{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:21:04Z","timestamp":1789730464310,"version":"4.0.1"},"reference-count":112,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T00:00:00Z","timestamp":1374796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing. This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms?  In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease.<\/jats:p>","DOI":"10.3390\/nu5082880","type":"journal-article","created":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T22:13:15Z","timestamp":1374876795000},"page":"2880-2900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Vitamin D Deficiency and the Lung: Disease Initiator  or Disease Modifier?"],"prefix":"10.3390","volume":"5","author":[{"given":"Rachel","family":"Foong","sequence":"first","affiliation":[{"name":"Centre for Child Health Research, Telethon Institute for Child Health Research, The University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Zosky","sequence":"additional","affiliation":[{"name":"Centre for Child Health Research, Telethon Institute for Child Health Research, The University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1678S","DOI":"10.1093\/ajcn\/80.6.1678S","article-title":"Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers and cardiovascular disease","volume":"80","author":"Holick","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_3","unstructured":"(2011). Dietary Reference Intakes for Calcium and Vitamin D, The National Academic Press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"582S","DOI":"10.1093\/ajcn\/88.2.582S","article-title":"Pharmacokinetics of vitamin D toxicity","volume":"88","author":"Jones","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1136\/thx.2009.128793","article-title":"The vitamin D axis in the lung: A key role for vitamin D-binding protein","volume":"65","author":"Chishimba","year":"2010","journal-title":"Thorax"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nri3045","article-title":"Modulation of the immune system by UV radiation: More than just the effects of vitamin D?","volume":"11","author":"Hart","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/aje\/kwn163","article-title":"Frequency of leisure-time physical activity and serum 25-hydroxyvitamin D levels in the US population: Results from the third national health and nutrition examination survey","volume":"168","author":"Scragg","year":"2008","journal-title":"Am. J. Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/02770900701554896","article-title":"The association between smoking, physical inactivity, obesity and asthma severity in the general US population","volume":"44","author":"Strine","year":"2007","journal-title":"J. Asthma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1378\/chest.113.4.900","article-title":"Impaired skeletal muscle endurance related to physical inactivity and altered lung function in COPD patients","volume":"113","author":"Serres","year":"1998","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3945\/an.111.000398","article-title":"Vitamin D and chronic lung disease: A review of molecular mechanisms and clinical studies","volume":"2","author":"Finklea","year":"2011","journal-title":"Adv.Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/mnfr.201000174","article-title":"A review of critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency","volume":"55","author":"Schwalfenberg","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.1128\/IAI.00353-08","article-title":"Vitamin D signalling, infectious diseases and regulation of innate immunity","volume":"76","author":"White","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/ncpendmet0716","article-title":"Unexpected actions of vitamin D: New perspectives on the regulation of innate and adaptive immunity","volume":"4","author":"Adams","year":"2008","journal-title":"Nat. Clin. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.4049\/jimmunol.173.5.2909","article-title":"Cutting Edge: 1,25-Dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression","volume":"173","author":"Wang","year":"2004","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1080\/01902140701756687","article-title":"The role of epithelial \u03b2-defensins and cathelicidins in host defense of the lung","volume":"33","author":"Hiemstra","year":"2007","journal-title":"Exp. Lung Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1126\/science.1123933","article-title":"Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response","volume":"311","author":"Liu","year":"2006","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/0092-8674(89)90688-0","article-title":"The major human rhinovirus receptor is ICAM-1","volume":"56","author":"Greve","year":"1989","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.cellbi.2006.01.004","article-title":"1,25-Dihydroxyvitamin D3 inhibits tumor necrosis factor-\u03b1-induced adhesion molecule expression in endothelial cells","volume":"30","author":"Martinesi","year":"2006","journal-title":"Cell Biol. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/ibd.20354","article-title":"Vitamin D derivatives induce apoptosis and downregulate ICAM-1 levels in peripheral blood mononuclear cells of inflammatory bowel disease patients","volume":"14","author":"Martinesi","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1017\/S0950268806007175","article-title":"Epidemic influenza and vitamin D","volume":"134","author":"Cannell","year":"2006","journal-title":"Epidemiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jolliffe, D.A., Griffiths, C.J., and Martineau, A.R. (2012). Vitamin D in the prevention of acute respiratory infection: Systematic review of clinical studies. J. Steroid Biochem. Mol. Biol.","DOI":"10.1136\/thoraxjnl-2012-202678.160"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1056\/NEJMra0804579","article-title":"Asthma","volume":"360","author":"Fanta","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/ni.1892","article-title":"The many paths to asthma: Phenotype shaped by innate and adaptive immunity","volume":"11","author":"Kim","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1183\/09031936.00181608","article-title":"Airway smooth muscle thickness in asthma is related to severity but not duration of asthma","volume":"34","author":"James","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jaci.2007.08.028","article-title":"Is vitamin D deficiency to blame for the asthma epidemic?","volume":"120","author":"Litonjua","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e18492","DOI":"10.1371\/journal.pone.0018492","article-title":"Asthma prevalence associated with geographical latitude and regional isolation in the United States of America and Australia","volume":"6","author":"Krstic","year":"2011","journal-title":"PLoS One"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1183\/09031936.00029011","article-title":"Vitamin D and atopy and asthma phenotypes in children: A longitudinal cohort study","volume":"38","author":"Hollams","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jpeds.2010.08.043","article-title":"Vitamin D serum levels and markers of asthma control in Italian children","volume":"158","author":"Chinellato","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.jaci.2010.03.008","article-title":"Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use","volume":"125","author":"Searing","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1164\/rccm.200911-1710OC","article-title":"Vitamin D levels, lung function, and steroid response in adult asthma","volume":"181","author":"Sutherland","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/ajcn\/85.3.788","article-title":"Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age","volume":"85","author":"Camargo","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/ajcn\/85.3.853","article-title":"Maternal vitamin D intake during pregnancy and early childhood wheezing","volume":"85","author":"Devereux","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/j.1365-2222.2009.03234.x","article-title":"Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children","volume":"39","author":"Erkkola","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1196\/annals.1337.013","article-title":"Infant vitamin D supplementation and allergic conditions in adulthood: Northern Finland birth cohort 1966","volume":"1037","author":"Sovio","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/sj.ejcn.1602680","article-title":"Maternal vitamin D status during pregnancy and child outcomes","volume":"62","author":"Gale","year":"2008","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1136\/thoraxjnl-2012-201888","article-title":"Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes","volume":"67","author":"Pike","year":"2012","journal-title":"Thorax"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/EDE.0b013e31823a44d3","article-title":"Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring","volume":"23","author":"Morales","year":"2012","journal-title":"Epidemiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1542\/peds.2010-0442","article-title":"Cord-blood 25-hydroxyvitamin D Levels and risk of respiratory infection, wheezing, and asthma","volume":"127","author":"Camargo","year":"2011","journal-title":"Pediatrics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.jaci.2010.01.024","article-title":"Do early-life viral infections cause asthma?","volume":"125","author":"Sly","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1164\/rccm.201107-1239OC","article-title":"Relationship between serum vitamin D, disease severity and airway remodeling in children with asthma","volume":"184","author":"Gupta","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1440-1843.2007.01099.x","article-title":"Effect of 1,25-(OH)2D3 (a vitamin D analogue) on passively sensitized human airway smooth muscle cells","volume":"12","author":"Song","year":"2007","journal-title":"Respirology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/j.1476-5381.2009.00428.x","article-title":"Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1","volume":"158","author":"Damera","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jsbmb.2004.03.054","article-title":"1,25-Dihydroxyvitamin D3 and fetal lung maturation: Immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 biphosphatase","volume":"89","author":"Nguyen","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L392","DOI":"10.1152\/ajplung.1996.271.3.L392","article-title":"Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium","volume":"271","author":"Nguyen","year":"1996","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1164\/rccm.201010-1596OC","article-title":"Vitamin D deficiency causes deficits in lung function and alters lung structure","volume":"183","author":"Zosky","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/j.1365-2222.2008.02971.x","article-title":"Pathogenesis of Asthma","volume":"38","author":"Holgate","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4974","DOI":"10.4049\/jimmunol.167.9.4974","article-title":"1\u03b1,25-dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th-2 cells","volume":"167","author":"Boonstra","year":"2001","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.1073\/pnas.84.10.3385","article-title":"1\u03b1,25-dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes","volume":"84","author":"Reichel","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","first-page":"12","article-title":"1\u03b1,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells","volume":"52","author":"Pichler","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/eji.200324532","article-title":"The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing","volume":"34","author":"Topilski","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0091-6749(03)01855-4","article-title":"Dual effects of vitamin D-induced alteration of TH1\/TH2 cytokine expression: Enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease","volume":"112","author":"Matheu","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e67823","DOI":"10.1371\/journal.pone.0067823","article-title":"Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease","volume":"8","author":"Gorman","year":"2013","journal-title":"PLoS One"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1136\/thx.2005.045187","article-title":"Asthma exacerbations 3: Pathogenesis","volume":"61","author":"Wark","year":"2006","journal-title":"Thorax"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1164\/rccm.200808-1361OC","article-title":"Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica","volume":"179","author":"Brehm","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jaci.2010.03.043","article-title":"Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study","volume":"126","author":"Brehm","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1164\/rccm.201203-0431OC","article-title":"Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children","volume":"186","author":"Brehm","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/S0140-6736(09)60326-3","article-title":"Glucocorticoid resistance in inflammatory diseases","volume":"373","author":"Barnes","year":"2009","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1172\/JCI21759","article-title":"Reversing the defective induction of IL-10 secreting regulatory T cells in glucocorticoid-resistant asthma patients","volume":"116","author":"Xystrakis","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1152\/physiolgenomics.00134.2006","article-title":"1\u03b1,25-Dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes","volume":"29","author":"Bosse","year":"2007","journal-title":"Physiol. Genomics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1136\/bmj.310.6989.1225","article-title":"Community study of role of viral infections in exacerbations of asthma in 9\u201311 year old children","volume":"310","author":"Johnston","year":"1995","journal-title":"Br. Med. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(11)60968-9","article-title":"Chronic obstructive pulmonary disease","volume":"379","author":"Decramer","year":"2012","journal-title":"Lancet"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1164\/rccm.200703-456SO","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease","volume":"176","author":"Rabe","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/thx.2008.112136","article-title":"Early life origins of chronic obstructive pulmonary disease","volume":"65","author":"Svanes","year":"2010","journal-title":"Thorax"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1177\/1753465813479428","article-title":"Early life influences on the development of chronic obstructive pulmonary disease","volume":"7","author":"Stocks","year":"2013","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1183\/09031936.50130408","article-title":"Current status of research on osteoporosis in COPD: A systematic review","volume":"34","author":"Wouters","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1689S","DOI":"10.1093\/ajcn\/80.6.1689S","article-title":"Overview of general physiologic features and functions of vitamin D","volume":"80","author":"DeLuca","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1136\/thx.2009.120659","article-title":"Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene","volume":"65","author":"Janssens","year":"2010","journal-title":"Thorax"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2796.2004.01337.x","article-title":"Vitamin D deficiency, bone mineral density and weight in patients with advanced pulmonary disease","volume":"256","author":"Halse","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1378\/chest.128.6.3792","article-title":"Relationship between serum 25-hydroxyvitamin D and pulmonary function in the third national health and nutrition examination survey","volume":"128","author":"Black","year":"2005","journal-title":"Chest"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/thx.2010.155234","article-title":"Relationship of vitamin D status to adult lung function and COPD","volume":"66","author":"Shaheen","year":"2011","journal-title":"Thorax"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/ppul.1950080308","article-title":"Tracking lung function in healthy children and adolescents","volume":"8","author":"Hibbert","year":"1990","journal-title":"Pediatr. Pulmonol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1136\/thx.2008.103978","article-title":"Association between birth weight, early childhood weight gain and adult lung function","volume":"64","author":"Hancox","year":"2009","journal-title":"Thorax"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"258","DOI":"10.4046\/trd.2012.73.5.258","article-title":"Inhibition of vitamin D receptor translocation by cigarette smoking extracts","volume":"73","author":"Uh","year":"2012","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1164\/rccm.201007-1125OC","article-title":"Risk factors for chronic obstructive pulmonary disease in a European cohort of young adults","volume":"183","author":"Accordini","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1164\/ajrccm.157.3.9709027","article-title":"CD8+ T-Lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease","volume":"157","author":"Saetta","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1136\/thx.2010.140921","article-title":"Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages","volume":"66","author":"Wood","year":"2011","journal-title":"Thorax"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.rmed.2004.10.022","article-title":"Sputum matrix metalloproteases: Comparison between chronic obstructive pulmonary disease and asthma","volume":"99","author":"Culpitt","year":"2005","journal-title":"Respir. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbrc.2011.02.011","article-title":"Deletion of vitamin D receptor leads to premature emphysema\/COPD by increased matrix metalloproteinases and lymphoid aggregates formation","volume":"406","author":"Sundar","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"46S","DOI":"10.1183\/09031936.03.00078002","article-title":"COPD exacerbations: definitions and classifications","volume":"41","author":"Burge","year":"2003","journal-title":"Eur. Respir. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1183\/09031936.00109906","article-title":"Exacerbations of chronic obstructive pulmonary disease","volume":"29","author":"Celli","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1164\/rccm.200506-859OC","article-title":"Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations","volume":"173","author":"Papi","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1378\/chest.129.2.317","article-title":"Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of copd","volume":"129","author":"Wilkinson","year":"2006","journal-title":"Chest"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1164\/rccm.201006-0833OC","article-title":"Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation","volume":"183","author":"Mallia","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1471-2466-12-28","article-title":"25-hydroxyvitamin D deficiency, exacerbation frequency and human rhinovirus exacerbations in chronic obstructive pulmonary disease","volume":"12","author":"Quint","year":"2012","journal-title":"BMC Pulm. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1164\/rccm.201109-1644OC","article-title":"Vitamin D levels and risk of acute exacerbations of chronic obstructive pulmonary disease: A prospective cohort study","volume":"185","author":"Kunisaki","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e38934","DOI":"10.1371\/journal.pone.0038934","article-title":"Chronic obstructive pulmonary disease is associated with low levels of vitamin D","volume":"7","author":"Persson","year":"2012","journal-title":"PLoS One"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"105","DOI":"10.7326\/0003-4819-156-2-201201170-00004","article-title":"High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: A randomized trial","volume":"156","author":"Lehouck","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/toxsci\/64.1.4","article-title":"A short history of lung cancer","volume":"64","author":"Witschi","year":"2001","journal-title":"Toxicol. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1056\/NEJMra0802714","article-title":"Lung cancer","volume":"359","author":"Herbst","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1002\/ijc.25516","article-title":"Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008","volume":"127","author":"Ferlay","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1093\/carcin\/16.9.2091","article-title":"Inhibition of intestinal tumor development in rat multi-organ carcinogenesis and abberant crypt foci in rat colon carcinogenesis by 22-oxa-calcitriol, a synthetic analogue of 1\u03b1,25-dihydroxyvitamin D3","volume":"16","author":"Otoshi","year":"1995","journal-title":"Carcinogenesis"},{"key":"ref_92","first-page":"2644","article-title":"1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and down-modulates p21Waf1\/Cip1 in vitro and in vivo","volume":"59","author":"Hershberger","year":"1999","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1093\/carcin\/bgi049","article-title":"22-Oxa-1\u03b1,25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer","volume":"26","author":"Nakagawa","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.mce.2012.02.006","article-title":"CYP24 inhibition preserves 1\u03b1,25-dihydroxyvitamin D(3) anti-proliferative signaling in lung cancer cells","volume":"355","author":"Zhang","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1002\/ijc.22462","article-title":"Inhibition of lung carcinogenesis by 1\u03b1,25-dihydroxyvitamin D3 and 9-cis retinoic acid in the A\/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity","volume":"120","author":"Mernitz","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jsbmb.2004.03.066","article-title":"Metastatic growth of lung cancer cells is extremely reduced in Vitamin D receptor knockout mice","volume":"89\u201390","author":"Nakagawa","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1158\/1055-9965.EPI-08-0199","article-title":"Vitamin D Status and the risk of lung cancer: A cohort study in Finland","volume":"17","author":"Kilkkinen","year":"2008","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e20796","DOI":"10.1371\/journal.pone.0020796","article-title":"Serum 25-hydroxyvitamin D and risk of lung cancer in male smokers: A nested case-control study","volume":"6","author":"Weinstein","year":"2011","journal-title":"PLoS One"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1093\/jn\/135.10.2350","article-title":"Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb\/c mice","volume":"135","author":"Tangpricha","year":"2005","journal-title":"J. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ijc.25992","article-title":"Inactivation of the vitamin D receptor in APCmin\/+ mice reveals a critical role for the vitamin D receptor in intestinal tumor growth","volume":"130","author":"Zheng","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jsbmb.2005.06.024","article-title":"Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues","volume":"97","author":"Zinser","year":"2005","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1042\/BJ20110744","article-title":"Vitamin D and cancer: A review of molecular mechanisms","volume":"441","author":"Fleet","year":"2012","journal-title":"Biochem. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/ijc.22058","article-title":"CYP24, the enzyme that catabolizes the antiproliferative agent vitamin D, is increased in lung cance","volume":"119","author":"Parise","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1158\/1078-0432.CCR-10-1789","article-title":"CYP24A1 is an independent prognostic marker of survival in patients with lung adenocarcinoma","volume":"17","author":"Chen","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7090","DOI":"10.4049\/jimmunol.181.10.7090","article-title":"Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense","volume":"181","author":"Hansdottir","year":"2008","journal-title":"J. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1007\/s10552-012-0033-8","article-title":"Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: A potential nutrient-nutrient interaction","volume":"23","author":"Cheng","year":"2012","journal-title":"Cancer Causes Control"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1158\/1055-9965.EPI-05-0335","article-title":"Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients","volume":"14","author":"Zhou","year":"2005","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1200\/JCO.2006.07.5358","article-title":"Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients","volume":"25","author":"Zhou","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/icvts\/ivr063","article-title":"The effect of season of operation on the survival of patients with resected non-small cell lung cancer","volume":"14","author":"Turna","year":"2012","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.1200\/JCO.2008.18.0406","article-title":"Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer","volume":"26","author":"Heist","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jsbmb.2010.10.002","article-title":"Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer","volume":"123","author":"Srinivasan","year":"2011","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1183\/09031936.00002912","article-title":"Circulating DBP level and prognosis in operated lung cancer: An exploration of pathophysiology","volume":"41","author":"Turner","year":"2013","journal-title":"Eur. Respir. J."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/5\/8\/2880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:15Z","timestamp":1760219295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/5\/8\/2880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,26]]},"references-count":112,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8]]}},"alternative-id":["nu5082880"],"URL":"https:\/\/doi.org\/10.3390\/nu5082880","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,26]]}}}