Table 1.
Characteristics of RCTs
| Reference | Number of pts, length of ICS therapy (months), previous use of OCS and/or ICS | Mean age | Gender (%) | M/F ratio | % current and ex-smokers | Definition of former smokers | Ethnicity | Geographic area | Mean FEV1 (pre-post bd) absolute value in liters (% predicted) | ICS and dosage | Baseline bone mass density | Vit D before | Vit D during | Bone fractures |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Renkema et al, Chest 199622 | 58 24 No |
Bud 56 Bud+Pred 58 pla 54 |
m (100%) | 0 | cs Bud 43 Bud+Pred 47 pla 44 |
Stopped smoking at least 1 year before | nr | Netherlands | Pre bd Bud 2.16 L (67%) Bud+Pred 1.86 L (61) pla 1.90 L (60) |
Bud 1,600 μg/d Bud+Pred 1,600 μg/d +5 μg/d |
nr | nr | nr | nr |
| Vestbo et al, Lancet 199925 | 290 36 No in previous 6 months |
Bud 59 pla 59.1 |
Bud m 58.6 pla m 62.1 |
1.52 | cs Bud 75.9 pla 77.2 |
nr | nr | Denmark | Post bd Bud 2.36 L (86.2) pla 2.39 L (86.9) |
Bud 1,200 μg/d (6 months), then Bud 800 μg/d (30 months) | nr | nr | nr | nr |
| Weir et al, Clin Exp Allergy 199933 | 98 24 No |
BdP 65.5 pla 67.6 |
BdP m 65.3 pla m 83.6 |
2.92 | cs BdP 34.7 pla 42.8 es BdP 63.2 pla 57.1 |
nr | nr | UK | BdP pre bd 1.07 L (39.7) Post bd1.19 L pla Pre bd 1.13 L (41.4) Post bd 1.26 L |
BdP 750 μg bid <50 kg 1,000 μg bid >50 kg |
nr | nr | nr | nr |
| Pauwels et al, N Engl J Med 199921 | 1,277 36 No in previous 6 months |
Bud 52.5±7.5 pla 52.4±7.7 |
Bud m 73.5 pla m 72.2 |
2.60 | 100 | nr | nr | Belgium, Denmark, Finland, Italy, Netherlands, Norway, Spain, Sweden, UK | Pre bd Bud 2.53±0.64 L (76.8) pla 2.54±0.64 L (76.9) |
Bud 400 μg bid | Measured on 194 subjects. No change over time and no effect of treatment on bone density, except for a small, significant difference at the femoral trochanter in favor of budesonide | nr | nr | Baseline Vertebral Bud 13.4%; pla 11.5% End study Bud +8; pla +3 (P=0.50) |
| Lung Health Study Research Group, N Engl J Med 200034 | 1,116 40 (mean) No in previous year |
TA 56.2±6.8 pla 56.4±6.8 |
TA f 36% pla f 37.9% |
1.70 | cs TA 90.5 pla 89.8 |
Smoking cessation for over 2 years | Non-white TA 6.3% pla 4.1% |
USA | TA pre bd 2.16 L (65) Post bd 2.28 L (68.5) pla pre bd 2.10 L (63.4) Post bd 2.22 L (67.2) |
TA 600 μg bid | Measured at lumbar spine on 328 subjects, and at femoral neck on 359 subjects. After 3 years higher percentage decrease of bone density in those taking TA |
nr | nr | nr |
| Burge et al, BMJ 200026 | 751 36 FP 51% pla 57% |
FP 63.7 pla 63.8 |
FP m 75 pla m 74 |
2.93 | cs FP 36.4 pla 39.2 es FP 46.8 pla 45.8 |
nr | nr | UK | Post bd FP 1.42 L (0.47) pla 1.40 L (0.49) |
FP 500 μg bid | nr | nr | nr | FP 9 pla 17 2% both groups |
| Calverley et al, Lancet 200327 | 1,465 12 nr No in 4 weeks prior to study |
FP 63.5 pla 63.4 |
FP m 70 pla m 75 |
2.61 | cs FP 47 pla 53 |
nr | nr | UK | FP pre bd 1.26 L (45.0) Post bd 2.36 L pla 1.27 L (44.2) pla post bd 1.38 L |
FP 500 μg bid | nr | nr | nr | nr |
| Calverley et al, Eur Respir J 200320 | 1,022 12 nr |
Bud 64 pla 65 |
Bud m 74 pla m 75 |
3.07 | cs Bud 39 pla 30 |
nr | nr | Africa, Asia, Europe | Bud 1±0.32 L (36) pla 0.98±0.33 L (36) | Bud 400 μg/d | nr | nr | nr | nr |
| van Grunsven et al, Respir Med 200329 | 48 24 nr |
FP 46 pla 47 |
FP m 50% pla m 54% |
1.08 | cs FP 50 pla 50 |
nr | nr | Netherlands | FP pre bd 3.05 L (95) Post bd 3.16 L (98) pla pre bd 3.17 L (98) Post bd 3.19 L (99) |
FP 250 μg bid | nr | nr | nr | nr |
| Szafranski et al, Eur Respir J 200324 | 812 12 Bud 24% pla 26% |
Bud 64 pla 65 |
Bud m 64% pla m 65% |
1.27 | cs Bud 36 pla 34 |
nr | nr | Argentina, Brazil, Denmark, Finland, Italy, Mexico, Poland, Portugal, South Africa, Spain, UK | Bud 1.01 L (37) pla 0.98 L (36) |
Bud 200 μg bid | nr | nr | nr | nr |
| Calverley et al, N Engl J Med 20079 | 6,112 36 FP 20% pla 22% |
FP 65 pla 65 |
FP m 75 pla m 76 |
3.12 | cs FP 43 pla 43 |
nr | mixed | Europe, Asia-Pacific, USA | FP pre bd 1.12±0.39 L (44.1) Post bd 1.22±0.41 L pla pre bd 1.12±0.40 L (44.1) Post bd 1.22±0.42 L |
FP 500 μg bid | nr | nr | nr | Total, whole duration of the study FP 5.4% pla 5.1% |
| Calverley et al, Respir Res 200830 | 911 12 No in 6 weeks prior to study |
MF-DPI 800 μg 65.3 MF-DPI 400 μg 65 pla 65 |
MF-DPI 800 μg m 69% MF-DPI 400 μg m 67% pla m 69% | 2.15 | cs 28.3 | Quitting smoking ≥12 months before the study | MF-DPI 800 μg white 88% MF-DPI 400 μg white 86% pla white 85% |
UK | MF 800 μg qd pm pre bd 1.32 L (43) Post bd 1.45 L (47) MF 400 μg bid pre bd 1.25 L (42) Post bd 1.38 L (469) pla pre bd 1.26 L (42.1) Post bd 1.41 L (47) |
MF 800 μg qd pm 400 μg bid |
nr | nr | nr | ≤1% in groups |
| Shaker et al, COPD 200923 | 254 24–48 No in 6 months prior to study |
Bud 63.6 pla 63.6 |
Bud m 62 pla m 54 |
1,39 | cs 100 | nr | Ca | Denmark, Netherlands | Post bd Bud 1.53 L (51) pla 1.53 L (53) |
Bud 400 μg bid | nr | nr | nr | nr |
| Lapperre et al, Ann Intern Med 200928 | 114 30 No in 6 months prior to study |
FP 6m 64 FP 30m 62 pla 59 |
FP 6m m 84.6 FP 30m m 88.4 pla 83.3 |
6.21 | cs FP 30 months 61.5 FP 6 months 53.8 pla 70.8 |
nr | Nr | Netherlands | FP 30 months pre bd (57); post bd (64) FP 6 months pre bd (59); post bd (65) pla pre bd (54); post bd (61) |
FP 500 μg bid for 30 months FP 500 μg bid for 6 months |
nr | nr | nr | nr |
| Tashkin et al, Int J Chron Obstruct Pulmon Dis 201231 | 1,055 12 nr |
MF400 60.2 pla 58.8 |
MF400 m 78% pla m 78% |
3.22 | cs MF 44; pla 46 es MF 56; pla 54 |
nr | ca: 71.9% as: 16.9% mr: 9.4% |
Africa, Asia, Europe, North, Central, South America | MF 1.255 L pla 1.227 L |
MF 400 μg bid | nr | nr | nr | MF 3 (radio, facial bone, rib) pla 1 (foot) |
| Doherty et al, Int J Chron Obstruct Pulmon Dis 201232 | 1,196 12 No in previous 4 weeks |
MF 60.5 pla 58.8 |
MF m 78 pla m 75 |
3.04 | cs MF 53; pla 51 es MF 47; pla 49 |
≥10 pack/year history | MF white 70% pla white 66% |
USA | MF post bd 40.2±11.7 pla post bd 38.5±11.5 |
MF 400 μg bid | nr | nr | nr | nr |
| Vestbo et al, Lancet 201635 | 16,485 20 FF 33% pla 33% |
FF 65 pla 65 |
FF m 74 pla m 75 |
3.92 | cs FF 47 pla 47 |
nr | ca: 81% as: 17% |
Africa, Asia, Australia, Europe, North, Central, South America | post bd FF 1.70 (59.6) pla 1.70 (59.7) |
FF 92 μg qd | nr | nr | nr | FF 79 (2%) pla 78 (2%) |
Abbreviations: as, Asian; bd, bronchodilator; BdP, beclomethasone dipropionate; bid, twice a day; Bud, budesonide; ca, Caucasian; cs, current smokers; DPI, dry powder inhaler; es, ex-smokers; f, females; FEV1, forced expiratory volume in 1 s; FF, fluticasone furoate; FP, fluticasone propionate; ICS, inhaled corticosteroid; m, males; MF, mometasone furoate; mr, multiracial; nr, not reported; OCS, oral corticosteroid; pla, placebo; Pred, prednisolone; pm, evening; pt, patient; qd, once a day; RCT, randomized controlled trial; TA, triamcinolone acetonide; Vit, vitamin.