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

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

doi:10.1016/j.arbr.2019.03.025

Cited by 11 publications

(9 citation statements)

References 32 publications

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“…In clinical practice, lung emphysema and chronic bronchitis are the most common clinical phenotypes of COPD associated with PiZZ deficiency [4]. Environmental factors, particularly cigarette smoke, greatly increase the risk of COPD development [2], and while the onset of respiratory disease in smokers occurs in the third or fourth decades of life, in nonsmokers the onset can be delayed to the fifth or sixth decades, and even some nonsmokers may have a normal life span without developing COPD or other diseases associated with AAT deficiency [5][6][7][8][9]. This striking variability of clinical expression suggests that in a number of cases AAT deficiency alone is not enough to induce COPD, and that, in addition to smoking and other environmental pollutants, genetic modifiers not yet definitively identified likely influence this clinical variability [10][11][12].…”

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confidence: 99%

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

et al. 2020

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The percentage of α1-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies. We aimed to estimate the prevalence of PiZZ in COPD patients from 20 European countries with available data, according to the number of PiZZ and COPD individuals in each country.A systematic review was conducted to select European countries with reliable data on the prevalence of PiZZ and COPD. We created a database with the following data: 1) total population and population aged ≥40 years according to the Eurostat database; 2) number and 95% CI of PiZZ patients aged ≥40 years; 3) application of a conversion factor of genetic penetrance of 60%; 4) number of COPD individuals, with 95% CI, aged ≥40 years; and 5) calculation of the PiZZ/COPD ratio. Finally, results were presented using an Inverse Distance Weighted Interpolation map.We found 36 298 (95% CI 23 643–56 594) PiZZ individuals at high risk and 30 849 709 (95% CI 21 411 293–40 344 496) COPD patients, with a PiZZ/COPD ratio of 0.12% (range 0.08–0.24%), and a prevalence of 1 out of 408 in Northern, 1 out of 944 in Western, 1 out of 1051 in Central, 1 out of 711 in Southern, and 1 out of 1274 in Eastern Europe.These data may be useful to plan strategies for future research and diagnosis, and to rationalise the available therapeutic resources.

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confidence: 99%

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

et al. 2020

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“…These inclusions are associated with neonatal hepatitis, cirrhosis and hepatocellular carcinoma [7]. In addition, lower concentrations of circulating AAT predispose to early onset panlobular emphysema in individuals with smoking history [8][9][10].…”

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Association between circulating alpha-1 antitrypsin polymers and lung and liver disease

et al. 2021

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Background Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. Method This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. Results A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). Conclusions Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.

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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.…”

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

Cited by 11 publications

References 32 publications

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

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

Association between circulating alpha-1 antitrypsin polymers and lung and liver disease

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

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

Cited by 11 publications

References 32 publications

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

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

Association between circulating alpha-1 antitrypsin polymers and lung and liver disease

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

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

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