The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis

Figures & data

Table 1 Characteristics of included studies

Author	Year	Study design	Country, latitude degree	Sample size		BMI	Assay method	Serum 25(OH)D level (ng/mL)		Distribution of vitamin D deficiency (yes, %)
				COPD	Control			COPD	Control	COPD	Control
Janssens et al^Citation18	2010	Case–control	Belgium, middle latitude	262	152	25–30	RIA	All: 19.9±8.2; I (70)22.4; II (87) 20.35; III (75) 18.8; and IV (30) 16.0	24.6±8.7	All: 136 (51.91); I:27 (38.57); II:41 (47.13); III: 45 (60.00); and IV 23 (76.67)	47 (30.92)
Duckers et al^Citation19	2011	Case–control	UK, middle latitude	30	15	25–30	Immunoassay	Geometric mean (SD) 11.4 (1.9)	16.1 (1.4)	24 (80.00)	9 (60.00)
Persson et al^Citation20	2012	Case–control	Western Norway, high latitude	433	325	<25	LC–MS/MS	All: 25.2±10.0; II (199) 28.1±9.8; III (182) 22.7±9.3; IV(52) 21.6±10.0; AECOPD (359) 25.4±9.9; and SCOPD (74) 23.7±10.5	25.0±9.5	143 (33.03)	110 (33.85)
Quint et al^Citation21	2012	Cohort	UK, middle latitude	58	–	25–30	Immunoassay	AECOPD (58) 13.34±15.79 and SCOPD (58) 14.50±18.27	–	–	–
Zhou et al^Citation22	2012	Case–control	People’s Republic of China, middle latitude	193	181	<25	ELISA	12.86±4.3	14.34±4.97	182 (94.3)	156 (86.19)
Zhang et al^Citation38	2012	Case–control	People’s Republic of China, low latitude	74	30	<25	ELISA	–	–	AECOPD: 19 (52.78) and SCOPD: 15 (39.47)	5 (16.67)
Berg et al^Citation23	2013	Case–control	USA, middle latitude	348	150	25–30	LC–MS/MS	All: 22.9±11.99; II (116) 24.6±11.9; III (116) 21.9±11.9; and IV (116) 22.2±12.1	26.7±11.93	–	–
Holmgaard et al^Citation24	2013	Cohort	Denmark, middle latitude	462	–	<25	LC–MS/MS	All: 21.35±14.92; II (118) 21.96±14.53; III (239) 21.08±14.38; and IV (105) 21.96±16.14	–	–	–
Huang et al^Citation32	2013	Case–control	People’s Republic of China, low latitude	90	38	NA	ELISA	All: 27.74±18.72; AECOPD (46) 21.56±14.03; and SCOPD (44) 34.21±20.87	76.44±53.26	AECOPD: 24 (52.17) and SCOPD: 16 (36.36)	6(15.79)
Tan et al^Citation35	2013	Case–control	People’s Republic of China, middle latitude	104	100	<25	ELISA	23.58±8.51	27.62±6.59	39 (37.50)	16 (16.00)
Zhang et al^Citation31	2014	Case–control	People’s Republic of China, low latitude	78	30	<25	ELISA	AECOPD (38) 22.72±13.10 and SCOPD (40) 34.35±21.82	71.62±5.53	–	–
Lee et al^Citation25	2014	Case–control	USA, middle latitude	1,869	5,877	25–30	NA	–	–	All: 689 (38.69); I: 403 (44.93); and II–IV: 286 (32.35)	1,813 (32.04)
Puhan et al^Citation26	2014	Cohort	Switzerland and the Netherlands, middle latitude	356	–	NA	Immunoassay	II (234) 15.5±8.6; III (87) 15.5±9.7; and IV (35) 15.4±8.6	–	RR (95% CI): 1.01 (0.77–1.57)	–
Wang et al^Citation27	2014	Case–control	People’s Republic of China, low latitude	50	50	<25	Immunoassay	13.6±5.7	13.0±5.7	44 (88.00)	45 (90.00)
Lu et al^Citation33	2014	Case–control	People’s Republic of China, low latitude	126	50	NA	ELISA	All: 20.9±4.2; I (58) 22.2±3.4; II (39) 22.4±3.8; III (25) 16.5±1.9; and IV(4) 14.3±3.5	27.9±5.5	–	–
Lu et al^Citation34	2014	Case–control	People’s Republic of China, middle latitude	56	30	NA	ELISA	28.41±18.34	65.43±33.62	19(33.93)	3 (10.00)
Ye et al^Citation36	2014	Cohort	People’s Republic of China, low latitude	62	–	NA	Immunoassay	AECOPD (62) 15.24±6.39 and SCOPD (62) 18.99±4.68	–	–	–
Heidari et al^Citation28	2015	Case–control	Iran, middle latitude	90	100	NA	ECL	25±7.92	23±30.17	14 (15.56)	46 (46.00)
Said and Abd-Elnaeem^Citation37	2015	Case–control	Egypt, low latitude	61	20	<25	Immunoassay	33.53±19.33	44.4±9.1	10 (16.39)	0(0)
Yumrutepe et al^Citation25	2015	Cross–sectional	Turkey, middle latitude	90	57	25–30	RIA	14.5±11.06	16.8±10	–	–
Persson et al^Citation30	2015	Cohort	Western Norway, high latitude	426	–	NA	LC–MS/MS	–	–	II: 39 (19.70); III: 76 (42.56); and IV: 27 (55.10)	–

Note: The COPD severity is based on the GOLD classification.

Abbreviations: AECOPD, acute exacerbation COPD; BMI, body mass index; ECL, electrocheminluminescence; ELISA, enzyme–linked immunosorbent assay; LC–MS/MS, liquid chromatography electrospray ionization tandem mass spectrometry; NA, not available; RIA, radioimmunometric assay; RR, relative risk; SCOPD, stable COPD.

Figure 1 Flow chart of study selection.

Abbreviation: CNKI, Chinese National Knowledge Infrastructure.

Figure 2 Meta-analysis of serum vitamin D levels in COPD patients compared with controls.

Note: Stratified analysis based on latitude degree.
Abbreviations: SMD, standardized mean difference; CI, confidence interval.

Figure 3 Meta-analysis of vitamin D deficiency in COPD patients compared with controls.

Note: Stratified analysis based on assay methods.
Abbreviations: OR, odds ratio; CI, confidence interval; LC-MS/MS, liquid chromatography electrospray ionization tandem mass spectrometry; ELISA, enzyme-linked immunosorbent assay; NA, not available.

Figure 4 Meta-analysis of serum vitamin D levels in severe–very severe COPD patients compared with mild–moderate COPD patients.

Abbreviations: SMD, standardized mean difference; CI, confidence interval.

Figure 5 Meta-analysis of serum vitamin D levels in AECOPD patients compared with stable COPD patients.

Abbreviations: AECOPD, acute exacerbation COPD; SMD, standardized mean difference; CI, confidence interval.

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