European screening for α ₁ -antitrypsin deficiency in subjects with lung disease

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a common hereditary disorder that predisposes to early-onset pulmonary emphysema. Despite its prevalence, AATD is highly underdiagnosed. According to published guidelines for AATD, a diagnostic testing is greatly recommended in symptomatic adults with emphysema, COPD, or asthma with airflow obstruction incompletely reversible after aggressive bronchodilator treatment. Aim: To investigate AATD presence in ten European countries targeting a cohort of symptomatic subjects. Methods: Blood samples from adult subjects with lung disease were collected as dried blood spot (DBS). Detection testing algorithm consisted of 3 steps: first, all DBS specimens were analysed for α 1 -antitrypsin (AAT) levels by nephelometry; second, only samples with AAT levels below normal range (0.83 – 2.00 g/l) were genotyped for S- and Z-alleles by polymerase chain reaction; third DBS were phenotyped by isoelectric focusing in case of PiS, PiZ and non-S non-Z allele results. Results: A total of 5396 subjects from Bulgaria, Croatia, Hungary, Latvia, Lithuania, Romania, Russia, Slovakia, Slovenia and Ukraine were screened in 11 months. Seven hundred and eighty two (14.4%) had DBS AAT levels below the normal range. Among them, detection of S- and Z-alleles showed 16 PiZZ, 1 PiSS, 5 PiSZ, 38 PiS, 79 PiZ and 642 non-S non-Z variants. AAT phenotyping of PiZ, PiS and non-S non-Z alleles revealed 1 PiZrare, 38 PiMS, 78 PiMZ, 579 PiMM and 63 no result. Detection rate of severe AATD in symptomatic subjects was 0.41%. Conclusions: These data would support AATD screening programs in countries with a large number of symptomatic subjects but low awareness about this genetic condition.