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Table 1 Studies on augmentation therapy

From: Alpha-1 antitrypsin deficiency: outstanding questions and future directions

Authors Dose Type of study End Point Results
Non-randomised studies
 Seersholm et al., 1999 [58] 60 mg/kg/7 days Observational, with control group
(n = 295)
FEV1 decline Less FEV1 decline in treated group (56 vs 75 ml/y; p = 0,02)
Greater benefit for patients with FEV1:31–65%
 American AAT Deficiency Registry Study Group, 1998 [50] 33%, weekly
43% biweekly
24% monthly
Observational, with control group
(n = 1129)
FEV1 decline
Mortality
Reduction of mortality (OR 0,64; p = 0,02)
Less FEV1 decline in patients with FEV1 35–49%, treated
(66 vs 93 mL/y; p = 0,03)
 Wencker et al., 2001 [59] 60 mg/kg/7 days Observational cohort. No control group (n = 96) FEV1 decline Less FEV1 decline during treatment (49,2 vs 34,2 mL/Y, p = 0,019). Lowest decline in FEV1 > 65% (256 vs 53 ml/Y, p = 0,001)
 Tonelli et al., 2009 [60]   Observational with control group (n = 164) FEV1 decline
Mortality
Increase in FEV1: 10.6 ± 21.4 mL/Y; p = 0.05).
No differences on mortality
Randomised studies
 Dirksen et al., 1999 [64] 250 mg/kg/28 days RCT (n = 66)
FEV1:30–80%
FEV1 decline, lung density No significant effects on lung function
Trend towards a favourable effect reducing loss of lung tissue
 Dirksen et al., 2009 [68] 60 mg/kg/7 days RCT (n = 77)
FEV1:25–80%
Lung function, QoL, exacerbations, lung density Reduction in loss of lung density measured by CT in treated patients (p = 0.049)
No differences on FEV1 or DLCO
No differences on exacerbations frequency
 Chapman et al., 2015 [72] 60 mg/kg/7 days RCT (n = 180)
Pi*ZZ, rare or null genotypes
AAT < 11 mM, Emphysema on CT, FEV1:35–70%
Lung function, QoL, exacerbations, lung density Reduction in loss of lung density measured by CT in treated patients(p = 0,03). No differences on FEV1 or DLCO. No differences in QoL
Meta-analysis
 Chapman el al, 2009 [70]   Meta-analysis of studies on treated patients vs controls form Canadian Registry (n = 1509) FEV1 decline Reduction of 26% on FEV1 decline (17,9 ml/Y) in patients on treatment with ev AAT. Effect due to subjects with FEV1: 30–65%
 Gotzsche and Johansen, 2010 [71] 60 mg/kg/7 days Meta-analysis Cochrane from 2 RCT (n = 140) FEV1 Decline
DLCO
Lung density
Exacerbations
Lower lung density loss in treated patients (p = 0.03)
No differences in lung function
No differences in exacerbations
 Stockley et al., 2010 [69] 60 mg/kg/7 days Integrated analysis of lung density studies Lung density loss
FEV1 decline
Lower lung density loss in treated patients (1.73 vs 2.74 g/L, p = 0.006)
No differences in FEV1 decline
Marciniuk et al., 2012 [63]   Meta-analysis of all studies including treated patients with ev AAT vs controls All parameters Reduction in lung density loss measured by CT.
Reduction on mortality
Studies on exacerbations
 Lieberman, 2000 [73] 55% weekly
37% biweekly
8% monthly
Observational
(online survey)
n = 89
Exacerbations frequency Reduction on exacerbations frequency from 3 to 5/year to 0–1/year on treatment with ev AAT
 Stockley et al., 2002 [74] 60mgs/kg/7 days Descriptive
(n = 12)
Inflammatory biomarkers in sputum Reduction of LTB4 after treatment
 Barros-Tizón et al., 2012 [75] 180 mg/kg/21 days Retrospective (pre-post AAT treatment) Frequency and severity of exacerbations Reduction on number and severity of exacerbations and hospital admissions related costs
  1. Adapted from Casas F et al. Arch Bronconeumol 2015; 51:185–192 (ref. [38])