Diagnostic Performance of a Lateral Flow Assay for the Detection of Alpha-1-Antitrypsin Deficiency

Lόpez-Campos, José Luís; Hernández, Laura Carrasco; Márquez-Martín, Eduardo; Ruiz, Francisco Órtega; Delgado, Beatriz Martínez

doi:10.1016/j.arbr.2019.09.006

Cited by 3 publications

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“…The diagnosis of AATD continues to be a challenge for clinicians due to the low degree of suspicion and the lack of availability of rapid, simple circuits that permit more universal access to genotyping techniques aimed at diagnosing the disease [6][7][8]. This new diagnostic circuit represents an opportunity to improve the underdiagnosis of this clinical condition.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

et al. 2022

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Introduction Currently, strategies for improving alpha1 antitrypsin deficiency (AATD) diagnosis are needed. Here we report the performance of a multinational multiplex-based genotyping test on dried blood spots and buccal swabs sent by post or courier and with web registration for subjects with suspected AATD in Argentina, Brazil, Chile, Colombia, Spain, and Turkey. Methods This was an observational, cross-sectional analysis of samples from patients with suspected AATD from March 2018 to January 2022. Samples were coded on a web platform and sent by post or courier to the central laboratory in Northern Spain. Allele-specific genotyping for the 14 most common mutations was carried out with the A1AT Genotyping Test (Progenika-Grifols, Spain). SERPINA1 gene sequencing was performed if none of the mutations were found or one variant was detected in heterozygous status and the AAT serum level was < 60 mg/dl, or if requested by the clinician in charge. Results The study included 30,827 samples: 30,458 (94.7%) with final results after direct genotyping and 369 (1.1%) with additional gene sequencing. Only 0.3% of the samples were not processed due to their poor quality. The prevalence of the most frequent allele combinations was MS 14.7%, MZ 8.6%, SS 1.9%, SZ 1.9%, and ZZ 0.9%. Additionally, 70 cases with new mutations were identified. Family screening was conducted in 2.5% of the samples. Samples from patients with respiratory diseases other than COPD, including poorly controlled asthma or bronchiectasis, also presented AATD mutations. Conclusions Our results confirm the viability of this diagnostic system for genotyping AATD conducted simultaneously in different countries. The system has proved satisfactory and can improve the timely diagnosis of AATD.

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Section: Discussionmentioning

confidence: 99%

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

et al. 2022

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“…Interestingly the percentage of males is now reduced to 54%, while the mean age has increased to 53 years and mean FEV1(%) to 81%. This increase in the mean FEV1(%) may, in part, be due to the improvement in population and family screening, earlier detection of carriers and early diagnosis of lung diseases in individuals affected (18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Demographic and clinical characteristics of patients with α₁-antitrypsin deficiency genotypes PIZZ and PISZ in the Spanish registry of EARCO

et al. 2022

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BackgroundThe Spanish registry of alpha-1 antitrypsin deficiency integrated in the European alpha-1 antitrypsin deficiency research collaboration (EARCO) provides information about the characteristics of patients, in particular those with the PI*SZ genotype, which is frequent in Spain.MethodIndividuals with severe AATD defined as proteinase inhibitor (PI) genotypes PI*ZZ, PI*SZ and other rare deficient variants were included from February 1st, 2020, to February 1st, 2022. The analysis focuses on the comparison of the characteristics of Pi*ZZ and Pi*SZ participants.Results409 individuals were included, 53.8% were men, mean age of 53.5 years (standard deviation (sd): 15.9). Genotypes were PI*ZZ in 181 (44.7%), PI*SZ in 163 (40.2%), PI*SS in 29 (7.2%) and others in 32 (7.9%). 271 (67.4%) had lung disease; 175 COPD (43.5%), 163 emphysema (40.5%) and 83 bronchiectasis (20.6%). Individuals with the PI*SZ genotype were younger, more frequently non-index cases and had a lower frequency of respiratory diseases except asthma compared with PI*ZZ. Among patients with respiratory diseases, PI*SZ individuals were significantly older both at onset of symptoms and at diagnosis, only asthma was more frequent in PI*SZ than in PI*ZZ subjects. Twelve (15.4%) PI*SZ patients received augmentation therapy compared with 94 (66.2%) with PI*ZZ (p<0.001).ConclusionsThere is a high prevalence of PI*SZ in Spain. Patients with the PI*SZ genotype were older at symptom onset and diagnosis and had less severe lung disease compared with PI*ZZ. The prevalence of asthma was higher in PI*SZ, and up to 15% of PI*SZ patients received augmentation therapy.

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“…In any case, family screening should be carried out in these cases, to detect severe cases amongst younger relatives. Fortunately, current technologies facilitate these diagnostic procedures in the population [ 31 , 32 ].…”

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Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy

Lόpez-Campos

Hernández

Eraso

2020

JCM

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Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field.

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Diagnostic Performance of a Lateral Flow Assay for the Detection of Alpha-1-Antitrypsin Deficiency

Cited by 3 publications

References 8 publications

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

Demographic and clinical characteristics of patients with α₁-antitrypsin deficiency genotypes PIZZ and PISZ in the Spanish registry of EARCO

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy

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Diagnostic Performance of a Lateral Flow Assay for the Detection of Alpha-1-Antitrypsin Deficiency

Cited by 3 publications

References 8 publications

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

Demographic and clinical characteristics of patients with α1-antitrypsin deficiency genotypes PI*ZZ and PI*SZ in the Spanish registry of EARCO

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy

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Demographic and clinical characteristics of patients with α₁-antitrypsin deficiency genotypes PIZZ and PISZ in the Spanish registry of EARCO