scholarly journals European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency

2017 ◽  
Vol 50 (5) ◽  
pp. 1700610 ◽  
Author(s):  
Marc Miravitlles ◽  
Asger Dirksen ◽  
Ilaria Ferrarotti ◽  
Vladimir Koblizek ◽  
Peter Lange ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pulmonary Disease ◽  
Pulmonary Emphysema ◽  
Specific Treatment ◽  
Diagnostic Methods ◽  
European Respiratory Society ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
History Of ◽  
Never Smokers

α1-antitrypsin deficiency (AATD) is the most common hereditary disorder in adults. It is associated with an increased risk of developing pulmonary emphysema and liver disease. The pulmonary emphysema in AATD is strongly linked to smoking, but even a proportion of never-smokers develop progressive lung disease. A large proportion of individuals affected remain undiagnosed and therefore without access to appropriate care and treatment.The most recent international statement on AATD was published by the American Thoracic Society and the European Respiratory Society in 2003. Since then there has been a continuous development of novel, more accurate and less expensive genetic diagnostic methods. Furthermore, new outcome parameters have been developed and validated for use in clinical trials and a new series of observational and randomised clinical trials have provided more evidence concerning the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD.As AATD is a rare disease, it is crucial to organise national and international registries and collect information prospectively about the natural history of the disease. Management of AATD patients must be supervised by national or regional expert centres and inequalities in access to therapies across Europe should be addressed.

scholarly journals Diagnosis and treatment of pulmonarydisease in α1-antitrypsin deficiency: a statement of European Respiratory Society

2018 ◽  
Vol 28 (3) ◽  
pp. 273-295
Author(s):  
Article Editorial
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Specific Treatment ◽  
Diagnostic Methods ◽  
European Respiratory Society ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
History Of ◽  
Never Smokers ◽  
Number Of Individuals

Alfa-1-antitrypsin deficiency (AATD) is the most common hereditary disorder in adults. It is associated with an increased risk of developing pulmonary emphysema and liver disease. The lung injury in AATD is closely associated with smoking, but progressive lung disease could occur even in never-smokers. A number of individuals with AATD remain undiagnosed and therefore do not receive appropriate care and treatment. The most recent international document on AATD was the joint statement of the American Thoracic Society and the European Respiratory Society published in 2003. Thereafter, there has been a continuous development of novel, more accurate and less expensive genetic diagnostic methods. Furthermore, new outcome parameters have been developed and validated for use in clinical trials and a new series of observational and randomized clinical trials have provided more evidence concerning the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD. As AATD is a rare disease, it is important to createnational and international registries and to collect information prospectively about the natural history of the disease. Management of AATD patients must be supervised by national or regional expert centres and inequalities in access to therapies across Europe should be addressed.

Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold

2021 ◽  
pp. 2101410
Author(s):  
Alessandro N. Franciosi ◽  
Daniel Fraughen ◽  
Tomás P. Carroll ◽  
Noel G. McElvaney
Keyword(s):  
Risk Estimation ◽  
Specific Treatment ◽  
Weekly Administration ◽  
Risk Assessment Models ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
Dosing Regimens ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Protective Threshold

AATD is the only readily identifiable monogenic cause of COPD. To date the only condition-specific treatment for AATD-associated COPD is weekly administration of intravenous purified pooled human AAT (IV-AAT). Uncertainties regarding which AATD genotypes should benefit from IV-AAT persist. IV-AAT is costly and involves weekly administration of a plasma product. Much of the risk stratification has been centred around the long-accepted hypothesis of a “putative protective threshold” of 11 µM (0.57 g·L−1) in serum. This hypothesis has become central to the paradigm of AATD care, though its derivation and accuracy for defining risk of disease remain unclear.We review the literature and examine the association between the 11 µM threshold and clinical outcomes to provide context and insight into the issues surrounding this topic.We found no data which demonstrates an increased risk of COPD dependent on the 11 µM threshold. Moreover, an abundance of recent clinical data examining this threshold refutes the hypothesis. Conversely, the use of 11 µM as a treatment target in appropriate ZZ individuals is supported by clinical evidence, although more refined dosing regimens are being explored.Continued use of the 11 µM threshold as a determinant of clinical risk is questionable, perpetuates inappropriate AAT-augmentation practices, may drive increased healthcare expenditure and should not be used as an indicator for commencing treatment.Genotype represents a more proven indicator of risk, with ZZ and rare ZZ-equivalent genotypes independently associated with COPD. New and better risk assessment models are needed to provide individuals diagnosed with AATD with reliable risk estimation and optimised treatment goals.

scholarly journals Alpha-1 antitrypsin deficiency as a common treatable mechanism in chronic respiratory disorders and for conditions different from pulmonary emphysema? A commentary on the new European Respiratory Society statement

2018 ◽  
Vol 13 ◽  
Author(s):  
Stefano Aliberti ◽  
Andrea Gramegna ◽  
Marco Confalonieri ◽  
Angelo Corsico ◽  
Luca Richeldi ◽  
...  
Keyword(s):  
Lung Disease ◽  
Pulmonary Emphysema ◽  
Future Research ◽  
Common Mechanism ◽  
Main Body ◽  
New Paradigm ◽  
European Respiratory Society ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Background: The European Respiratory Society recently published an important statement reviewing available evidence on diagnosis and treatment of lung disease associated to alpha-1 antitrypsin deficiency (AATD). Several issues on this topic still remain unresolved and subject of interpretation according to different standard procedures and healthcare systems worldwide. The purpose of this commentary is to offer a critical contribution to most of these controversial issues in light of an Italian perspective for the management of this disease. Main body: The clinical spectrum of AATD lung disease might include different manifestations and the traditional paradigm of a younger emphysematous patient has been revealing insufficient. Targeting with appropriate testing only COPD patients might be considered a limited approach leading to underestimation of the real prevalence of the disease. Several reports have suggested the association between AATD and other chronic respiratory conditions, as asthma and bronchiectasis. A deeper evaluation of clinical, radiological, microbiological and functional variables is, therefore, needed in order to investigate different phenotypes in AATD patients. In addition, a new line of translational research in AATD might focus on the development of personalized therapeutic regimens taking into account the patient clinical profile and needs. Conclusions: Over the past years, AATD has been interpreted as a common mechanism of inflammatory disequilibrium and tissue damage across different conditions. Future research is gradually pointing toward this new paradigm by expanding the evidence of the role of AAT as a potent immunomodulatory and anti-inflammatory drug in conditions different from pulmonary emphysema.

scholarly journals How should the ticagrelor be used? The point after the TWILIGHT and THEMIS-PCI studies

2020 ◽  
Vol 22 (Supplement_L) ◽  
pp. L72-L76
Author(s):  
Laura Gatto ◽  
Francesco Prati
Keyword(s):  
Clinical Trials ◽  
Heart Attack ◽  
Randomized Clinical Trials ◽  
Stable Coronary Artery Disease ◽  
Diabetic Patients ◽  
Increased Risk ◽  
The Face ◽  
Risk Patients ◽  
History Of ◽  
Artery Disease

Abstract The ticagrelor represents a cornerstone of antiplatelet therapy and its use has been supported, over the years, by several clinical trials that have enrolled thousands of patients; while the PLATO study initially demonstrated its effectiveness in the immediate treatment of acute coronary syndromes, the PEGASUS study documented the benefit of prolonging this treatment beyond 12 months from the heart attack. Over the past few months, two new randomized clinical trials have been published that have seen the use of ticagrelor in different clinical settings. The TWILIGHT study showed that in high-risk patients who completed 3 months of double antiplatelet drugs after coronary angioplasty, ticagrelor monotherapy is associated with a 44% reduction in the risk of clinically relevant bleeding in the absence of an increase in the ischaemic risk. The THEMIS study instead concluded that in the population of diabetics with stable coronary artery disease, but without a history of heart attack or stroke, a strategy that involves the addition of ticagrelor to the acetylsalicylic acid is not advisable as in the face of a benefit in the prevention of events ischaemic an increased risk of bleeding has been observed. Only in the subgroup of diabetic patients with a history of previous angioplasty would a more powerful antithrombotic therapy seem to be advantageous.

Persistent Interstitial Pulmonary Emphysema-like Cyst Associated with Metastatic Synovial Sarcoma

2000 ◽  
Vol 3 (4) ◽  
pp. 391-393 ◽  
Author(s):  
Marta C. Cohen ◽  
Ricardo Drut
Keyword(s):  
Respiratory Distress ◽  
Pulmonary Disease ◽  
Synovial Sarcoma ◽  
Pulmonary Emphysema ◽  
Assisted Ventilation ◽  
Preterm Neonates ◽  
Inner Surface ◽  
Cystic Changes ◽  
History Of ◽  
The Right

Interstitial pulmonary emphysema is characterized by the presence of gas dissecting the interstitial tissues of the lung. Clinically, it may be acute or persistent, and the latter can be further categorized as localized or diffuse. Usually, it appears in preterm neonates with a history of assisted ventilation or respiratory distress. Although far from frequent, the localized variety of persistent interstitial pulmonary emphysema (PIPE) can develop spontaneously in full-term babies or infants without any obvious underlying pulmonary disease. Histologically, PIPE is characterized by the presence of uni- and multinucleated histiocytes lining the inner surface of the cysts. In this report, we describe a 15-year-old male with synovial sarcoma (SS) of the right ankle diagnosed 4 years previously who developed pulmonary metastasis, one of which presented cystic changes with features of PIPE.

scholarly journals Diagnosing α1-antitrypsin deficiency: how to improve the current algorithm

2015 ◽  
Vol 24 (135) ◽  
pp. 52-57 ◽  
Author(s):  
Noel G. McElvaney
Keyword(s):  
Rare Variants ◽  
Risk Groups ◽  
Laboratory Diagnosis ◽  
Chronic Obstructive ◽  
European Respiratory Society ◽  
Obstructive Pulmonary Disease ◽  
The Past ◽  
Antitrypsin Deficiency ◽  
History Of ◽  
Current Algorithm

Over the past 10–15 years, the diagnosis of α1-antitrypsin deficiency (AATD) has markedly improved as a result of increasing awareness and the publication of diagnostic recommendations by the American Thoracic Society (ATS)/European Respiratory Society (ERS). Nevertheless, the condition remains substantially underdiagnosed. Furthermore, when AATD is diagnosed there is a delay before treatment is introduced. This may help explain why AATD is the fourth most common cause of lung transplantation. Clearly we need to do better. The ATS/ERS recommend testing high-risk groups, such as: all chronic obstructive pulmonary disease patients; all nonresponsive asthmatic adults/adolescents; all cases of cryptogenic cirrhosis/liver disease; subjects with granulomatosis with polyangitis; bronchiectasis of unknown aetiology; panniculitis and first-degree relatives of patients with AATD. In terms of laboratory diagnosis, measurement of α1-antitrypsin levels will identify patients with protein deficiency, but cannot differentiate between the various genetic subtypes of AATD. Phenotyping is the current gold standard for detecting rare variants of AATD (except null variants), while advances in molecular diagnostics are making genotyping more effective. An accurate diagnosis facilitates the physician's ability to actively intervene with measures such as smoking cessation and perhaps augmentation therapy, and it will also help provide a better understanding of the natural history of the disease.

scholarly journals Alpha-1 Antitrypsin Deficiency and Risk of Lung Cancer in Never-Smokers: A Multicentre Case-Control Study

2021 ◽  
Author(s):  
Ramón Antonio Tubío-Pérez ◽  
María Torres-Durán ◽  
María Esmeralda García-Rodríguez ◽  
Cristina Candal-Pereira ◽  
Julia Rey-Brandariz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Case Control Study ◽  
Case Control ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Never Smokers ◽  
Epidemiological Characteristics ◽  
Control Study

Abstract Background Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although its principal risk factor is smoking habit, there are genetic mutations, such as alpha-1 antitrypsin deficiency (AATD), that have been related with increased risk This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype. Methods A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were patients with LC, and controls were patients, all never-smokers, undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype. Results The study included 457 cases (42%) and 631 controls (58%), with a predominance of women. The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS. Conclusions No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. Even so, new studies are required to provide fuller information in this regard with respect to never-smokers, and possibly even include previous respiratory diseases.

scholarly journals Lifestyle is associated with atrial fibrillation development in patients with type 2 diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chan Soon Park ◽  
Kyung-Do Han ◽  
Eue-Keun Choi ◽  
Da Hye Kim ◽  
Hyun-Jung Lee ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alcohol Consumption ◽  
Vigorous Physical Activity ◽  
Previous History ◽  
Lifestyle Behaviors ◽  
Increased Risk ◽  
History Of ◽  
Never Smokers ◽  
New Onset

AbstractWe evaluated the impacts of lifestyle behaviors, namely smoking, alcohol consumption, and physical activity, on the development of new-onset AF in patients with DM. Using the Korean Nationwide database, we identified subjects diagnosed with type 2 DM and without previous history of AF between 2009 and 2012. Self-reported lifestyle behaviors were analyzed. Among 2,551,036 included subjects, AF was newly diagnosed in 73,988 patients (median follow-up 7.1 years). Both ex-smokers (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02–1.07) and current smokers (HR 1.06, 95% CI 1.03–1.08) demonstrated a higher risk of AF than never smokers. Patients with moderate (15–29 g/day) (HR 1.12, 95% CI 1.09–1.15) and heavy (≥ 30 g/day) (HR 1.24, 95% CI 1.21–1.28) alcohol consumption exhibited an increased risk of AF, while subjects with mild alcohol consumption (< 15 g/day) (HR 1.01, 95% CI 0.99–1.03) had an AF risk similar to that of non-drinkers. Patients who engaged in moderate-to-vigorous physical activity showed a lower risk of AF (HR 0.93, 95% CI 0.91–0.94) than those who did not. This study suggests that smoking, alcohol consumption, and physical activity are associated with new-onset AF in patients with DM, and lifestyle management might reduce the risk of AF in this population.

Influence of smoking on aneurysm recurrence after endovascular treatment of cerebrovascular aneurysms

2018 ◽  
Vol 128 (4) ◽  
pp. 992-998 ◽  
Author(s):  
John Futchko ◽  
Jordan Starr ◽  
Darryl Lau ◽  
Matthew R. Leach ◽  
Christopher Roark ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Recurrence Rate ◽  
Endovascular Repair ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Aneurysms ◽  
Smoking History ◽  
Increased Risk ◽  
History Of ◽  
Never Smokers

OBJECTIVESmoking is a known risk factor for aneurysm development and aneurysmal subarachnoid hemorrhage, as well as subsequent vasospasm in both untreated individuals and patients who have undergone surgical clipping of cerebrovascular aneurysms. However, there is a lack of data in the current scientific literature about the long-term effects that smoking has on the integrity of endovascular repairs of cerebral aneurysms. This study was designed to determine if any smoking history increased the risk of poorer outcomes and/or aneurysm recurrence in patients who have had endovascular repair of cerebral aneurysms.METHODSThe authors retrospectively analyzed the medical records of patients admitted to the University of Michigan Health System from January 1999 to December 2011 with coiled aneurysms and angiography, CT angiography, or MR angiography follow-up. Patients were identified and organized based on many criteria including age, sex, smoking history, aneurysm recurrence, aneurysm location, and Hunt and Hess grade. Analysis was targeted to the patient population with a history of smoking. Bivariate chi-square tests were used to analyze the association between a positive smoking history and documented aneurysm recurrence and were adjusted for potential confounders by fitting multivariate logistic regression models of recurrence.RESULTSA total of 247 patients who had undergone endovascular treatment of 296 documented cerebral aneurysms were included in this study. The recurrence rate among all patients treated with endovascular repair was 24.3%, and the average time to the most recent follow-up imaging studies was 1.62 years. Smokers accounted for 232 aneurysms and were followed up for an average of 1.57 years, with a recurrence rate of 26.3%. Never smokers accounted for the remaining 64 aneurysms and were followed up for an average of 1.82 years, with a recurrence rate of 17.2%. Multivariate analysis revealed that, after controlling for potential confounders, a history of smoking—whether current or former—was associated with a significantly increased risk of aneurysm recurrence. The odds ratios for aneurysm recurrence for current and former smokers were 2.739 (95% CI 1.127–7.095, p = 0.0308) and 2.698 (95% CI 1.078–7.212, p = 0.0395), respectively, compared with never smokers.CONCLUSIONSA positive smoking history is associated with a significantly increased risk of aneurysm recurrence in patients who have undergone endovascular repair of a cerebral aneurysm, compared with the risk in patients who have never smoked.

Sign in / Sign up

Export Citation Format

Share Document