1,721,027 research outputs found
COPD: no gene left unturned
No full textChronic obstructive pulmonary disease (COPD) is defined as a disease causing an airflow limitation that is not fully reversible. COPD is phenotypically complex and characterized by small-airway disease and/or emphysema that result from the interaction between host genetic susceptibility and environmental exposures
Update on α1-antitrypsin deficiency
No full textα1-Antitrypsin deficiency (AATD) is an inherited metabolic disorder in which mutations in the coding sequence of the SERPINA1 gene prevent secretion of α1-antitrypsin (α1-AT) and cause predisposition to pulmonary and liver diseases. The heterogeneity of clinical manifestations in AATD is related to the complexity of biological function of α1-AT. The role of smoking is crucial in the natural history of lung damage progression in severe AATD individuals, even if it also partly explains the heterogeneity in lung disease. Lung damage progression in AATD can also be related to body mass index, exacerbation rate, sex, environmental exposure and specific mutations of SERPINA1. Recent randomised controlled trials, together with previous observational work, have provided compelling evidence for the importance of early detection and intervention in order to enable patients to receive appropriate treatment and preserve functional lung tissue
Inherited alpha1-antitrypsin deficiency: Is the level the key message?
No full textFifty-one years ago, two scientists from the Malmö University, Carl Bertil Laurell and Sten Eriksson, first reported five individuals affected by inherited alpha1-antitrypsin (α1 -AT) deficiency. Of particular interest, this original nucleus of described patients, already included the spectrum of clinical phenotypic variability associated with this genetic disorder: absence of any respiratory disease, juvenile or late pulmonary emphysema, disseminated bronchiectasis. Since then, knowledge on the related epidemiology, pathophysiology, pathogenesis, clinical course, and treatment has dramatically improved, as evidenced by the authoritative published review articles. Still, there are a number of open questions awaiting on answer
Advances in Identifying Urine/Serum Biomarkers in Alpha-1 Antitrypsin Deficiency for More Personalized Future Treatment Strategies
No full textAlpha1-antitrypsin deficiency (AATD) is a genetic disorder characterized by reduced serum levels of alpha1-antitrypsin (AAT) and increased risk for developing both early-onset lung emphysema and chronic liver disease. Laboratory diagnosis of AATD is not just a matter of degree, although the AAT serum level is the most important determinant for risk of lung damage. While being a single-gene disease, the clinical phenotype of AATD is heterogeneous. The current standard of care for patients affected by AATD-associated pulmonary emphysema is replacement therapy with weekly i.v. infusions of pooled human purified plasma AAT. Although no treatment for liver disease caused by deposition of abnormal AAT in hepatocytes is available, innovative treatments for this condition are on the horizon. This article aims to provide a critical review of the methodological steps that have marked progress in the detection of indicators described in the literature as being “clinically significant” biomarkers of the disease. The development and routine use of specific biomarkers would help both in identifying which patients and when they are eligible for treatment as well as providing additional parameters for monitoring the disease
Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma
No full textBACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD.OBJECTIVES: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation.METHODS: We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system.RESULTS: The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (p = 0.014 and p = 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution.CONCLUSIONS: In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping
Identification and characterisation of seven novel SERPINA1 null mutations
No full textBackground- Alpha-1 antitrypsin (AAT) is a serine protease inhibitor, encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD) which is associated with a substantially increased risk of lung and liver disease. A group of rare mutations causing AATD, termed Null, are characterised by a complete absence of AAT in the plasma, that confer a particularly high risk of emphysema.
Objectives- Here we reported the novel Null AAT mutations that we discovered during the Italian and Irish targeted detection programs of AATD.
Methods-We performed the determination of AAT serum levels by a rate immune nephelometric method or by immune turbidimetry. The phenotype was determined by isoelectric focusing analysis.DNA was isolated from whole peripheral blood or dried blood spot (DBS) samples using a commercial extraction kit. The new mutations were identified by sequencing all coding exons of the SERPINA1 gene.
Results-We identified seven previously unidentified SERPINA1 Null mutations. Three are nonsense mutations, the others are frameshift mutations caused by deletion of one or two nucleotides. We also performed familial screening. Analysis of the clinical characteristics revealed the recurrence of lung symptoms and lung diseases in M/Null subjects, over 45 years-old, irrespective of their smoking habit.
Conclusions We added seven more mutations to the list of SERPINA1 Null alleles. Moreover, we underlined that the laboratory diagnosis of AATD is not just a matter of degree, because the precise determination of the deficiency and Null alleles carried by an AATD individual may help to evaluate the risk for the lung disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
alpha1-antitrypsin level and pheno/genotypes
No full textThe authors comment on a few aspects regarding the interpretation of the reference values given in a previously pubblished paper
1. (Bornhorst JA, Greene DN, Ashwood ER, Grenache DG. A1-antitrypsin phrnotypes and associated serum protein concentration in a large clinical population. Chest 2013; 143:1000-1008.
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