Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiolgy (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function

Authors: XU, JIAYI - Cornell University; BARTZ, TRACI - University Of Washington; CHITTOOR, GEETHA - University Of North Carolina; EIRIKSDOTTIR, GUDNY - Icelandic Heart Association; MANICHAIKUL, ANI - University Of Virginia School Of Medicine; SUN, FANGUI - Boston University School Of Public Health; TERZIKHAN, NATALIE - Erasmus Medical Center; ZHOU, XIA - University Of Minnesota; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BRUSSELLE, GUY - Erasmus Medical Center; DE BOER, IAN - University Of Washington; FORNAGE, MYRIAM - University Of Texas Health Science Center; FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); GRAFF, MARIAELISA - University Of North Carolina; GUDNASON, VILMUNDUR - Icelandic Heart Association; HARRIS, TAMARA - National Institute On Aging (NIA, NIH); HOFMAN, ALBERT - Erasmus Medical Center; HOU, RUIXUE - University Of North Carolina; HOUSTON, DENISE - Wake Forest School Of Medicine; JACOBS JR, DAVID - University Of Minnesota; KRITCHEVSKY, STEPHEN - Wake Forest School Of Medicine; LATOURELLE, JEANN - Boston University; LEMAITRE, ROZENN - University Of Washington; LUTSEY, PAMELA - University Of Minnesota; O'CONNOR, GEORGE - Boston University; OELSNER, ELIZABETH - Columbia University - New York; PANKOW, JAMES - University Of Minnesota; PSATY, BRUCE - University Of Washington; ROHDE, REBECCA - University Of North Carolina; RICH, STEPHEN - University Of Virginia School Of Medicine; ROTTER, JEROME - Harbor-Ucla Medical Center; SMITH, LEWIS - Northwestern University; STRICKER, BRUNO - Erasmus Medical Center; VORUGANTI, V - University Of North Carolina; WANG, THOMAS - Vanderbilt University; ZILLIKENS, M - Erasmus Medical Center; BARR, R - Columbia University - New York; DUPUIS, JOSEE - Boston University School Of Public Health; GHARIB, SINA - University Of Washington; LAHOUSSE, LIES - Erasmus Medical Center; LONDON, STEPHANIE - National Institute Of Environmental Health Sciences (NIEHS, NIH); NORTH, KARI - University Of North Carolina; SMITH, ALBERT - Icelandic Heart Association; STEFFEN, LYN - University Of Minnesota; HANCOCK, DANA - Rti International, Usa; CASSANO, PATRICIA - Cornell University

Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/9/2018
Publication Date: 9/12/2018
Citation: Xu, J., Bartz, T.M., Chittoor, G., Eiriksdottir, G., Manichaikul, A.W., Sun, F., Terzikhan, N., Zhou, X., Booth, S.L., Brusselle, G.G., De Boer, I.H., Fornage, M., Frazier-Wood, A.C., Graff, M., Gudnason, V., Harris, T.B., Hofman, A., Hou, R., Houston, D.K., Jacobs Jr, D.R., Kritchevsky, S.B., Latourelle, J., Lemaitre, R.N., Lutsey, P.L., O'Connor, G., Oelsner, E.C., Pankow, J.S., Psaty, B.M., Rohde, R.R., Rich, S.S., Rotter, J.I., Smith, L.J., Stricker, B.H., Voruganti, V.S., Wang, T.J., Zillikens, M.C., Barr, R.G., Dupuis, J., Gharib, S.A., Lahousse, L., London, S.J., North, K.E., Smith, A.V., Steffen, L.M., Hancock, D.B., Cassano, P.A. 2018. Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiolgy (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function. British Journal of Nutrition. https://doi.org/10.1017/S0007114518002180.
DOI: https://doi.org/10.1017/S0007114518002180

Interpretive Summary: Obesity is a risk factor for chronic obstructive pulmonary disease (COPD), and weight loss can reduce COPD. COPD is the third leading cause of mortality in the U.S. and among the top ten leading causes of total years of life lost in the world. COPD causes airflow from the lungs to be restricted. Scientists think that vitamin D may protect against COPD through the regulation of genes, and individuals with obesity have lower levels of Vitamin D in their blood on average. In order to study the effect of vitamin D on pulmonary (lung) function in humans, scientists have studied vitamin D metabolites. Metabolites are intermediate products between Vitamin D as it is ingested or produced by the body, and it’s absorption into the body where it can be used. One such metabolite that has been found to assist in pulmonary function is 1,25-dihydroxyvitamin D (1,25-(OH)2D), which is the active vitamin D metabolite. The common biomarker (biological markers or things found in the body) of vitamin D is Total 25(OH)D. On average, African ancestry (AA) populations have lower serum (in blood) 25(OH)D concentrations, but higher 1,25-(OH)2D levels and greater bone mineral density compared to European ancestry (EA) populations. Mixed results have been reported in previous studies of the vitamin D-pulmonary function association in the general population. Additionally, only one study has examined vitamin D and pulmonary function in ancestry groups other than European. To address these mixed findings and expand the literature to other ancestry groups, we analyzed data collected as part of the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium). We studied the relationship of serum 25(OH) and pulmonary function in 22,838 EA and 4,290 AA participants. We also examined the effect of cigarette smoking. We consistently found positive relationship of serum 25(OH)D with pulmonary function across both EA and AA groups. In addition, in the EA group, a significantly stronger relationship was found for current and former smokers, compared to never smokers. This finding highlights the importance of vitamin D in vulnerable populations. Because of the observational design of this study, we cannot conclude a causal relationship. Future studies, are needed to further examine the causality of 25(OH)D on pulmonary function.

Technical Abstract: The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1.1 ml in EA (95 % CI 0.9, 1.3; P<0·0001) and 1.8 ml (95 % CI 1.1, 2.5; P<0.0001) in AA (P race difference=0.06), and forced vital capacity (FVC) was higher by 1.3 ml in EA (95 % CI 1.0, 1.6; P<0.0001) and 1.5 ml (95 % CI 0.8, 2.3; P=0.0001) in AA (P race difference=0.56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1.7 ml (95 % CI 1.1, 2.3) for current smokers and 1.7 ml (95 % CI 1.2, 2.1) for former smokers, compared with 0.8 ml (95 % CI 0.4, 1.2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.