Table 2.

Studies of α₁-antitrypsin replacement therapy

Author(s)	Study type	Primary (secondary) outcome measure(s)	Salient results
Non-randomized studies
Seersholm et al80	Observational study with concurrent controls	FEV1 decline	– Slower FEV1 decline in treated group Most marked benefit in those with FEV1 31%–65% predicted
NHLBI study81	Observational study with concurrent controls	FEV1 decline; Mortality	– No overall difference in FEV1 decline Slower FEV1 decline in those with FEV1 30%–64% predicted Faster decline in those with FEV1 > 75% predicted – Decreased mortality in treated group
Wencker et al82	Observational study of patients pre- and during treatment	FEV1 decline	– Overall slower FEV1 decline on treatment Most significant benefit in those with FEV1 > 65% no significant difference in those with FEV1 30%–65%
Tonelli et al83	Observational study with concurrent controls	FEV1 decline (mortality)	– Slower decline in treated group if FEV1< 50% predicted and ex-smoker. Faster decline in treated group if FEV1 > 60%. – No difference in mortality
RCTs
Dirksen et al84	Double-blind placebo controlled RCT	FEV1/DLCO decline, (CT densitometry)	– No difference in FEV1 or DLCO – Trend towards slower annual loss of lung density in treated group
Dirksen et al86	Double-blind placebo controlled RCT	CT densitometry (lung function, health status, exacerbations)	– Trend towards reduction in lung density loss in treated group – No difference in FEV1 or DLCO – No difference in exacerbation rate but exacerbations less severe in treated group
Meta-analyses
Gøtzsche and Johansen22	Review of RCTs	Mortality, FEV1 decline	– Reduction in lung density loss in treated group over whole trial period – Trend towards faster FEV1 decline in treated group (P = 0.06)
Stockley et al90	Integrated analysis of RCTs	CT densitometry, FEV1 decline	– Reduction in lung density loss in treated group (P = 0.006) – Trend towards faster FEV 1 decline in treated group (P = 0.321)
Studies on exacerbations
Lieberman91	Patient survey	Exacerbation frequency	– Reduction in exacerbation frequency from 3–5 per annum to 0–1 per annum following initiation of treatment
Stockley et al93	Clinical study using BAL from patients on α1-antitrypsin replacement	Sputum inflammatory markers	– Sputum LTB4 significantly reduced following weekly 60 mg/kg α1-antitrypsin replacement. – Non-significant reductions in IL-8 and MPO

Abbreviations: BAL, bronchoalveolar lavage fluid; D_LCO, diffusing capacity of the lung for carbon monoxide; CT, computed tomography; FEV_1, forced expiratory volume in 1 second; IL-8, interleukin 8; LTB₄, leukotriene B4; MPO, myeloperoxidase; NHLBI, national heart lung and blood institute; RCTs, randomized controlled trials.