One-step individual participant data meta-analysis, rate of moderate or severe COPD exacerbations: overall and by subgroup
| N individuals (trials) | Event rate per participant-year, control group | Event rate per participant-year, intervention group | Adjusted incidence rate ratio (95% CI)* | P value | P value for interaction | |
| Overall | 469 (3) | 398/201.87 (1.97) | 381/205.66 (1.85) | 0.94 (0.78 to 1.13) | 0.52 | |
| Baseline 25(OH)D (nmol/L) | ||||||
| <25 | 87 (3) | 77/36.60 (2.10) | 51/41.52 (1.23) | 0.55 (0.36 to 0.84) | 0.006 | 0.015 |
| ≥25 | 382 (3) | 321/165.27 (1.94) | 330/164.13 (2.01) | 1.04 (0.85 to 1.27) | 0.71 | |
| GOLD spirometric grade | ||||||
| 1 or 2 | 252 (3) | 139/109.17 (1.27) | 137/111.11 (1.23) | 1.01 (0.75 to 1.35) | 0.94 | 0.59 |
| 3 or 4 | 217 (3) | 259/92.70 (2.79) | 244/94.55 (2.58) | 0.91 (0.72 to 1.16) | 0.44 | |
| Concomitant inhaled corticosteroid at baseline | ||||||
| No | 126 (3) | 63/49.94 (1.26) | 58/56.17 (1.03) | 0.93 (0.56 to 1.55) | 0.78 | 0.75 |
| Yes | 343 (3) | 335/151.93 (2.20) | 323/149.49 (2.16) | 0.96 (0.79 to 1.16) | 0.66 | |
| Body mass index (kg/m2) | ||||||
| <25 | 213 (3) | 210/103.67 (2.03) | 173/83.89 (2.06) | 1.03 (0.78 to 1.36) | 0.84 | 0.53 |
| ≥25 | 256 (3) | 188/98.20 (1.91) | 208/121.77 (1.71) | 0.89 (0.70 to 1.15) | 0.38 | |
| Frequency of vitamin D dosing | ||||||
| Intermittent bolus | 422 (2) | 374/189.75 (1.97) | 364/193.67 (1.88) | 0.96 (0.79 to 1.15) | 0.64 | 0.43 |
| Daily | 47 (1) | 24/12.12 (1.98) | 17/11.98 (1.42) | 0.74 (0.38 to 1.41) | 0.35 | |
| rs731236 (TaqI, VDR) genotype | ||||||
| TT | 142 (2) | 105/57.09 (1.84) | 119/71.18 (1.67) | 0.95 (0.70 to 1.31) | 0.77 | 0.52 |
| CT | 198 (2) | 184/89.80 (2.05) | 163/89.20 (1.83) | 0.90 (0.67 to 1.19) | 0.45 | |
| CC | 67 (2) | 65/37.75 (1.72) | 65/25.95 (2.51) | 1.28 (0.81 to 2.02) | 0.28 | |
| rs11568820 (cdx2, VDR) genotype | ||||||
| GG | 234 (2) | 190/105.35 (1.80) | 196/104.79 (1.87) | 0.99 (0.77 to 1.28) | 0.95 | 0.72 |
| GA | 149 (2) | 151/67.80 (2.23) | 130/71.22 (1.83) | 0.92 (0.68 to 1.25) | 0.59 | |
| AA | 20 (2) | 13/9.20 (1.41) | 12/7.86 (1.53) | 1.41 (0.55 to 3.66) | 0.48 | |
| rs7041 (HaeIII, DBP) genotype | ||||||
| GG | 106 (2) | 108/48.67 (2.22) | 106/47.72 (2.22) | 1.08 (0.78 to 1.49) | 0.66 | 0.15 |
| GT | 207 (2) | 157/88.47 (1.77) | 182/99.11 (1.84) | 1.05 (0.78 to 1.40) | 0.77 | |
| TT | 92 (2) | 89/46.18 (1.93) | 63/38.92 (1.62) | 0.75 (0.51 to 1.09) | 0.14 | |
| rs4588 (StyI, DBP) genotype | ||||||
| CC | 191 (2) | 175/91.53 (1.91) | 168/83.16 (2.02) | 1.05 (0.80 to 1.39) | 0.72 | 0.34 |
| CA | 184 (2) | 151/77.08 (1.96) | 158/90.00 (1.76) | 0.93 (0.70 to 1.24) | 0.61 | |
| AA | 35 (2) | 31/16.95 (1.83) | 25/14.45 (1.73) | 0.84 (0.41 to 1.73) | 0.64 | |
| Gc (DBP) genotype | ||||||
| Gc1/1 | 187 (2) | 172/89.45 (1.92) | 164/81.14 (2.02) | 1.07 (0.80 to 1.42) | 0.65 | 0.24 |
| Gc2/1 | 183 (2) | 151/77.08 (1.96) | 158/89.16 (1.77) | 0.93 (0.70 to 1.24) | 0.63 | |
| Gc2/2 | 32 (2) | 31/16.78 (1.85) | 18/12.62 (1.43) | 0.68 (0.29 to 1.58) | 0.37 | |
GOLD spirometric grade 1 or 2: FEV1 ≥50% predicted; grade 3 or 4: FEV1 <50% predicted. *, adjusted for age, sex, COPD severity and trial.
25(OH)D, 25-hydroxyvitamin D; DBP, vitamin D binding protein; Gc, group-specific component; GOLD, Global Initiative for Chronic Obstructive Lung Disease; VDR, vitamin D receptor.