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Multicenter Study
. 2018 Aug 13;19(1):151.
doi: 10.1186/s12931-018-0826-8.

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

Timm Greulich  1   2   3 , Francisco Rodríguez-Frias  4   5 , Irene Belmonte  4 , Andreas Klemmer  6   7 , Claus F Vogelmeier  6   7 , Marc Miravitlles  8
Affiliations
Multicenter Study

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

Timm Greulich et al. Respir Res. .

Abstract

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.

Keywords: Alpha-1-antitrypsin deficiency; COPD; Chronic obstructive pulmonary disease; Lateral flow assay; Screening.

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Conflict of interest statement

The study was approved by the ethics committee at the University of Marburg for all centers in Germany, and by the ethics committee at the University Hospital Vall d’Hebron in Barcelona for all centers in Spain.

Only patients who signed the informed consent form were included in the study.

Not applicable.

The study was sponsored by Grifols (Colmarer Straße 22, Frankfurt, Germany), manufacturer of AlphaKit® Quickscreen.

TG reports personal fees from Astra Zeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, GlaxoSmithKline, Novartis. He reports grants and personal fees from Grifols.

FR-F reports no conflicts of interest.

IB reports no conflicts of interest.

AK reports no conflicts of interest.

CFV reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis. He reports personal fees from CSL Behring, Chiesi, Menarini, Mundipharma, Teva, Cipla.

MM has received speaker fees from Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Grifols and Novartis, and consulting fees from Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Gebro Pharma, CSL Behring, Novartis and Grifols.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The testing algorithm is summarized. In both countries (Spain and Germany), the initial analysis consisted of the screening device (AlphaKit® QuickScreen) and the acquisition of blood on DBS (dried blood spot – AlphaKit). If the DBS-derived AAT serum level was ≥110 mg/dl and genotyping for the Z- and S-allele was negative, AATD was considered as excluded. All other samples underwent phenotyping to obtain a final result. DBS: dried blood spot; WBS: whole blood sample
See this image and copyright information in PMC

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