Vitamin D deficiency is associated with the severity of COPD: a systematic review and meta-analysis

Figures & data

Figure 1 A flowchart of identified studies.

Abbreviation: 25(OH)D, 25-hydroxyvitamin D.

Table 1 Included studies for the serum levels of 25(OH)D

Authors	Publication year	Country/city	Design	Controls	Match	Number (controls/COPD)	Serum levels of 25(OH)D		NOS scores	References
							Controls (M ± SD)	COPD (M ± SD)
Yang et al	2015	People’s Republic of China	Case-control	Healthy	Age, sex, and smoking habits	51/84	18.1±9.4 ng/mL	13.1±6.9 ng/mLa 9.3±5.8 ng/mLb	7	^Citation31
Yang et al	2015	People’s Republic of China	Case-control	Healthy	Age, sex, and smoking habits	36/36	52.3±15.43 nmol/L	33.63±10.3 nmol/Lc	6	^Citation32
Mahlin et al	2014	Sweden	Case-control	Healthy	Sex	149/98	57.6±23.1 nmol/L	51.5±22.0 nmol/L	8	^Citation29
Zhou et al	2012	People’s Republic of China	Case-control	With normal lung function	Sex, age	181/193	35.8±12.4 nmol/L	32.1±10.8 nmol/L	6	^Citation30
Duckers et al	2011	UK	Case-control	Healthy	Age and sex	30/30	16.1±1.4 μg/L	11.4±1.9 μg/L	6	^Citation33
Xiaomei et al	2014	People’s Republic of China	Cohort	Without COPD	Age and sex	50/50	13.0±5.7 ng/mL	13.6±5.7 ng/mL	7	^Citation19
Persson et al	2012	Bergen	Cohort	Without COPD	Sex	134/133	25.0±9.5 ng/mL	25.2±10.0 ng/mL	7	^Citation34
Jackson et al	2013	UK	Cohort	NA	Age and sex	100/104	55.4±28.3 nmol/L	48.5±25.5 nmol/L	6	^Citation18
Janssens et al	2010	Belgium	Cohort	Healthy smokers	Sex	152/262	24.6±8.7 ng/mL	19.9±8.2 ng/mL	7	^Citation20

Notes:

a Low risk with FEV₁ %pred ≥50% and less than two treated exacerbation per year.

b High risk with FEV₁ %pred <50%, or two or more treated exacerbations per year, or one or more hospitalizations for COPD exacerbations per year.

c Acute exacerbation COPD.

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; FEV₁%pred, forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) predicted; M, mean; NA, not applicable; NOS, Newcastle–Ottawa Scale; SD, standard deviation.

Table 2 Included studies for deficiency rate of 25(OH)D

Authors	Publication year	Country/city	Design	Controls	Match	Number				NOS scores	References
						Controls/COPD	Mild	Moderate	Severe
Lee et al	2014	USA	Cohort	No COPD	None	5877/1869	932	NA	937	8	^Citation21
Xiaomei et al	2014	People’s Republic of China	Cohort	Without COPD	Age and sex	50/50	NA	NA	NA	7	^Citation19
Persson et al	2012	Bergen	Cohort	Without COPD	Sex	134/133	NA	NA	NA	7	^Citation34
Janssens et al	2010	Belgium	Cohort	Healthy smokers	Sex	152/262	70	87	192	7	^Citation20
Zhou et al	2012	People’s Republic of China	Case-control	Healthy	Age and sex	181/193	NA	NA	NA	6	^Citation30
Duckers et al	2011	UK	Case-control	Healthy	Age and sex	30/30	NA	NA	NA	6	^Citation33
Jung et al	2015	Korea	Cohort	NA	NA	NA	24	105	169	5	^Citation35
Persson et al	2015	Bergen	Cohort	NA	NA	NA	NA	201	216	7	^Citation36
Romme et al	2013	Netherlands	Cohort	NA	NA	NA	NA	42	109	6	^Citation37

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; NA, not applicable; NOS, Newcastle–Ottawa Scale.

Table 3 Included studies for curative effect and safety of vitamin D intake

Authors	Publication Country year	Country	Design	Controls	Number	Vitamin D dose	Curative effect	Safety	Jadad scores	References
Zendedel et al	2015	Iran	Single-center, double-blind, Placebo and randomized	Placebo	44 vs 44	Oral doses of 100,000 IU per month for 6 months	Decreased COPD exacerbation and improved FEV1in the patients with severe COPD	NA	3	^Citation41
Martineau et al	2015	UK	Multicenter, double-blind, and randomized	Placebo	118 vs 122	Six bimonthly oral doses of 120,000 IU	Effective against moderate or severe exacerbation in COPD patients with 25(OH)D deficiency	No serious adverse event	5	^Citation38
Bjerk et al	2013	USA	Single center and pilot randomized	Placebo	18 vs 18	Oral doses of 2,000 IU daily for 6 weeks	No discernible effect on a simple measure of physical performance	NA	1	^Citation40
Hornikx et al	2012	Belgium	Double-blind and randomized	Placebo	25 vs 25	A monthly dose of 100,000 IU for 1 year	Improvement in inspiratory muscle strength and maximal oxygen uptake	NA	4	^Citation39
Lehouck et al	2012	Belgium	Randomized	Placebo	91 vs 91	A monthly dose of 100,000 IU for 1 year	Reduced exacerbation in COPD patients with 25(OH)D deficiency	Four with mild and asymptomatic hypercalcemia	4	^Citation9

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; FEV₁, forced expiratory volume in 1 second; NA, not applicable.

Figure 2 Forest plots of the serum level of 25(OH)D in the controls and COPD patients.

Notes: Weights are from random-effects analysis. *Low-risk COPD: FEV₁%pred ≥50% and less than two treated exacerbation per year. ^#High-risk COPD: FEV₁%pred <50%, or two or more treated exacerbations per year, or one or more hospitalizations for COPD exacerbations per year.
Abbreviations: CI, confidence interval; FEV₁%pred, forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) predicted; SMD, standard mean difference.

Figure 3 Forest plots of the deficiency rate of serum 25(OH)D.

Notes: (A) Pooled analysis of the deficiency rates of 25(OH)D between controls and COPD patients in the cohort studies. Weights are from random-effects analysis. (B) Pooled analysis of the deficiency rates of 25(OH)D between the controls and COPD patients in the case-control studies. (C) Pooled analysis of the deficiency rates of 25(OH)D between the mild and moderate/severe COPD patients. (D) Pooled analysis of the deficiency rates of 25(OH)D between moderate and severe COPD patients. Weights are from random-effects analysis.
Abbreviations: 25(OH)D, 25-hydroxyvitamin D; CI, confidence interval; RR, relative ratio.

YangYMGuoYFZhangHSSunTYAntimicrobial peptide LL-37 circulating levels in chronic obstructive pulmonary disease patients with high risk of frequent exacerbationsJ Thorac Dis2015774074525973241

 PubMed Web of Science ®Google Scholar

YangHLongFZhangY1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease PatientsPLoS One201510e012051525905635

 PubMed Web of Science ®Google Scholar

MahlinCvon SydowHOsmancevicAVitamin D status and dietary intake in a Swedish COPD populationClin Respir J20148243223711108

 PubMed Web of Science ®Google Scholar

ZhouXHanJSongYZhangJWangZSerum levels of 25- hydroxyvitamin D, oral health and chronic obstructive pulmonary diseaseJ Clin Periodontol20123935035622296704

 PubMed Web of Science ®Google Scholar

DuckersJMEvansBAFraserWDStoneMDBoltonCEShaleDJLow bone mineral density in men with chronic obstructive pulmonary diseaseRespir Res20111210121812978

 PubMed Web of Science ®Google Scholar

XiaomeiWHangXLinglingLXuejunLBone metabolism status and associated risk factors in elderly patients with chronic obstructive pulmonary disease (COPD)Cell Biochem Biophys20147012913424633456

 PubMed Web of Science ®Google Scholar

PerssonLJAanerudMHiemstraPSHardieJABakkePSEaganTMChronic obstructive pulmonary disease is associated with low levels of vitamin DPLoS One20127e3893422737223

 PubMed Web of Science ®Google Scholar

JacksonASShrikrishnaDKellyJLVitamin D and skeletal muscle strength and endurance in COPDEur Respir J20134130931622556020

 PubMed Web of Science ®Google Scholar

JanssensWBouillonRClaesBVitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding geneThorax20106521522019996341

 PubMed Web of Science ®Google Scholar

LeeHMLiuMLeeKLuoYWongNDDoes low vitamin D amplify the association of COPD with total and cardiovascular disease mortality?Clin Cardiol20143747347824719373

 PubMed Web of Science ®Google Scholar

JungJYKimYSKimSKRelationship of vitamin D status with lung function and exercise capacity in COPDRespirology201520578278925868752

 PubMed Web of Science ®Google Scholar

PerssonLJAanerudMHiemstraPSVitamin D, vitamin D binding protein, and longitudinal outcomes in COPDPLoS One201510e012162225803709

 PubMed Web of Science ®Google Scholar

RommeEARuttenEPSmeenkFWSpruitMAMenheerePPWoutersEFVitamin D status is associated with bone mineral density and functional exercise capacity in patients with chronic obstructive pulmonary diseaseAnn Med201345919622462562

 PubMed Web of Science ®Google Scholar

ZendedelAGholamiMAnbariKGhanadiKBachariECAzargonAEffects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical Trial StudyGlob J Health Sci2015724324825946929

 PubMedGoogle Scholar

MartineauARJamesWYHooperRLVitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trialLancet Respir Med2015312013025476069

 PubMed Web of Science ®Google Scholar

BjerkSMEdgingtonBDRectorTSKunisakiKMSupplemental vitamin D and physical performance in COPD: a pilot randomized trialInt J Chron Obstruct Pulmon Dis201389710423430315

 PubMed Web of Science ®Google Scholar

HornikxMVan RemoortelHLehouckAVitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trialRespir Res2012138423006613

 PubMed Web of Science ®Google Scholar

LehouckAMathieuCCarremansCHigh doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trialAnn Intern Med201215610511422250141

 PubMed Web of Science ®Google Scholar