Results of a case-detection programme for α1-antitrypsin deficiency in COPD patients

alpha(1)-Antitrypsin (alpha(1)-AT) deficiency is an underdiagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The present authors have conducted a nationwide case detection programme of alpha(1)-AT deficiency in unselected patients with COPD using dried blood spots. The first phase analysed samples from 971 patients by determining alpha(1)-AT concentrations and identifying the deficient Z allele by genotyping using rapid real-time PCR. The second phase analysed 1,166 samples with alpha(1)-AT concentrations and identified both the S and the Z allele, but only in samples with low alpha(1)-AT concentrations. A total of eight (0.37%) individuals with the severe deficiency PiZZ were detected. In addition, three patients were identified with the PiSZ genotype in the second phase (0.3%). The global cost of the programme was E41,512, which represents 19.42 Euro per sample and 5,189 Euro per PiZZ detected. A sensitivity analysis demonstrated that performing Z genotype to all samples would have resulted in increased costs of 28 Euro per sample and 7,479.5 Euro per PiZZ case identified. In conclusion, a case detection programme of alpha(1)-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood spots is feasible and at a reasonable cost per case detected. Diagnostic yield and costs depend largely on inclusion criteria and the protocol for processing of samples.