Journal Article

Real world evaluation of a novel lateral flow assay (AlphaKit® QuickScreen) for the detection of alpha-1-antitrypsin deficiency

Vogelmeier, Claus F., Miravitlles, Marc, Klemmer, Andreas, Rodríguez-Frias, Francisco, Greulich, Timm, Belmonte, Irene

2018

Overview

Background Alpha-1-Antitrypsin (AAT) deficiency (AATD) is a hereditary disorder that manifests primarily as pulmonary emphysema and liver cirrhosis. The clinically most relevant mutation causing AATD is a single nucleotide polymorphism Glu342Lys (Z-mutation). Despite the recommendation to test every COPD patient, the condition remains severely underdiagnosed with a delay of several years between first symptoms and diagnosis. The Grifols’ AlphaKit® QuickScreen is a novel qualitative point-of-care (POC) in vitro screening test developed for the detection of the Z AAT protein in capillary whole blood. The objective of this prospective, international, multi-center, diagnostic, interventional real-world study was to assess the performance of this device for the detection of AATD in test-naïve COPD patients. Methods 1044 test-naïve COPD patients were recruited from 9 centers in Spain and 10 centers in Germany, ranging from primary to tertiary care. To evaluate the performance of the test, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated compared with the gold standard (genotyping). Results Genotyping and phenotyping of all 1019 evaluable samples revealed 4.12% of patients as carriers of at least one Z-allele, while 0.29% carried the homozygous genotype Pi*ZZ. The evaluation of the test’s ability to detect the PiZ protein yielded the following results: specificity 97.8%, sensitivity 73.8%, negative predictive value 98.9%, and positive predictive value 58.5%. All false negatives ( n  = 11) were heterozygote Pi*MZ samples. Conclusions The tested device can be used as an appropriate tool to exclude AATD in primary care and in the overall COPD population, except in patients with a high a-priori- probability of AATD.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Aged / Alpha 1-antitrypsin deficiency / alpha 1-Antitrypsin Deficiency - blood / alpha 1-Antitrypsin Deficiency - diagnosis / alpha 1-Antitrypsin Deficiency - epidemiology / Bioassay / Chronic obstructive pulmonary disease / Cirrhosis / COPD / Diagnosis / Diagnostic systems / Emphysema / Female / Gene mutation / Gene polymorphism / Genotyping / Germany - epidemiology / Health care / Heterozygotes / Humans / Immunoassay - methods / Immunoassay - standards / In vitro methods and tests / Internationality / Laboratories / Lateral flow assay / Liver / Liver cirrhosis / Male / Mass Screening - methods / Mass Screening - standards / Medicine / Medicine & Public Health / Middle Aged / Mutation / Patients / Performance assessment / Performance evaluation / Phenotyping / Pneumology/Respiratory System / Polymorphism / Primary care / Prospective Studies / Proteins / Pulmonary Disease, Chronic Obstructive - blood / Pulmonary Disease, Chronic Obstructive - diagnosis / Pulmonary Disease, Chronic Obstructive - epidemiology / Screening / Sensitivity analysis / Signs and symptoms / Single-nucleotide polymorphism / Spain - epidemiology