Serum Levels of Alpha1-antitrypsin and Their Relationship With COPD in the General Spanish Population

Janciauskiene, Sabina; DeLuca, David S.; Barrecheguren, Miriam; Welte, Tobias; Miravitlles, Marc; Ancochea, Julio; Badiola, Carlos; Sánchez, Guadalupe; Durán, Enric; Río, Francisco García; Muñoz, Luis; Sobradillo, V.; Soriano, Joan B.; Borderías, Luis; Martínez, Jorge L.; Montemayor, Teodoro; Piñeiro, Luis; Serra, Joan; Soler-Cataluña, Juan José; Torres, Antoni; Viejo, José Luís

doi:10.1016/j.arbres.2019.03.001

Cited by 24 publications

(8 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…31 In addition, AAT levels were lower in ACO and EE. Higher AAT and CRP levels have shown to be associated with an increased risk of COPD in the general population without AAT deficiency; 32,33 however, the reduced levels of AAT observed in ACO patients have not been described previously. 34,35 Eosinophils are end-stage cells produced under the influence of macrophage colony-stimulating factor, interleukin (IL)-3 and the late differentiation factor IL-5.…”

Section: Discussionmentioning

confidence: 91%

<p>Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease</p>

Núñez¹,

Marras²,

Harlander³

et al. 2020

COPD

Self Cite

View full text Add to dashboard Cite

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations. Methods: Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators. Results: A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators. Conclusion: Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

show abstract

Section: Discussionmentioning

confidence: 91%

<p>Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease</p>

Núñez¹,

Marras²,

Harlander³

et al. 2020

COPD

Self Cite

View full text Add to dashboard Cite

show abstract

“…(6,7,25) Além do mais, como a DPOC associa-se a inflamação sistêmica, os níveis de AAT podem estar elevados em pacientes com DPOC em comparação a controles pareados por idade, aumentando assim os desafios de identificar possíveis heterozigotos entre a população com DPOC. (43,44) Embora a presença de inflamação geralmente não influencie o diagnóstico da DAAT em homozigotos Pi*ZZ, para não deixar de detectar portadores ou outros pacientes com deficiência, pode ser útil adotar uma abordagem mais geral, medindo os níveis de proteína C reativa e AAT ao mesmo tempo. Um nível normal de proteína C reativa confirma que os níveis de AAT estão verdadeiramente, e não falsamente, elevados.…”

Section: Métodos Diagnósticos Padrãounclassified

“… 6 , 7 , 25 Moreover, because COPD is associated with systemic inflammation, AAT levels can be elevated in COPD patients when compared with age-matched controls, thus increasing the challenges of identifying possible heterozygotes among the COPD population. 43 , 44 Although the presence of inflammation does not generally influence a diagnosis of AATD in Pi*ZZ homozygotes, in order not to miss carriers or other patients with a deficiency, it may be useful to take a more general approach by measuring CRP and AAT levels at the same time. A normal level of CRP confirms that AAT levels are true and not falsely elevated.…”

Section: Laboratory Diagnosismentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…Although there may be extreme values in the distributions, there is little information on very young or very old cases. Although cases in children requiring augmentation therapy have been described anecdotally [28], being young is not normally an issue from a clinical perspective, since by the time emphysema develops, patients are already young adults [29,30]. The issue comes with elderly cases.…”

Section: Age Limitsmentioning

confidence: 99%

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

Lόpez-Campos

Hernández

Eraso

2020

JCM

View full text Add to dashboard Cite

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.

show abstract

Serum Levels of Alpha1-antitrypsin and Their Relationship With COPD in the General Spanish Population

Cited by 24 publications

References 32 publications

<p>Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease</p>

<p>Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease</p>

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

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

Contact Info

Product

Resources

About