scholarly journals Small airways dysfunction is associated to Alpha-1 Antitrypsin Deficiency in patients with asthma

2019 ◽  
Author(s):  
Marina Aiello ◽  
Marianna Ghirardini ◽  
Roberta Pisi ◽  
Ilaria Ferrarotti ◽  
Giuseppina Bertorelli ◽  
...  
Keyword(s):  
Lung Function ◽  
Genetic Disorder ◽  
University Hospital ◽  
Small Airways ◽  
Air Trapping ◽  
Asthmatic Patients ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Few Data

Abstract Background Alpha-1 Antitrypsin Deficiency (AATD) is a hereditary genetic disorder involving lungs in adults, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT). Several reports indicate that asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with intermediate AATD. The aim of the study is to evaluate lung function in asthmatic outpatients with AATD vs. asthmatic subjects without AATD.Methods We enrolled 57 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. We submitted to genetic analysis the asthmatic outpatients with a serum AAT concentration <113 mg/dL and those with relatives affected by AATD. Subsequently, the study population was split into AATD and not AATD subjects. We assessed lung function through a flow-sensing spirometer and the small airways parameters through an impulse oscillometry system.Results The values of FVC (% predicted) and of the RV/TLC (%) ratio were respectively lower and higher in patients with AATD vs. patients without AATD, showing a significantly greater air trapping (p = 0.014 and p = 0.017 respectively). Moreover, patients with AATD in comparison to patients without AATD showed lower FEV3 (% predicted) and FEV6 (L) values. A significant and positive correlation (p=0.041; r=0.894) occurred between the RV/TLC ratio and the years of smoking in the group of asthmatic patients with AATD.Conclusions AATD predisposes asthmatic heterozygote patients with PI*MZ, PI*MS and intermediate levels of AAT to small airways dysfunction and to increased values of pulmonary air trapping.

Air trapping is associated with heterozygosity for Alpha-1  Antitrypsin mutations in patients with asthma

2020 ◽  
Author(s):  
Marina Aiello ◽  
Ghirardini Marianna ◽  
Pisi Roberta ◽  
Ferrarotti Ilaria ◽  
Bertorelli Giuseppina ◽  
...  
Keyword(s):  
Lung Function ◽  
Serum Concentration ◽  
Genetic Disorder ◽  
University Hospital ◽  
Small Airways ◽  
Air Trapping ◽  
Asthmatic Patients ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Few Data

Abstract Background: Alpha-1 Antitrypsin Deficiency (AATD) is a hereditary genetic disorder involving lungs in adults, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT). Several reports indicate that asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. The aim of the study is to evaluate lung function in asthmatic outpatients with AATD vs. asthmatic subjects without AATD. 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 AATD and non-AATD subjects. All the AATD patients had a heterozygous genotype, except one (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airways parameters through an impulse oscillometry system.Results: The values of FVC (% predicted) and of the RV/TLC (%) ratio were respectively lower and higher in patients with AATD vs. patients without AATD, showing a significantly greater air trapping (p = 0.014 and p = 0.017 respectively). Moreover, patients with AATD in comparison to patients without AATD showed lower FEV3 (% predicted) and FEV6 (L) spirometric values, reflecting a smaller airways contribution.Conclusions: AATD in asthmatic heterozygote patients with PI*MZ and PI*MS genotypes was associated with small airways dysfunction and with lung air trapping.

scholarly journals Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma

Respiration ◽  
2021 ◽  
pp. 1-10
Author(s):  
Marina Aiello ◽  
Marianna Ghirardini ◽  
Laura Marchi ◽  
Annalisa Frizzelli ◽  
Roberta Pisi ◽  
...  
Keyword(s):  
Lung Function ◽  
Serum Concentration ◽  
Forced Expiratory Volume ◽  
Small Airway ◽  
University Hospital ◽  
Air Trapping ◽  
Asthmatic Patients ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Few Data

<b><i>Background:</i></b> 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. <b><i>Objectives:</i></b> The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the <i>SERPINA1</i> gene coding for AAT versus asthmatic subjects without mutation. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 (<i>p =</i> 0.014 and <i>p =</i> 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. <b><i>Conclusions:</i></b> In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

Small airway evaluation in three subjects with alpha-1 antitrypsin deficiency without diagnosed lung disease

2021 ◽  
Vol 14 (3) ◽  
pp. e239146
Author(s):  
Thais Ferrari da Cruz ◽  
Rogério Rufino ◽  
Agnaldo Lopes ◽  
Cláudia Henrique Costa
Keyword(s):  
Pulmonary Function ◽  
Pulmonary Function Tests ◽  
Genetic Disorder ◽  
Early Investigation ◽  
Small Airways ◽  
Nitrogen Washout ◽  
Function Tests ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

We describe three cases of female subjects (aged 16, 44 and 41 years) with no respiratory symptoms, who have alpha-1 antitripsyn mutation (PiSZ, PiZZ and PiZZ) and who performed traditional pulmonary function tests and the single breath nitrogen washout test. They still did not have chronic obstructive pulmonary disease (COPD) or any identifiable change in traditional pulmonary function tests but already have change in nitrogen washout tests. Alpha-1 antitrypsin deficiency is a genetic disorder associated with early-onset COPD. There is evidence that although patients who have well-preserved FEV1 may already have signs of emphysema associated with symptoms. Therefore, the nitrogen washout test is considered to have more sensitive outcomes than other pulmonary function tests for early investigation of small airways disease and could allow the monitoring pulmonary function and evaluating of therapeutic decision.

Nephrotic syndrome secondary to alpha-1 antitrypsin deficiency

2021 ◽  
Vol 14 (3) ◽  
pp. e240288
Author(s):  
Gabriela F Santos ◽  
Paul Ellis ◽  
Daniela Farrugia ◽  
Alice M Turner
Keyword(s):  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Clinical Investigation ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Protective Role ◽  
Caucasian Woman ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

We report a 64-year-old caucasian woman diagnosed with membranous nephropathy secondary to alpha-1 antitrypsin deficiency (AATD). AATD is a rare autosomal codominant genetic disorder. Its clinical manifestations are mostly observed in the lungs, with early-onset emphysema. Nephropathy due to AATD is still very rare and only a few cohort studies have been reported. It has been recognised that alpha-1 antitrypsin has a protective role in the kidneys which enhances the possibility of development of kidney failure, such as nephrotic syndrome, in cases of AATD. Further clinical investigation is needed to understand the relationship between the development of nephropathy, namely membranous nephropathy, and AATD.

scholarly journals Lung function and CT lung densitometry in 37- to 39-year-old individuals with alpha-1-antitrypsin deficiency

2018 ◽  
Vol Volume 13 ◽  
pp. 3689-3698 ◽  
Author(s):  
Behrouz Mostafavi ◽  
Sandra Diaz ◽  
Eeva Piitulainen ◽  
Berend Stoel ◽  
Per Wollmer ◽  
...  
Keyword(s):  
Lung Function ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Lung Densitometry

Alpha-1-antitrypsin deficiency: diagnosis and treatment (literature review)

2021 ◽  
pp. 12-24
Author(s):  
Е.А. Ларшина ◽  
Н.В. Милованова ◽  
Е.А. Каменец
Keyword(s):  
Liver Disease ◽  
Genetic Disorder ◽  
New Drugs ◽  
Chronic Obstructive ◽  
Diagnosis Delay ◽  
Loss Of Function ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
A1at Deficiency ◽  
Alpha 1 Antitrypsin

Недостаточность альфа-1-антитрипсина - наследственное заболевание, характеризующееся низким уровнем белка альфа-1-антитрипсина (A1AT) в крови. В основном дефицит A1AT проявляется в виде хронической обструктивной болезни легких (ХОБЛ), эмфиземы, а также поражения печени и сосудов. А1АТ является главным ингибитором сериновых протеаз в крови человека. Недостаточность А1АТ обусловлена мутациями в гене SERPINA1. Наиболее распространенными аллельными вариантами в гене SERPINA1 являются S (p.Glu288Val) и Z (р.Glu366Lys), однако в клинической практике большинство случаев тяжелого дефицита А1АТ связаны с генотипом PIZZ. У пациентов с PIZZ патология легких представляет собой фенотип «потери функции», так как дефицит A1AT приводит к ускоренному разрушению паренхимы легких, приводящему к эмфиземе. При Z-мутации 85% синтезированного белка блокируется в гепатоцитах из-за неправильного сворачивания и полимеризации. Накопление полимеризованного белка в эндоплазматической сети гепатоцитов в свою очередь приводит к хроническим заболеваниям печени у некоторых пациентов: циррозу и злокачественным новообразованиям печени. Дефицит А1АТ является довольно распространенным заболеванием, но выявляется лишь незначительная часть лиц с данной патологией. Недостаточность А1АТ зачастую ошибочно диагностируется как ХОБЛ, бронхиальная астма или криптогенное заболевание печени. Задержка в установлении диагноза составляет обычно более 5 лет (в среднем около 8 лет) что, как правило, связано с плохой осведомленностью врачей, недооценкой его распространенности и вариабельностью клинических проявлений. В настоящее время для лечения дефицита А1АТ с легочными проявлениями возможно применение аугментационной терапии, основанной на внутривенном введении очищенного человеческого А1АТ. Также активно ведется поиск новых препаратов, способных улучшить прогноз у пациентов с патологией печени. Современные подходы в лечении дефицита А1АТ, сосредоточенные на генной терапии, становятся перспективным направлением в лечении как легочной, так и печеночной патологии при дефиците А1АТ. Alpha-1 antitrypsin deficiency is a genetic disorder characterized by low level of alfa-1-antitripsin protein (A1AT) in the blood. Usually, A1AT deficiency results in chronic obstructive pulmonary disease (COPD), emphysemas, liver disease and vessels damaging. A1AT is the main inhibitor of serine proteases in human blood. A1AT deficiency is caused by mutations in the gene SERPINA1. The most common SERPINA1 allelic variants are S (p.Glu288Val) and Z (p.Glu366Lys). However, the most of documented severe cases of A1AD are associated with PIZZ genotype. PIZZ genotype patients have loss-of-function phenotype due to accelerated lung parenchyma destruction resulting in emphysema. Z mutation genotype leads to blocking of 85% synthesized protein in hepatocytes due to wrong folding and polymerization. Accumulation of the bodied protein in hepatocytes endoplasmic reticulum results in chronic liver disease, cirrhosis and other liver pathologies. A1AT deficiency is a common disorder, however, this diagnosis is established in a small part of the patients. A1AT deficiency is often misdiagnosed as COPD, asthma or сryptogenic liver disease. Usually, due to underestimating the prevalence of the disease and its unspecific symptoms, the diagnosis delay is more than 5 years (on average about 8 years). Nowadays it is possible to treat lung form of A1AT deficiency used the augmentation therapy, that bases on intravenous infusions of pure human A1AT. Also, the active development of new drugs to improve the prognosis in the patients with liver pathology is ongoing. Modern approaches of A1AT deficiency treatment, focused on gene therapy, are becoming a promising direction in the managing of both pulmonary and hepatic pathology with A1AT deficiency.

scholarly journals Relationship of CT densitometry to lung physiological parameters and health status in alpha-1 antitrypsin deficiency: initial report of a centralised database of the NIHR rare diseases translational research collaborative

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e036045
Author(s):  
Diana Crossley ◽  
James Stockley ◽  
Charlotte E Bolton ◽  
Nicholas S Hopkinson ◽  
Ravi Mahadeva ◽  
...  
Keyword(s):  
Health Status ◽  
Lung Function ◽  
Lung Disease ◽  
Clinical Features ◽  
Obstructive Lung Disease ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

ObjectivesTo establish a database network for the study of alpha-1 antitrypsin deficiency (AATD) and compare the results to CT lung density as the most direct measure of emphysema.DesignA central electronic database was established to permit the upload of anonymised patient data from remote sites. Prospectively collected CT data were recorded onto disc, anonymised, analysed at the coordinating centre and compared with the clinical features of the disease.SettingTertiary referral centres with expertise in the management of AATD focused on academic Biomedical Research Units and Wellcome Clinical Research Facilities.ParticipantsData were collected from 187 patients over 1 year from eight UK academic sites. This included patient demographics, postbronchodilator physiology, health status and CT. Analysis was undertaken at the coordinating centre in Birmingham.ResultsPatient recruitment in the 12 months reached 94% of target (set at 200) covering the whole spectrum of the disease from those with normal lung function to very severe chronic obstructive lung disease. CT scan suitable for analysis was available from 147 (79%) of the patients. CT density, analysed as the threshold for the lowest 15% of lung voxels, showed statistically significant relationships with the objective physiological parameters of lung function as determined by spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity staging (p<0.001) and carbon monoxide gas transfer (p<0.01). Density also correlated with subjective measures of quality of life (p=0.02).ConclusionsEstablishment of the network for data collection and its transfer was highly successful facilitating future collaboration for the study of this rare disease and its management. CT densitometry correlated well with the objective clinical features of the disease supporting its role as the specific marker of the associated emphysema and its severity. Correlations with subjective measures of health, however, were generally weak indicating other factors play a role.

scholarly journals Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT)

2018 ◽  
Vol Volume 13 ◽  
pp. 1001-1007 ◽  
Author(s):  
Cristina Esquinas ◽  
Sonia Serreri ◽  
Miriam Barrecheguren ◽  
Esther Rodríguez ◽  
Alexa Nuñez ◽  
...  
Keyword(s):  
Lung Function ◽  
Long Term Evolution ◽  
Term Evolution ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals Kraujo krešumo sistemos pokyčiai sergant paveldimąja plaučių emfizema

2005 ◽  
Vol 3 (1) ◽  
pp. 0-0
Author(s):  
Vytis Bajoriūnas ◽  
Romaldas Rubikas ◽  
Paulius Gradauskas ◽  
Diana Samiatina ◽  
Algirdas Vilčinskas ◽  
...  
Keyword(s):  
Pulmonary Emphysema ◽  
Spontaneous Pneumothorax ◽  
Blood Clotting ◽  
Pleural Cavity ◽  
University Hospital ◽  
The Family ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Medical University

Vytis Bajoriūnas, Romaldas Rubikas, Paulius Gradauskas, Diana Samiatina, Algirdas Vilčinskas, Leonas JasulaitisKauno medicinos universitetoTorakalinės chirurgijos klinika,Eivenių g. 2, LT-50009 KaunasEl paštas: [email protected], [email protected] Įvadas Pateikiami penkių gydytų pacientų ligos istorijų duomenys, aprašoma kraujo krešumo sistemos patologija sergant paveldima plaučių emfizema. Ligoniai ir metodai 2000–2003 metais Torakalinės chirurgijos klinikoje gydyti penki vienos giminės nariai, sirgę spontaninio pneumotorakso komplikuota plaučių emfizema. Įgimta plaučių emfizema šeimoje sirgo ir šiuo metu serga 12 žmonių. Visi ligoniai buvo operuoti. Atliktos torakotomijos, rezekuota pažeista plaučio dalis, atlikta dalinė arba visiškoji pleurektomija, drenuota pleuros ertmė. Rezultatai Pooperaciniu laikotarpiu visiems ligoniams padidėjo kraujavimas į pleuros ertmę. Netekto kraujo tūris buvo papildomas hemotransfuzija, šviežiai šaldytos plazmos infuzijomis. Dėl kraujavimo į pleuros ertmę ar susidariusio hemotorakso buvo atliktos trys retorakotomijos. Pakartotinių operacijų metu buvo rastas įvairaus dydžio hemotoraksas (600–1100 ml), difuzinis kraujavimas iš krūtinės sienos be aiškaus vieno kraujavimo židinio. Visi pacientai pasveiko. Išvada Turimi duomenys yra būdingi įgimtam alfa-1 antitripsino sintezės defektui. Reikšminiai žodžiai: plaučių emfizema, spontaninis pneumotoraksas, pooperacinės komplikacijos, antitrombinas III Malfunction of blood clotting associated with hereditary pulmonary emphysema Vytis Bajoriūnas, Romaldas Rubikas, Paulius Gradauskas, Diana Samiatina, Algirdas Vilčinskas, Leonas JasulaitisClinic of Thoracic Surgery,Kaunas University of Medicine,Eivenių str. 2, LT-50009 Kaunas, LithuaniaE-mail: [email protected], [email protected] Background / objective There were five members of one family suffering from pulmonary emphysema complicated with spontaneous pneumothorax, treated at Kaunas Medical University Hospital since 2000 till 2003. The data from the case histories of all the patients are presented and the possible reasons for blood clotting dysfunction are discussed. Patients and methods Twelve members of the family have been or still are suffering from congenital pulmonary emphysema. Five members of the family were operated on. The surgey involved thoracotomy, resection of the damaged section of a lung, partial or total pleurectomy, pleural cavity drainage. Results All the patients underwent surgery, and in all cases the postoperative intrapleural bleeding was uncommonly intensive. In three cases rethoracotomies were performed. All patients survived. Conclusion The presented data characterise congenital alpha-1-antitrypsin deficiency. Keywords: pulmonary emphysema, spontaneous pneumothorax, post-operative complications, antithrombin

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