Alpha-1 proteinase inhibitors for the treatment of alpha-1 antitrypsin deficiency: safety, tolerability, and patient outcomes

Figures & data

Table 1 Genotype variants in alpha-1 antitrypsin protein level and function

Variant	Allele or mutation	Features
Normal	M	Normal plasma levels (>20 μmol/L), protein variants exist (eg, M1, M2, etc)
Deficient	Z or S	Common deficiency variants: “Z” and “S”; plasma levels: 5–6 μmol/L and 8–11 μmol/L, respectively
Null	QOLisbon, QODublin, QOBolton, QOCork Thr68IIe exon II	No detectable circulating protein
Dysfunctional	Met358Arg	Pittsburgh mutation^Citation3: protein is thrombin, rather than elastase inhibitor

Table 2 Summary of clinical trials on alpha-1 antitrypsin augmentation therapy

Trial design	Trial reference	Year	Main outcome measures
Randomized	Dirksen et al^Citation42	1999	Slower rate of lung tissue loss on CT and no change in FEV1 decline
	Dirksen et al^Citation44	2009	Slower rate of lung tissue loss on CT
Observational	Stone et al^Citation80	1995	Reduction in urine desmosine levels
	Seersholm et al^Citation40	1997	Reduction in FEV1 decline in cohort with FEV1 35%–49%
	NHLBI registry	1998	Reduction in FEV1 decline in cohort with FEV1 35%–49%
	Lieberman^Citation81	2000	Reductions in exacerbations
	Wencker et al^Citation82	2001	Slower rate of FEV1 decline
	Tonelli et al^Citation83	2009	Slower rate of FEV1 decline
Descriptive	Gottlieb et al^Citation84	2000	No reduction in elastin degradation rate
	Stockley et al^Citation85	2002	Reduction in sputum LTB4

Note: Readers may also refer to Stoller et al⁸⁶ for more information.

Abbreviations: CT, computed tomography; FEV₁, Forced expiratory volume in 1 second; LTB4, Leukotriene B4; NHLBI, National Heart, Lung, and Blood Institute.

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