Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank

Adriano R Tonelli, Farshid Rouhani, Ning Li, Pam Schreck, Mark L Brantly, Adriano R Tonelli, Farshid Rouhani, Ning Li, Pam Schreck, Mark L Brantly

Abstract

Introduction: Intravenous augmentation therapy with purified intravenous alpha-1 antitrypsin replaces the deficient protein and is the only currently approved treatment for alpha-1 antitrypsin deficiency (AATD) related lung disease. While augmentation therapy has been available for more than 20 years, there are a limited number of studies evaluating the effect of augmentation on lung function.

Material and methods: We examined the decline in forced expiratory volume in one second (FEV(1)) in patients enrolled in the Alpha-1 Foundation DNA and Tissue Bank in relation to the use or not of alpha-1 antitrypsin augmentation therapy. For the purpose of our analysis we included 164 patients with AATD and PI ZZ genotype.

Results: Mean age of the patients was 60 years, 52% were females, 94% were white and 78% ex-smokers. The mean FEV(1) at baseline was 1.7 L and the mean FEV(1) % of predicted was 51.3%. The mean follow-up time was 41.7 months. A total of 124 (76%) patients received augmentation therapy (augmented group) while 40 patients (24%) did not received it (non-augmented group). When adjusted by age at baseline, sex, smoking status, baseline FEV(1) % of predicted, the mean overall change in FEV(1) was 47.6 mL/year, favoring the augmented group (DeltaFEV(1) 10.6 +/- 21.4 mL/year) in comparison with the non-augmented group (DeltaFEV(1) -36.96 +/- 12.1 mL/year) (P = 0.05). Beneficial DeltaFEV(1) were observed in ex-smokers and the group with initial FEV(1) % of predicted of <50%. No differences were observed in mortality.

Conclusions: In conclusion, augmentation therapy improves lung function in subjects with AATD when adjusted by age, gender, smoking status and baseline FEV(1) % of predicted. The beneficial effects were noted in ex-smoker subjects with FEV(1) below 50% of predicted.

Keywords: alpha-1 antitrypsin deficiency; augmentation therapy; forced expiratory volume in one second.

Figures

Figure 1
Figure 1
Flow diagram of study population analysis.
Figure 2
Figure 2
ΔFEV1 (mL/year) in augmented and non-augmented patients by initial FEV1 % of predicted (>65%, 30% to 65% and <30%). *P = 0.0006, **P = 0.07.
Figure 3
Figure 3
ΔFEV1 (mL/year) in augmented and non-augmented patients by initial FEV1 % of predicted (<50% and ≥50%).*P = 0.026.
Figure 4
Figure 4
ΔFEV1 (mL/year) in augmented and non-augmented patients by smoking status *P = 0.05.

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