scholarly journals Case-finding for alpha1-antitrypsin deficiency in Kazakh patients with COPD

2017 ◽  
Vol 12 ◽  
Author(s):  
Ilaria Ferrarotti ◽  
Ardak Zhumagaliyeva ◽  
Stefania Ottaviani ◽  
Timm Greulich ◽  
Marina Gorrini ◽  
...  
Keyword(s):  
Large Population ◽  
General Concept ◽  
Dried Blood Spot ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Care Givers ◽  
Kazakh Population ◽  
Antitrypsin Deficiency ◽  
Alpha1 Antitrypsin ◽  
Blood Spot

Background: Alpha-1-antitrypsin deficiency (AATD) is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to screen for AATD in Kazakh patients with COPD using dried blood spot specimens. Methods: The alpha1-antitrypsin (AAT) concentration was determined by nephelometry, PCR was used to detect PiS and PiZ alleles; and isoelectric focusing was used to confirm questionable genotype results and detect rare AAT variants. Results: To this aim, 187 Kazakh subjects with COPD were recruited. Blood samples were collected as dried blood spot. Genotyping of 187 samples revealed 3 (1.6%) PI*MZ and 1 (0.53%) PI*MS, Phenotyping identified also two sample (1.1%) with phenotype PiMI. Allelic frequencies of pathological mutations Z, S and I resulted 0.8%, 0.3%, 0.5%, respectively, in COPD Kazakh population. Conclusions: This study proved that AATD is present in the Kazakh population. These results support the general concept of targeted screening for AAT deficiency in countries like Kazakhstan, with a large population of COPD patients and low awareness among care-givers about this genetic condition.

scholarly journals Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches

2021 ◽  
Vol 22 (3) ◽  
pp. 1065
Author(s):  
Simona Viglio ◽  
Elisabeth G. Bak ◽  
Iris G. M. Schouten ◽  
Paolo Iadarola ◽  
Jan Stolk
Keyword(s):  
Serine Proteases ◽  
Lung Parenchyma ◽  
New Drugs ◽  
Chronic Obstructive ◽  
Augmentation Therapy ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Antitrypsin Deficiency ◽  
Novel Biomarkers ◽  
Alpha1 Antitrypsin

As a known genetic cause of chronic obstructive pulmonary disease (COPD), alpha1-antitrypsin deficiency (AATD) can cause severe respiratory problems at a relatively young age. These problems are caused by decreased or absent levels of alpha1-antitrypsin (AAT), an antiprotease which is primarily functional in the respiratory system. If the levels of AAT fall below the protective threshold of 11 µM, the neutrophil-derived serine proteases neutrophil elastase (NE) and proteinase 3 (PR3), which are targets of AAT, are not sufficiently inhibited, resulting in excessive degradation of the lung parenchyma, increased inflammation, and increased susceptibility to infections. Because other therapies are still in the early phases of development, the only therapy currently available for AATD is AAT augmentation therapy. The controversy surrounding AAT augmentation therapy concerns its efficiency, as protection of lung function decline is not demonstrated, despite the treatment’s proven significant effect on lung density change in the long term. In this review article, novel biomarkers of NE and PR3 activity and their use to assess the efficacy of AAT augmentation therapy are discussed. Furthermore, a series of seven synthetic NE and PR3 inhibitors that can be used to evaluate the specificity of the novel biomarkers, and with potential as new drugs, are discussed.

scholarly journals The prevalence of diagnosed α1-antitrypsin deficiency and its comorbidities: results from a large population-based database

2016 ◽  
Vol 49 (1) ◽  
pp. 1600154 ◽  
Author(s):  
Timm Greulich ◽  
Christoph Nell ◽  
David Hohmann ◽  
Marco Grebe ◽  
Sabina Janciauskiene ◽  
...  
Keyword(s):  
Large Population ◽  
Age Groups ◽  
Clinical Manifestations ◽  
Healthcare Utilisation ◽  
International Classification Of Diseases ◽  
Population Based ◽  
Chronic Obstructive ◽  
Healthcare Database ◽  
Obstructive Pulmonary Disease ◽  
Antitrypsin Deficiency

α1-Antitrypsin deficiency (AATD) is a genetically determined disorder that is associated with different clinical manifestations. We aimed to assess the prevalence of diagnosed AATD and its comorbidities using a large healthcare database.In this retrospective longitudinal observational study, we analysed data from 4 million insurants. Using International Classification of Diseases revision 10 (ICD-10) codes, we assessed the prevalence, comorbidities and healthcare utilisation of AATD patients (E88.0 repeatedly coded) relative to non-AATD patients with chronic obstructive pulmonary disease (COPD), emphysema or asthma.In our study population, we identified 673 AATD patients (590 aged ≥30 years), corresponding to a prevalence of 23.73 per 100 000 in all age groups and 29.36 per 100 000 in those ≥30 years. Based on the number of AATD cases detected in the sample size (673 out of 2 836 585), we extrapolated that there were 19 162 AATD cases in Germany during the years studied. AATD patients had a higher prevalence of arterial hypertension, chronic kidney disease and diabetes relative to non-AATD asthma or emphysema patients. When compared to non-AATD COPD patients, AATD patients had significantly more consultations and more frequent and longer hospitalisations.Our data strengthen the assumption that AATD is associated with a variety of other diseases. Healthcare utilisation appears to be higher among AATD patients as compared to patients with non-AATD-related obstructive lung diseases.

scholarly journals Imaging in alpha-1 antitrypsin deficiency: a window into the disease

2021 ◽  
Vol 12_suppl ◽  
pp. 204062232110245
Author(s):  
Yuh-Chin Tony Huang ◽  
Marion Wencker ◽  
Bastiaan Driehuys
Keyword(s):  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Essential Information ◽  
Plain Chest Radiograph ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
History Of ◽  
Detailed Assessment ◽  
Alpha 1 Antitrypsin ◽  
Magnetic Resonance Imaging Mri

Imaging modalities such as plain chest radiograph and computed tomography (CT) are important tools in the assessment of patients with chronic obstructive pulmonary disease (COPD) of any etiology. These methods facilitate differential diagnoses and the assessment of individual lung pathologies, such as the presence of emphysema, bullae, or fibrosis. However, as emphysema is the core pathological consequence in the lungs of patients with alpha-1 antitrypsin deficiency (AATD), and because AATD is associated with the development of other lung pathologies such as bronchiectasis, there is a greater need for patients with AATD than those with non-AATD-related COPD to undergo more detailed assessment using CT. In the field of AATD, CT provides essential information regarding the presence, distribution, and morphology of emphysema. In addition, it offers the option to quantify the extent of emphysema. These data have implications for treatment decisions such as initiation of alpha-1 antitrypsin (AAT) therapy, or suitability for surgical or endoscopic interventions for reducing lung volume. Furthermore, CT has provided vital insight regarding the natural history of emphysema progression in AATD, and CT densitometry has underpinned research into the efficacy of AAT therapy. Moving forward, hyperpolarized xenon gas (129Xe) lung magnetic resonance imaging (MRI) is emerging as a promising complement to CT by adding comprehensive measures of regional lung function. It also avoids the main disadvantage of CT: the associated radiation. This chapter provides an overview of technological aspects of imaging in AATD, as well as its role in the management of patients and clinical research. In addition, perspectives on the future potential role of lung MRI in AATD are outlined.

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