DOES ALPHA(1)-ANTITRYPSIN AUGMENTATION THERAPY SLOW THE ANNUAL DECLINE IN FEV1 IN PATIENTS WITH SEVERE HEREDITARY ALPHA(1)-ANTITRYPSIN DEFICIENCY

Patients with severe hereditary alpha(1)-antitrypsin deficiency (alpha (1)-ATD) face a high risk of developing emphysema at a young age, Intr avenous augmentation therapy with purified human alpha(1)-antitrypsin (alpha(1)-AT) is now available, However, a controlled trial to show it s efficacy has never been carried out, The aim of this study was to co mpare the decline in forced expiratory volume in one second (Delta FEV 1) between Danish patients who had never received augmentation therapy and German patients treated with weekly infusion of alpha(1)-AT. From the files of the Danish alpha(1)-ATD register, 97 exsmokers, with a P iZ pheno-type and for whom results of at least two lung function measu rements with an interval of at least 1 yr were available, were identif ied, From a German group of patients treated with weekly infusions of alpha(1)-AT, 60 mg.kg(-1) body weight, 198 exsmokers, with biannual lu ng function measurements were identified, The Delta FEV1 was compared between the two treatment groups by random effects modelling, The Delt a FEV1 in the treated group was significantly lower than in the untrea ted group, with annual declines of 53 mL.yr(-1) (95% confidence interv al (95% CI) 48-58 mL.yr(-1)) and 75 mL.yr(-1) (95% Cl 63-87 mL.yr(-1)) , respectively (p=0.02), The two groups differed with respect to gende r and initial FEV1% predicted, Gender did not have any influence on th e Delta FEV1. Stratification by initial FEV1% pred showed a significan t effect of the treatment only in the group of patients,vith an initia l FEV1% pred of 31-65%, and Delta FEV1 was reduced by 21 mL.yr(-1). Th is nonrandomized study suggests that weekly infusion of human alpha(1) -antitrypsin in patients with moderately reduced lung function may slo w the annual decline in forced expiratory volume in one second.