Large Meta-Analysis in the CHARGE Consortium Provides Evidence For an Association of Serum Vitamin D With Pulmonary Function
Authors: Xu Jiayi , Bartz Traci M. , Chittoor Geetha , Eiriksdottir Gudny , Manichaikul Ani W. , Sun Fangui , Terzikhan Natalie , Zhou Xia , Booth Sarah L. , Brusselle Guy G. , de Boer Ian H. , Fornage Myriam , Frazier-Wood Alexis C. , Graff Mariaelisa , Gudnason Vilmundur , Harris Tamara B. , Hofman Albert , Hou Ruixue , Houston Denise K. , Jacobs David R. , Kritchevsky Stephen B. , Latourelle Jeanne , Lemaitre Rozenn N. , Lutsey Pamela L. , O’Connor George , Oelsner Elizabeth C. , Pankow James S. , Psaty Bruce M. , Rohde Rebecca R. , Rich Stephen S. , Rotter Jerome I. , Smith Lewis J. , Stricker Bruno H. , Voruganti V. Saroja , Wang Thomas J. , Zillikens M. Carola , Barr R. Graham , Dupuis Josée , Gharib Sina A. , Lahousse Lies , London Stephanie J. , North Kari E. , Smith Albert V. , Steffen Lyn M. , Hancock Dana B. , Cassano Patricia A. 
Published: June 2017

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for the association of serum 25-hydroxyvitamin D [25(OH)D] and pulmonary function. 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=4,290) in the CHARGE Consortium. Data were analyzed 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 (SD) serum 25(OH)D was 68 (29) nmol/L for EAs and 49 (21) nmol/L for AAs. For each 1 nmol/L higher 25(OH)D, forced expiratory volume in the first second (FEV1) was higher by 1.1 mL in EAs (95% CI: 0.9,1.3; P=2.5×10-21) and 1.8 mL (95% CI: 1.1,2.5; P=1.6×10-7) in Aas (Prace difference=0.06), and forced vital capacity (FVC) was higher by 1.3 mL in EAs (95% CI: 1.0,1.6; P=1.1×10-20) and 1.5 mL (95% CI: 0.8,2.3; P=1.2×10-4) in AAs (Prace difference=0.56). Among EAs, the 25(OH)D–FVC association was stronger in smokers: per 1nmol/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 to 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 EAs, a stronger association was observed for smokers compared to never smokers, which supports the importance of vitamin D in vulnerable populations.

Cohort Funding

This work was supported by National Institutes of Health (NIH) grant number R21 HL125574 funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Office of Dietary Supplements (ODS) (co-Principal Investigators [co-PIs]: DBH and PAC). The corresponding author (PAC) had full access to the data for the meta-analysis, and had final responsibility for the decision to submit for publication. No funding source had any role in the analysis of the data, the writing of the manuscript, or the decision to submit it. This work was also supported in part by R01HL077612 (PI: RGB) and by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (ZO1 ES043012, PI: SJL). SJL is supported by the Intramural Research Program of NIH, National Institute of Environmental Health Sciences. Infrastructure for the CHARGE Consortium is supported in part by the NHLBI grant R01HL105756.

The Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study has been funded by NIH contracts N01-AG-1-2100 and 271201200022C, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study.

The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NHLBI contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. 25(OH)D measurements were conducted with the support of R01 HL103706 from the NHLBI and R01 HL103706-S1 from the NIH ODS. The authors thank the staff and participants of the ARIC study for their important contributions.

This Cardiovascular Health Study (CHS) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL085251, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Vitamin D measurements were made possible by NHLBI (R01HL084443-01A2).

This work in Framingham Heart Study was supported by NHLBI’s Framingham Heart Study contract (N01-HC-25195 and HHSN268201500001I). Vitamin D measurements in the Framingham study were made possible by NIA (R01 AG14759 to SLB.).

The Health Aging and Body Composition cohort study was supported by NIA contracts N01AG62101, N01AG2103, and N01AG62106, NIA grant R01-AG028050, NINR grant R01-NR012459, and in part by the Intramural Research Program of the NIA, NIH. This research was further supported by RC1AG035835, and the serum vitamin D assays were supported by R01AG029364.

The Multi-Ethnic Study of Atherosclerosis (MESA) study is conducted and supported by NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from NHLBI, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001881 from NCRR, and DK063491 from the NIDDK. The MESA Lung study was supported by grants R01 HL077612, RC1 HL100543 and R01 HL093081 from NHLBI. Support for the Mineral Metabolite dataset was provided by grant HL096875.

The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands; the Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Dutch Ministry of Education, Culture, and Science; the Dutch Ministry for Health, Welfare, and Sports; the European Commission (DG XII), and the Municipality of Rotterdam. LL was a postdoctoral fellow of the Research Foundation—Flanders (FWO) in Brussels, Belgium. Part of this work was supported by a FWO-grant G035014N. DSM Nutritional Products AG, Kaiseraugst, Switzerland, sponsored the Vitamin D serum analyses. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists.

The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005).

Author Disclosure

Dr. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson.

All other authors have no conflicts of interest. There is no commercial support or financial interest from the tobacco industry for the research presented.

The study sponsors were not involved in study design, data collection, data analysis, data interpretation, report writing, or decisions to submit the paper for publication. PAC and DBH had final responsibility for the decision to submit for publication.

Online Supporting Material

Supplemental table, figures, and methods are available.

Abbreviation Footnote

25(OH)D

25-Hydroxyvitamin D

AA

African Ancestry

AGES

Age, Gene, Environment, Susceptibility Study—Reykjavik, Iceland

ARIC

Atherosclerosis Risk in Communities Study

CARDIA

Coronary Artery Risk Development in Young Adults Study

CHARGE

Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

CHS

Cardiovascular Health Study

CLIA

Chemiluminescence Immunoassay

COPD

Chronic Obstructive Pulmonary Disease

EA

European Ancestry

FEV1

Forced Expiratory Volume in the First Second

FHS (Offspring)

Framingham Heart Study—Offspring Cohort

FHS (Gen3)

Framingham Heart Study—Generation 3 Cohort

FVC

Forced Vital Capacity

HABC

Health, Aging, and Body Composition Study

LC-MS/MS

Liquid Chromatography in Tandem with Mass Spectrometry

MESA

Multi-Ethnic Study of Atherosclerosis

NHANES

National Health and Nutrition Examination Survey

PFT

Pulmonary Function Test

RIA

Radioimmunoassay

RS

Rotterdam (Netherlands) Study