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

Int J Chron Obstruct Pulmon Dis. 2009:4:443-52. doi: 10.2147/copd.s8577. Epub 2009 Dec 29.

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.

MeSH terms

  • Enzyme Replacement Therapy*
  • Female
  • Forced Expiratory Volume
  • Genotype
  • Humans
  • Injections, Intravenous
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Phenotype
  • Recovery of Function
  • Smoking Cessation
  • Spirometry
  • Time Factors
  • Tissue Banks
  • Treatment Outcome
  • alpha 1-Antitrypsin / administration & dosage*
  • alpha 1-Antitrypsin Deficiency / enzymology
  • alpha 1-Antitrypsin Deficiency / genetics
  • alpha 1-Antitrypsin Deficiency / physiopathology
  • alpha 1-Antitrypsin Deficiency / therapy*

Substances

  • alpha 1-Antitrypsin