Prevalence of α1-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Blanco, Ignacio; Diego, I.; Bueno, Patrícia; Pérez-Holanda, S.; Maldonado, Francisco Casas; Miravitlles, Marc

doi:10.1183/16000617.0014-2020

Cited by 33 publications

(25 citation statements)

References 31 publications

(35 reference statements)

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“…We observed a large increase in AAT determinations during the study period with a total of 84 (2.4%) individuals being diagnosed with severe deficiency. Considering that the prevalence of severe AATD (specifically PI*ZZ) among the general population in Spain is only 0.03% 23 and among COPD patients in Europe it is 0.12%, 24 a detection rate of 2.4% for severe deficiency can be considered a good diagnostic yield. Moreover, more than half (57.6%) of the individuals tested carried an intermediate deficiency, which is highly relevant for the individual in order to prevent disease progression and to initiate family screening for early detection of affected relatives.…”

Section: Discussionmentioning

confidence: 99%

Trends in Diagnosis of Alpha-1 Antitrypsin Deficiency Between 2015 and 2019 in a Reference Laboratory

Belmonte

Núñez

Barrecheguren

et al. 2020

COPD

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Background: Alpha-1 antitrypsin deficiency (AATD) remains largely underdiagnosed despite recommendations of healthcare institutions and programmes designed to increase awareness. The objective was to analyse the trends in AATD diagnosis during the last 5 years in a Spanish AATD reference laboratory. Methods: This was a retrospective revision of all alpha-1 antitrypsin (AAT) determinations undertaken in our laboratory from 2015 to 2019. We analysed the number of AAT determinations performed and described the characteristics of the individuals tested, as well as the medical specialties and the reasons for requesting AAT determination. Results: A total of 3507 determinations were performed, of which 5.5% corresponded to children. A significant increase in the number of AAT determinations was observed from 349 in 2015 to 872 in 2019. Among the samples, 57.6% carried an intermediate AATD (50-119 mg/dL) and 2.4% severe deficiency (<50 mg/dL). The most frequent phenotype in severe AATD individuals was PI*ZZ (78.5%), and aminotransferase levels were above normal in around 43% of children and 30% of adults. Respiratory specialists requested the highest number of AAT determinations (31.5%) followed by digestive diseases and internal medicine (27.5%) and primary care physicians (19.7%). The main reason for AAT determination in severe AATD adults was chronic obstructive pulmonary disease (41.7%), but reasons for requesting AAT determination were not reported in up to 41.7% of adults and 58.3% of children. Conclusion: There is an increase in the frequency of AATD testing despite the rate of AAT determination remaining low. Awareness about AAT is probably increasing, but the reason for testing is not always clear.

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Section: Discussionmentioning

confidence: 99%

Trends in Diagnosis of Alpha-1 Antitrypsin Deficiency Between 2015 and 2019 in a Reference Laboratory

Belmonte

Núñez

Barrecheguren

et al. 2020

COPD

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“…A recent epidemiological study reported that the prevalence of Pi*ZZ/prevalence of COPD ratio in Europe was 0.12% (0.08-0.24%), differences being wide among the countries. 21 Numbers may be even higher in other countries; in Argentina, for example, the prevalence of AATD (Pi*ZZ or Pi*SZ) among COPD patients > 40 years of age was found to be 0.83%. 22 …”

Section: Epidemiologymentioning

confidence: 95%

“…Um estudo epidemiológico recente relatou que a relação prevalência de Pi*ZZ/prevalência de DPOC na Europa foi de 0,12% (0,08-0,24%), sendo as diferenças amplas entre os países. (21) Os números podem ser ainda maiores em outros países; na Argentina, por exemplo, constatou-se uma prevalência de DAAT (Pi*ZZ ou Pi*SZ) de 0,83% entre pacientes com DPOC e idade > 40 anos. (22) Em razão da ausência de estudos específicos, pouco se sabe sobre a epidemiologia dos alelos "raros" e "nulos" da DAAT, (7) que podem ser mais prevalentes do que se supunha anteriormente.…”

Section: Genéticaunclassified

“…Embora faltem dados epidemiológicos sobre a prevalência de DAAT na população geral brasileira, (24) um estudo transversal envolvendo 926 pacientes com DPOC de cinco diferentes regiões do Brasil encontrou uma prevalência geral de 2,8% para DAAT e de 0,8% para o genótipo Pi*ZZ. (16) Esses números se alinham às estimativas de que a DAAT grave seja responsável por 0,1% a 1% dos casos de DPOC (21,22) e reforçam a necessidade de vigilância e aumento da triagem da DAAT na população brasileira com DPOC. (16)…”

Section: Genéticaunclassified

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Update on and future perspectives for the diagnosis of alpha-1 antitrypsin deficiency in Brazil

et al. 2021

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A deficiência de alfa-1 antitripsina (DAAT) é um distúrbio genético raro causado por uma mutação no gene SERPINA1, que codifica o inibidor de protease alfa-1 antitripsina (AAT).A DAAT predispõe os indivíduos a DPOC e doença hepática. O diagnóstico precoce é essencial para a implementação de medidas preventivas e para limitar a carga da doença. Embora diretrizes nacionais e internacionais para o diagnóstico e manejo da DAAT estejam disponíveis há 20 anos, mais de 85% dos casos não são diagnosticados e, portanto, não são tratados. No Brasil, os motivos para o subdiagnóstico da DAAT incluem o desconhecimento dos médicos sobre a condição, a diversidade racial da população, o fato de os níveis séricos de AAT serem avaliados em um número limitado de indivíduos e a falta de ferramentas diagnósticas convenientes. O diagnóstico da DAAT baseia-se em resultados de exames laboratoriais. A abordagem diagnóstica padrão envolve a avaliação dos níveis séricos de AAT, seguida de fenotipagem, genotipagem, sequenciamento gênico ou suas combinações para detecção da mutação específica. Nos últimos 10 anos, novas técnicas foram desenvolvidas, oferecendo uma alternativa rápida, minimamente invasiva e confiável aos métodos tradicionais de teste. Um desses testes disponíveis no Brasil é o teste de genotipagem A1AT, que analisa simultaneamente as 14 mutações mais prevalentes da DAAT usando DNA extraído de swab bucal ou de sangue em papelfiltro. Esses avanços podem contribuir para a superação do problema do subdiagnóstico no Brasil e em outros países, bem como podem aumentar a taxa de detecção da DAAT e, portanto, mitigar os malefícios do diagnóstico tardio.Descritores: Deficiência de alfa 1-antitripsina/diagnóstico; Deficiência de alfa 1-antitripsina/ genética; Técnicas de genotipagem.

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“…An estimated 3.4 million people worldwide are affected; however, under diagnosis means many individuals remain undetected so this number is likely to be higher, highlighting the need for screening programmes in at risk individuals. 6,7 There are over 120 reported mutations in this gene, with the most common being the S and Z mutations, which affect 1.4 million and 250,000 people worldwide, respectively. 8 Both mutations result in misfolding of the protein, with the S variant resulting in a proportion of the AAT protein (~40%) being retained within hepatocytes, which reduces plasma levels but may not affect susceptibility to either liver or lung disease.…”

Section: Introductionmentioning

confidence: 99%

Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency

Belchamber¹,

Walker²,

Stockley³

et al. 2020

COPD

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Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterised by low circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor. The most common deficiency variants are the S and Z mutations, which cause the accumulation of misfolded AAT in hepatocytes resulting in endoplasmic reticular stress and insufficient release of AAT into the circulation (<11μmol/L). This leads to liver disease, as well as an increased risk of emphysema due to unopposed proteolytic activity of neutrophil-derived serine proteinases in the lungs. AATD has been traditionally viewed as an inflammatory disorder caused directly by a proteinase-antiproteinase imbalance in the lung, but increasing evidence suggests that low AAT levels may affect other cellular functions. Recently, AAT polymers have been identified in both monocytes and macrophages from AATD patients and evidence is building that these cells may also play a role in the development of AATD lung disease. Alveolar macrophages are phagocytic cells that are important in the lung immune response but are also implicated in driving inflammation. This review explores the potential implications of monocyte and macrophage involvement in non-liver AAT synthesis and the pathophysiology of AATD lung disease.

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Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Cited by 33 publications

References 31 publications

<p>Trends in Diagnosis of Alpha-1 Antitrypsin Deficiency Between 2015 and 2019 in a Reference Laboratory</p>

<p>Trends in Diagnosis of Alpha-1 Antitrypsin Deficiency Between 2015 and 2019 in a Reference Laboratory</p>

Update on and future perspectives for the diagnosis of alpha-1 antitrypsin deficiency in Brazil

<p>Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency</p>

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