of RTIs in childhood. In this regard, it is very important to understand the definition of deficiency and insufficiency of vitamin D and when and how to treat this condition. Unfortunately, there is no consensus, although a level of at least 10 ng/mL 25-hydroxycholecalciferol (25[OH]D) is thought to be necessary to promote bone mineralization and calcium homeostasis, and a concentration between 20 ng/mL and 50 ng/mL is considered adequate to provide an immunomodulatory effect. Available data support a role for vitamin D deficiency in the risk of pediatric tuberculosis, recurrent acute otitis media, and severe bronchiolitis, whereas further studies are needed to confirm an association in children with recurrent pharyngotonsillitis, acute rhinosinusitis and community-acquired pneumonia.

Conclusions: Maintenance of adequate vitamin D status may be an effective and inexpensive prophylactic method against some RTIs, but the supplementation regimen has not been clearly defined. Further clinical trials are needed to determine the 25(OH)D concentrations associated with an increased risk of RTIs and optimal vitamin D supplementation regimen according to the type of RTI while also taking into consideration vitamin D receptor polymorphisms.

References

    1. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80(Suppl. 6):1678S–88.
    1. Norman AW, Bouillon R, Whiting SJ, Vieth R, Lips P. 13th Workshop consensus for vitamin D nutritional guidelines. J Steroid Biochem Mol Biol. 2007;103:204–5. doi: 10.1016/j.jsbmb.2006.12.071.
    1. Holick MF. Phylogenetic and evolutionary aspects of vitamin D from phyoplankon to humans. In: Pang PKT, Schreibman MP, editors. Vertebrate endocrinology: fundamentals and biomedical implications. Orlando, FL: Academic; 1989. pp. 7–43.
    1. Palm TA. The geographical distribution and aetiology of rickets. Practitioner. 1890;14:270–342.
    1. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116:2062–72. doi: 10.1172/JCI29449.
    1. Rajakumar K, Greenspan SL, Thomas SB, Holick MF. Solar ultraviolet radiation and vitamin D: A historical perspective. Am J Pub Health. 2007;97:1746–54. doi: 10.2105/AJPH.2006.091736.
    1. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169:551–61. doi: 10.1001/archinternmed.2008.600.
    1. Holick MF. Vitamin D: a millennium perspective. J Cell Biochem. 2003;88:296–307. doi: 10.1002/jcb.10338.
    1. Zittermann A, Gummert JF. Nonclassical vitamin D actions. Nutrients. 2010;2:408–25. doi: 10.3390/nu2040408.
    1. Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamäki H, et al. An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86:714–7.
    1. Ginde AA, Mansbach JM, Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169:384–90. doi: 10.1001/archinternmed.2008.560.
    1. Esposito S, Baggi E, Bianchini S, Marchisio P, Principi N. Role of vitamin D in children with respiratory tract infections. Int J Immunopathol Pharmacol. 2013;26:1–13.
    1. Marchisio P, Nazzari E, Torretta S, Esposito S, Principi N. Medical prevention of recurrent acute otitis media: an updated overview. Expert Rev Anti Infect Ther. 2014;12:611–20. doi: 10.1586/14787210.2014.899902.
    1. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008;88:491S–9. doi: 10.3945/ajcn.2008.27049.
    1. Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982;1:74–6. doi: 10.1016/S0140-6736(82)90214-8.
    1. Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw W, Shany J. Evidence for alteration of the vitamin D endocrine system in blacks. J Pediatr. 1985;76:470–3.
    1. Holick MF. Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr. 1995;61(Suppl. 3):638S–45.
    1. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin Dı synthesis in human skin. J Clin Endocrinol Metab. 1988;67:373–8. doi: 10.1210/jcem-67-2-373.
    1. Holick MF. Vitamin D requirements for the elderly. Clin Nutr. 1986;5:121–9.
    1. Clemens TL, Zhou X, Myles M, Endres D, Lindsay R. Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects. J Clin Endocrinol Metab. 1986;63:656–60. doi: 10.1210/jcem-63-3-656.
    1. Stamp TC, Haddad JG, Twigg CA. Comparison of oral 25-hydroxycholecalciferol, vitamin D, and ultraviolet light as determinants of circulating 25-hydroxyvitamin D. Lancet. 1977;1:1341–3. doi: 10.1016/S0140-6736(77)92553-3.
    1. Holick MF, Schnoes HK, De Luca HF, Suda T, Cousins RJ. Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry. 1971;10:2799–804. doi: 10.1021/bi00790a023.
    1. Antoniucci DM, Yamashita T, Portaloe AA. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab. 2006;91:3144–9. doi: 10.1210/jc.2006-0021.
    1. Hewison M, Burke F, Evans KN, Lammas DA. Extra-renal 25-hydroxyvitamin D3-1alphahydroxylase in human health and disease. J Steroid Biochem Mol Biol. 2007;103:316–21. doi: 10.1016/j.jsbmb.2006.12.078.
    1. Gray TK, Lester GE, Lorenc RS. Evidence for extra-renal 1α-hydroxylation of 25-hydroxyvitamin D3 in pregnancy. Science. 1979;204:1311–3. doi: 10.1126/science.451538.
    1. Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL. Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D. N Engl J Med. 1981;305:440–3. doi: 10.1056/NEJM198108203050807.
    1. Haderslev KV, Jeppesen PB, Sorensen HA, Mortensen PB, Staun M. Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection. Gut. 2003;52:653–8. doi: 10.1136/gut.52.5.653.
    1. Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008;4:404–12. doi: 10.1038/ncprheum0855.
    1. Thomasset M. Vitamin D and the immune system. Phatol Bio. 1994;42:163–72.
    1. Veldman CM, Cantorna MT, De Luca HF. Expression of 1,25 dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys. 2000;374:334–8. doi: 10.1006/abbi.1999.1605.
    1. Miyamoto K, Kesterson RA, Yamamoto H, Taketani Y, Nishiwaki E, Tatsumi S, et al. Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol. 1997;11:1165–79. doi: 10.1210/mend.11.8.9951.
    1. Jurutka PW, Whitfield GK, Hsieh JC, Thompson PD, Haussler CA, Haussler MR. Molecular nature of the vitamin D receptor and its role in regulation of gene expression. Rev Endocr Metab Disord. 2002;2:203–16. doi: 10.1023/A:1010062929140.
    1. Haussler MR, Whitfield GK, Haussler CA, Hsier JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res. 1998;13:325–49. doi: 10.1359/jbmr.1998.13.3.325.
    1. Labuda M, Fujiwara TM, Ross MV, Morgan K, Garcia-Heras J, Ledbetter DH, et al. Two hereditary defects related to vitamin D metabolism map to the same region of human chromosome 12q13–14. J Bone Miner Res. 1992;7:1447–53. doi: 10.1002/jbmr.5650071212.
    1. Uitterlinden AG, Fang Y, Van Meurs JBJ, Pols HAP, JPTM V l. Genetics and biology of vitamin D receptor polymorphism. J Steroid Biochem Mol Biol. 2004;89–90:187–93. doi: 10.1016/j.jsbmb.2004.03.083.
    1. Van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;97:93–101. doi: 10.1016/j.jsbmb.2005.06.002.
    1. Lemire JM, Archer DC, Beck L, Spielberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: prefential inhibitions of Th1 functions. J Nutr. 1995;125:1704–8.
    1. Underwood MA, Bevins CL. Defensin-barbed innate immunity: clinical associations in the pediatric population. Pediatrics. 2010;125:1237–47. doi: 10.1542/peds.2009-3289.
    1. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3: A helpful immuno-modulator. Immunology. 2011;134:123–39. doi: 10.1111/j.1365-2567.2011.03482.x.
    1. D’Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, et al. Inibition of IL-12 production by 1,25-dihydroxyvitamin D3 involvement of NfkB downregulation in transcriptional repression of the p40 gene. J Clin Invest. 1998;101:252–62. doi: 10.1172/JCI1050.
    1. Hakim I, Bar-Shavit Z. Modulation of TNF-alpha expression in bone marrow macrophages: involvement of vitamin D response element. J Cell Biochem. 2003;88:986–98. doi: 10.1002/jcb.10453.
    1. Ryynänen J, Carlberg C. Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells. Plos One. 2013;8:e78170. doi: 10.1371/journal.pone.0078170.
    1. Mahon BD, Wittke A, Weaver V, Cantorna MT. The targets of vitamin D depend on the differentiation and activation status of CD4-positive T-cells. J Cell Biochem. 2003;89:922–32. doi: 10.1002/jcb.10580.
    1. Sun J. Vitamin D and mucosal immune function. Curr Opin Gastroenterol. 2010;26:591–5. doi: 10.1097/MOG.0b013e32833d4b9f.
    1. Bansal AS, Henriquez F, Sumar N, Patel S. T helper cell subsets in arthritis and the benefits of immunomodulation by 1,25(OH)2 vitamin D. Rheumatol Int. 2012;32:845–52. doi: 10.1007/s00296-011-2077-6.
    1. Al-Daghri NM, Guerini FR, Al-Attas OS, Alokail MS, Alkharfy KM, Draz HM, et al. Vitamin D receptor gene polymorphisms are associated with obesity and inflammosome activity. Plos One. 2014;9:e102141. doi: 10.1371/journal.pone.0102141.
    1. Shaw NJ, Mughal Z. Vitamin D and child health (extra skeletal aspects) Arch Di Child. 2013;98:368–72. doi: 10.1136/archdischild-2012-302585.
    1. Hewison M. Vitamin D and innate and adaptive immunity. Vitam Horm. 2011;86:23–62. doi: 10.1016/B978-0-12-386960-9.00002-2.
    1. Esposito S, Rigante D, Principi N. Do children’s upper respiratory tract infections benefit from probiotics? BMC Infect Dis. 2014;14:194. doi: 10.1186/1471-2334-14-194.
    1. Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in children. Lancet. 2005;365:1147–52. doi: 10.1016/S0140-6736(05)71877-8.
    1. Najada AS, Habashneh MS, Khader M. The frequency of nutritional rickets among hospitalized infants and its relation to respiratory diseases. J Trop Pediatr. 2004;50:364–8. doi: 10.1093/tropej/50.6.364.
    1. Williams B, Williams AJ, Anderson ST. Vitamin D deficiency and insufficiency in children with tuberculosis. Pediatr Infect Dis J. 2008;27:391–6. doi: 10.1097/INF.0b013e31817525df.
    1. Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case–control study. Lancet. 2000;355:618–21. doi: 10.1016/S0140-6736(99)02301-6.
    1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:S1080–6.
    1. Esposito S, Baggi E, Bianchini S, Principi N. Implications of maternal vitamin D deficiency for the fetus, the neonate and the young infant. Eur J Nutr. 2013;52:859–67. doi: 10.1007/s00394-012-0476-4.
    1. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37:113–9. doi: 10.1093/ije/dym247.
    1. Rios M, Garcıa JM, Sanchez JA, Perez D. A statistical analysis of the seasonality in pulmonary tuberculosis. Eur J Epidemiol. 2000;16:483–8. doi: 10.1023/A:1007653329972.
    1. Schaaf HS, Nel ED, Beyers N, Gie RP, Scott F, Donald P. A decade of experience with Mycobacterium tuberculosis culture from children: a seasonal influence on incidence of childhood tuberculosis. Tuber Lung Dis. 1996;77:43–6. doi: 10.1016/S0962-8479(96)90074-X.
    1. Rockett KA, Brookes R, Udalova I, Vidal V, Hill AV, Kwiatkowski D. 1,25-Dihydroxyvitamin D3induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun. 1998;66:5314–21.
    1. Sly LM, Lopez M, Nauseef WM, Reiner NE. 1alpha,25-Dihydroxyvitamin D3-induced monocyte antimycobacterial activity is regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent phagocyte oxidase. J Biol Chem. 2001;276:35482–93. doi: 10.1074/jbc.M102876200.
    1. Coussens A, Timms PM, Boucher BJ, Venton TR, Ashcroft AT, Skolimowska KH, et al. 1-alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection. Immunology. 2009;127:539–48. doi: 10.1111/j.1365-2567.2008.03024.x.
    1. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–3. doi: 10.1126/science.1123933.
    1. Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN- {gamma}- and TNF-independent vitamin D-inducible human suppression of Mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007;178:7190–8. doi: 10.4049/jimmunol.178.11.7190.
    1. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009;6:231–43. doi: 10.1016/j.chom.2009.08.004.
    1. Selvaraj P, Chandra G, Jawahar MS, Rani MV, Rajeshwari DN, Narayanan PR. Regulatory role of vitamin D receptor gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on macrophage phagocytosis and lymphoproliferative response to mycobacterium tuberculosis antigen in pulmonary tuberculosis. J Clin Immunol. 2004;24:523–32. doi: 10.1023/B:JOCI.0000040923.07879.31.
    1. Roth DE, Soto G, Arenas F, Bautista CT, Ortiz J, Rodriguez R, et al. Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis. J Infect Dis. 2004;190:920–7. doi: 10.1086/423212.
    1. Davies PDO, Nisar M. Racial differences of Mycobacterium tuberculosis infection. N Engl J Med. 1990;322:1672.
    1. Davies PDO. A possible link between vitamin D deficiency and impaired host defence to Mycobacterium tuberculosis. Tubercle. 1985;66:301–6. doi: 10.1016/0041-3879(85)90068-6.
    1. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011;377:242–50. doi: 10.1016/S0140-6736(10)61889-2.
    1. Rathored J, Sharma SK, Singh B, Banavaliker JN, Sreenivas V, Srivastava AK, et al. Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D. Int J Tuberc Lung Dis. 2012;16:1522–8. doi: 10.5588/ijtld.12.0122.
    1. Gray K, Wood N, Gunasekera H, Sheikh M, Hazelton B, Barzi F, et al. Vitamin D and tubercolosis status in refugee children. Pediatr Infect Dis J. 2012;31:521–3. doi: 10.1097/INF.0b013e3182456c55.
    1. Gianmaa D, Giovannucci E, Bloom BR, Fawzi W, Burr W, Batbaatar D, et al. Vitamin D, tuberculin skin test conversion, and latent tubercolosis in Mongolian school-age children: a randomized, double-blind, placebo- controlled feasibility trial. Am J Clin Nutr. 2012;96:391–6. doi: 10.3945/ajcn.112.034967.
    1. Venturini E, Facchini L, Martinez-Alier N, Novelli V, Galli L, de Martino M, et al. Vitamin D and tuberculosis: a multicenter study in children. BMC Infect Dis. 2014;14:652. doi: 10.1186/s12879-014-0652-7.
    1. Khandelwal D, Gupta N, Mukherjee A, Lodha R, Singh V, Grewal HM, et al. Vitamin D levels in Indian children with intrathoracic tuberculosis. Indian J Med Res. 2014;140:531–7.
    1. Morcos MM, Gabr AA, Samuel S, Kamel M, el Baz M, el Beshry M, et al. Vitamin D administration to tuberculous children and its value. Boll Chim Farm. 1998;137:157–64.
    1. Teele D, Klein J, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J Infect Dis. 1989;160:83–94. doi: 10.1093/infdis/160.1.83.
    1. Paradise JL, Rockette HE, Colborn DK, Bernard BS, Smith CG, Kurs-Lasky M, et al. Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two year of life. Pediatrics. 1997;99:318–33. doi: 10.1542/peds.99.3.318.
    1. Greenberg D, Bilenko N, Liss Z. The burden of acute otitis media on the patient and family. Eur J Pediatr. 2003;162:576–81. doi: 10.1007/s00431-003-1260-5.
    1. Marchisio P, Nazzari E, Torretta S, Esposito S, Principi N. Medical prevention of recurrent acute otitis media: an updated overview. Expert Rev Anti Infect Ther. 2014;12:611–20. doi: 10.1586/14787210.2014.899902.
    1. Pappas DE, Owen Hendley J. Otitis media. A scholarly review of the evidence. Minerva Pediatr. 2003;55:407.
    1. Gravel JS, Karma P, Casselbrant ML, Marchisio P, Andalibi A, Passali D, et al. Recent advances in otitis media. Diagnosis and screening. Ann Otol Rhinol Laryngol Suppl. 2005;194:104–13.
    1. Sun H, Tao Z, Li X, Fang J. The spontaneous otitis media in rickety rats. Hunan Yi Ke Da Xue Xue Bao. 1997;22:317–9.
    1. Thornton KA, Marin C, Mora-Plazas M, Villamor E. Vitamin D deficiency associated with increased incidence of gastrointestinal and ear infections in school-age children. Pediatr Infect Dis J. 2013;32:585–93. doi: 10.1097/INF.0b013e3182868989.
    1. Cayir A, Turan MI, Okzan O, Cayir Y. Vitamin D levels in children diagnosed with acute otitis media. J Park Med Assoc. 2014;64:1274–7.
    1. Marchisio P, Consonni D, Baggi E, Zampiero A, Bianchini S, Terranova L, et al. Vitamin D supplementation reduces the risk of acute otitis media in otitis-prone children. Pediatr Infect Dis J. 2013;32:1055–60. doi: 10.1097/INF.0b013e31829be0b0.
    1. Cayir A, Turan MI, Ozkan O, Cayir Y, Kaya A, Davutoglu S, et al. Serum vitamin D levels in children with recurrent otitis media. Eur Arch Otorhinolaryngol. 2014;271:689–93. doi: 10.1007/s00405-013-2455-7.
    1. Alan L, Bisno MD. Acute pharyngitis: etiology and diagnosis. Pediatrics. 1996;97:949–54.
    1. Armstrong GL, Pinner RW. Outpatient visits for infectious diseases in the United States, 1980 through 1996. Arch Intern Med. 1999;159:2531–6. doi: 10.1001/archinte.159.21.2531.
    1. ESCMID Sore Throat Guideline Group. Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, et al. Guideline for the management of acute sore throat. Clin Microbiol Infect. 2012;18(Suppl. 1):1–28.
    1. Paradise JL, Bluestone CD, Colborn DK, Bernard BS, Rockette HE, Kurs-Lasky M. Tonsillectomy and adenotonsillectomy for recurrent throat infection in moderately affected children. Pediatrics. 2002;110:7–15. doi: 10.1542/peds.110.1.7.
    1. Nazzari E, Torretta S, Pignataro L, Marchisio P, Esposito S. Role of biofilm in children with recurrent upper respiratory tract infections. Eur J Clin Microbiol Infect Dis. 2015;34:421–9. doi: 10.1007/s10096-014-2261-1.
    1. Reid D, Morton R, Salkeld L, Bartley J. Vitamin D and tonsil disease--preliminary observations. Int J Pediatr Otorhinolaryngol. 2011;75:261–4. doi: 10.1016/j.ijporl.2010.11.012.
    1. Aydın S, Aslan I, Yıldız I, Ağaçhan B, Toptaş B, Toprak S, et al. Vitamin D levels in children with recurrent tonsillitis. J Pediatr Otorhinolaryngol. 2011;75:364–7. doi: 10.1016/j.ijporl.2010.12.006.
    1. Yildiz I, Unuvar E, Zeybek U, Toptas B, Cacina C, Toprak S, et al. The role of vitamin D in children with recurrent tonsillopharyngitis. Ital J Pediatr. 2012;38:25. doi: 10.1186/1824-7288-38-25.
    1. Nseir W, Mograbi J, Abu-Rahmeh Z, Mahamid M, Abu-Elheja O, Shalata A. The association between vitamin D levels and recurrent group A streptococcal tonsillopharyngitis in adults. Int J Infect Dis. 2012;16:e735–8. doi: 10.1016/j.ijid.2012.05.1036.
    1. Esposito S, Marchisio P, Tenconi R, Tagliaferri L, Albertario G, Patria MF, et al. Diagnosis of acute rhinosinusitis. Pediatr Allergy Immunol. 2012;23(Suppl 22):17–9. doi: 10.1111/j.1399-3038.2012.01319.x.
    1. Mulligan JK, White DR, Wang EW, Sansoni SR, Moses H, Yawn RJ, et al. Vitamin D3 deficiency increases sinus mucosa dendritic cells in pediatric chronic rhinosinusitis with nasal polyps. Otolaryngol Head Neck Surg. 2012;147:773–81. doi: 10.1177/0194599812448852.
    1. Mulligan JK, Nagel W, O’Connell BP, Wentzel J, Atkinson C, Schlosser RJ. Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2014;134:342–9. doi: 10.1016/j.jaci.2014.01.039.
    1. Wang LF, Lee CH, Chien CY, Chen JY, Chiang FY, Tai CF. Serum 25-hydroxyvitamin D levels are lower in chronic rhinosinusitis with nasal polyposis and are correlated with disease severity in Taiwanese patients. Am J Rhinol Allergy. 2013;27:e162–5. doi: 10.2500/ajra.2013.27.3948.
    1. Schlosser RJ, Soler ZM, Schmedes GW, Storck K, Mulligan JK. Impact of vitamin D deficiency upon clinical presentation in nasal polyposis. Int Forum Allergy Rhinol. 2014;4:196–169. doi: 10.1002/alr.21274.
    1. Salimpour R. Rickets in Tehran. Arch Dis Child. 1975;50:63–5. doi: 10.1136/adc.50.1.63.
    1. Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr. 2004;58:563–7. doi: 10.1038/sj.ejcn.1601845.
    1. Charan J, Goyal JP, Saxena D, Yadav PJ. Vitamin D for prevention of respiratory tract infections: a systematic review and meta-analysis. Pharmacol Pharmacother. 2012;3:300–3. doi: 10.4103/0976-500X.103685.
    1. Mohamed WA, Al-Shehri MA. Cord blood 25-hydroxyvitamin D levels and the risk of acute lower respiratory tract infection in early childhood. J Trop Pediatr. 2013;59:29–35. doi: 10.1093/tropej/fms042.
    1. Dinlen N, Zenciroglu A, Beken S, Dursun A, Dilli D, Okumus N. Association of vitamin D deficiency with acute lower respiratory tract infections in newborns. J Matern Fetal Neonatal Med. 2015, Epub March 19.
    1. Karatekin G, Kaya A, Salihoğlu O, Balci H, Nuhoğlu A. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur J Clin Nutr. 2009;63:473–437. doi: 10.1038/sj.ejcn.1602960.
    1. Bosis S, Esposito S, Niesters HG, Crovari P, Osterhaus AD, Principi N. Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses. J Med Virol. 2005;75:101–4. doi: 10.1002/jmv.20243.
    1. Hansdottir S, Monick MM, Lovan N, Powers L, Gerke A, Hunninghake GW. Vitamin D decreases respiratory syncytial virus induction of NF-kappaB-linked chemokines and cytokines in airway epithelium while maintaining the antiviral state. J Immunol. 2010;184:965–74. doi: 10.4049/jimmunol.0902840.
    1. Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S. Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. J Infect Dis. 2008;197:676–80. doi: 10.1086/527488.
    1. McNally JD, Sampson M, Matheson LA, Hutton B, Little J. Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic review and meta-analysis. Pediatr Pulmonol. 2014;49:790–9. doi: 10.1002/ppul.22877.
    1. McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K, Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol. 2009;44:981–8. doi: 10.1002/ppul.21089.
    1. Roth DE, Shah R, Black RE, Baqui AH. Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh. Acta Paediatr. 2010;99:389–93. doi: 10.1111/j.1651-2227.2009.01594.x.
    1. Randolph AG, Yip WK, Falkenstein-Hagander K, Weiss ST, Janssen R, Keisling S, et al. Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis. Clin Exp Allergy. 2014;44:231–7. doi: 10.1111/cea.12247.
    1. Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S. Vitamin D status is not associated with the risk of hospitalization for acute bronchioitis in early childhood. Eur J Clin Nutr. 2009;6:297–9. doi: 10.1038/sj.ejcn.1602946.
    1. Belderbos ME, Houben ML, Wilbrink B, Lentjes E, Bloemen EM, Kimpen JL, et al. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011;127:e1513–20. doi: 10.1542/peds.2010-3054.
    1. Camargo CA, Jr, Ingham T, Wickens K, Thadhani R, Silvers KM, Epton MJ, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011;127:e180–7. doi: 10.1542/peds.2010-0442.
    1. Esposito S, Principi N. Unsolved problems in the approach to pediatric community-acquired pneumonia. Curr Opin Infect Dis. 2012;25:286–91. doi: 10.1097/QCO.0b013e328352b60c.
    1. Muhe L, Lulseged S, Mason KE, Simoes EA. Case–control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet. 1997;349:1801–4. doi: 10.1016/S0140-6736(96)12098-5.
    1. Oduwole AO, Renner JK, Disu E, Ibitoye E, Emokpae E. Relationship between vitamin D levels and outcome of pneumonia in children. West Afr J Med. 2010;29:373–8.
    1. Haider N, Nagi AG, Khan KM. Frequency of nutritional rickets in children admitted with severe pneumonia. J Pak Med Assoc. 2010;60:729–32.
    1. Ren J, Sun B, Miao P, Feng X. Correlation between serum vitamin D level and severity of community acquired pneumonia in young children. Zhongguo Dang Dai Er Ke Za Zhi. 2013;15:519–21.
    1. Zhou W, Zuo X, Li J, Yu Z. Effects of nutrition intervention on the nutritional status and outcomes of paediatric patients with pneumonia. Minerva Pediatr. 2015, Epub Mar 31.
    1. Li W, Guo L, Li H, Sun C, Cui X, Song G, et al. Polymorphism rs2239185 in vitamin D receptor gene is associated with severe community-acquired pneumonia of children in Chinese Han population: a case–control study. Eur J Pediatr. 2015;174:621–9. doi: 10.1007/s00431-014-2433-0.
    1. 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. doi: 10.1111/j.1365-3156.2010.02578.x.
    1. 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. doi: 10.1016/S0140-6736(11)61650-4.
    1. Choudhary N, Gupta P. Vitamin D supplementation for severe pneumonia: a randomized controlled trial. Indian Pediatr. 2011;49:449–54. doi: 10.1007/s13312-012-0073-x.
    1. Das RR, Singh M, Panigrahi I, Naik SS. Vitamin d supplementation for the treatment of acute childhood pneumonia: a systematic review. ISRN Pediatr. 2013;19:459–60.
    1. Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 2007;158:1–235.
    1. Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Committee to review dietary reference intakes for vitamin D and calcium. Institute of Medicine: Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academic Press; 2001.
    1. 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. doi: 10.3945/ajcn.2009.29094.
    1. Inamo Y, Hasegawa M, Saito K, Hayashi R, Ishikawa T, Yoshino Y, et al. Serum vitamin D concentrations and associated severity of acute lower respiratory tract infections in Japanese hospitalized children. Pediatr Int. 2011;53:199–201. doi: 10.1111/j.1442-200X.2010.03224.x.
    1. Holick MF, Binkley NC, Bishoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30. doi: 10.1210/jc.2011-0385.

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