Table I.
Study (year) | Design | No. of patients | Mean or median age in years (range) | Drug/total daily dose | Treatment duration | Efficacy for primary outcome | Lung function (when reported) | Adverse effects |
---|---|---|---|---|---|---|---|---|
Schiotz et al.[49] (1983) | R, DB, PC, matched pairs | 26 | 14 (4–29) | BEC 400 μg | 16 wk | No effect on sputum inflammatory markers | FVC (mean, start of study → after treatment): PL 98% → 78%, BEC 89% → 91%, overall 90% → 85% No statistical tests reported | None reported |
Van Haren et al.[50] (1995) | DB, PC, CO | 12 | 26 (16–45) | BUD 1600 μg | 6 wk | Decreased airway reactivity in 58% (≥1 doubling dose increase in PC20 histamine). Small improvement in cough and dyspnea scores | No effect FEV1 (after treatment): PL 2.2 L, BUD 2.3 L, FVC: PL 3.3 L, BUD 3.6 L | None reported |
Nikolaizik and Schoni[51] (1996) | R | 49 | 19.8, SD 6.8 | BEC 1500 μg | 30 d | Positive effect on thoracic gas volume (p = 0.012). ICS had no effect on other measures | No effect FVC (mean, start of study → after treatment): no ICS 58% → 65%, ICS 55% → 65%, FEV1 (mean, start of study → after treatment): no ICS 40% → 48%, ICS 37% → 45% | No mention of AE reporting in paper |
Balfour-Lynn et al.[52] (1997) | R, DB, PC, CO | 23 | 10.3 (7–17) | FLU 400 μg | 6 wk | No improvement in sputum inflammatory markers | No effect FVC: baseline 75%, PL 78%, FLU 78%, FEV1: baseline 64 %, PL 67%, FLU 65% | Reported AEs: PL 15 (65%), FLU 18 (78%). Most URI/CF pulmonary exacerbations. Two possibly drug related: transient cough, rash |
Bisgaard et al.[53] (1997) | R, DB, parallel | 55 | 20 (not given) | BUD 1600 μg | 24 wk | Trend toward reduced decline in FEV1 | Intention to treat ΔFEV1: PL −0.187 L, BUD −0.032 L(p = 0.08) | PL 13, BUD 17 (overall incidences comparable) |
Dauletbaev et al.[54] (1999) | R, open label, parallel | 26 | 26 (16–38) | FLU 1000 μg | 3 wk | No improvement in clinical symptom score, lung function or sputum inflammatory markers | FEV1 (mean, start of study → after treatment): PL 57 → 56% p > 0.2, FLU 56 → 53% p > 0.1 | No clinical AEs reported. Sputum superoxide anion release was higher in FLU group (34 vs 25 nmol/h/106 cells p = 0.02) |
Wojtczak et al.[55] (2001) | Uncontrolled, prospective | 12 | 6 (1.5–13) | BEC 420 μg | 8 wk | Decreased BALF neutrophils (to 1/3 pretreatment levels, p = 0.03) | Not done as outcome measure | None reported. No increase in airway infection. No new Pseudomonas infections |
Balfour-Lynn et al.[56] (2006) | R, DB, PC, MC, withdrawal trial | 171 | 14.6 (6–48) [FLU] 15.8 (6–53) [PL] | FLU varied doses | 6 mo | No difference in time to first exacerbation, HR 1.07 (0.68–1.7) | FVC (mean, start of study → after treatment): PL 90% → 90%, FLU 90% → 90%, FEV1 (mean, start of study → after treatment): PL 74% → 73%, FLU 76% → 76% | 24 withdrawals from each group. 136 AE in FLU group (3 SAE: head injury, gallstones, intra-abdominal sepsis). 161 AE in PL group (0 SAE) |
De Boeck et al.[57] (2007) | R, DB, PC, MC | 27 | 8.2 (FLU) 9 (PL) | FLU 1000 μg | 12 mo | No difference in FEV1 | ΔFEV1 (prebronchodilator): PL −3.6%, FLU +3.9%, ΔFEV1 (post-bronchodilator): PL −3.9%, FLU +3.3% | Growth suppression: height gain PL 5.49 cm, height gain FLU 3.96 cm (p = 0.005). No increase in Pseudomonas infection or resp infections |
Ren et al.[58] (2008) | Observational | 2565 | 6–17 | Varied | 2 y | Decreased rate of decline of FEV1 in patients regularly using ICS (p = 0.04) | Rate of change of FEV1 (% pred/y) after ICS: patients using ICS −0.44%/y, comparison group not using ICS −1.44%/y | Decreased WFA and HFA z-scores, increased use of insulin or oral hypoglycemics, and increased rates of Stenotrophomonas maltophilia, Burkholderia cepacia, and Aspergillus spp. in ICS users |
AE= adverse event; BALF = bronchoalveolar lavage fluid; BEC= beclomethasone; BUD= budesonide; CO= crossover; DB= double-blind; FEV1 = forced expiratory volume in 1 second; FLU = fluticasone propionate; FVC= forced vital capacity; HFA= height for age; HR= hazard ratio; MC= multicenter; NS= not significant; PC= placebo-controlled; PC20 = concentration provoking a 20% decline in FEV1; PL = placebo; pred = prednisone; R= randomized; resp = respiratory; SAE= serious AE; URI = upper respiratory tract infection; WFA=weight for age; Δ indicates change; → indicates after intervention/treatment.