scholarly journals The spectrum of clinical sequelae associated with alpha-1 antitrypsin deficiency

2021 ◽  
Vol 12_suppl ◽  
pp. 204062232199569
Author(s):  
Vickram Tejwani ◽  
James K. Stoller
Keyword(s):  
Case Series ◽  
Antineutrophil Cytoplasmic Antibody ◽  
The United States ◽  
Chronic Obstructive ◽  
Augmentation Therapy ◽  
Obstructive Pulmonary Disease ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Dominant Condition

Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal co-dominant condition that predisposes to the development of lung disease, primarily emphysema. Emphysema results from the breakdown of lung matrix elastin by proteases, including neutrophil elastase, a protease normally inhibited by AAT. AATD also predisposes to liver (cirrhosis) and skin (panniculitis) disease, and to vasculitis. The prevalence of AATD is estimated to be approximately 1 in 3,500 individuals in the United States. However, lack of awareness of AATD among some physicians, misperceptions regarding the absence of effective therapy, and the close overlap in symptoms with asthma and non-AATD chronic obstructive pulmonary disease are thought to contribute to under-recognition of the disease. In patients with AATD, treatment with intravenous AAT augmentation therapy is the only currently available treatment known to slow the progression of emphysema. Moreover, smoking cessation and other lifestyle interventions also help improve outcomes. Early diagnosis and intervention are of key importance due to the irreversible nature of the resultant emphysema. Liver disease is the second leading cause of death among patients with AATD and a minority of patients present with panniculitis or antineutrophil cytoplasmic antibody-associated vasculitis, thought to be directly related to AATD. Though no randomized trial has assessed the effectiveness of augmentation therapy for AATD-associated panniculitis, clinical experience and case series suggest there is a benefit. Other diseases putatively linked to AATD include aneurysmal disease and multiple neurological conditions, although these associations remain speculative in nature.

scholarly journals Medical Costs of Alpha-1 Antitrypsin Deficiency-Associated COPD in the United States

2019 ◽  
Author(s):  
Jan Sieluk ◽  
Julia F Slejko ◽  
Henry Silverman ◽  
Eleanor Perfetto ◽  
C. Daniel Mullins
Keyword(s):  
Index Date ◽  
Healthcare Resource ◽  
The United States ◽  
Chronic Obstructive ◽  
Augmentation Therapy ◽  
Copd Patients ◽  
Before And After ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Abstract Background There are limited data on economic aspects of the genetic variant of chronic obstructive pulmonary disease (COPD) in the context of the more prevalent form of COPD. The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among COPD patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis.Results The study population consisted of 8,881 patients (953 cases matched with 7,928 controls). The AATD-associated COPD cohort had higher expenditures and use of OV and OTH services, as well as OV, OP, ER, RX, and OTH before and after the index date, respectively. Adjusted total cost ratios for AATD-associated COPD patients as compared to controls were 2.04 [95% CI: 1.60 – 2.59] and 1.98 [95% CI: 1.55 – 2.52] while the incremental cost difference totaled $6,861 [95% CI: $3,025 - $10,698] and $5,772 [95% CI: $1,940 - $9,604] per patient before and after the index date, respectively.Conclusions Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar COPD patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.

scholarly journals Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know

2021 ◽  
Vol 12_suppl ◽  
pp. 204062232110101
Author(s):  
Igor Barjaktarevic ◽  
Michael Campos
Keyword(s):  
Lung Disease ◽  
Treatment Guidelines ◽  
Management Program ◽  
Lifestyle Changes ◽  
Chronic Obstructive ◽  
Augmentation Therapy ◽  
Lung Function Decline ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches. Lifestyle changes with avoidance of environmental pollutants, including tobacco smoke, improving exercise levels and nutritional status, all encompassed under a disease management program, are crucial pillars of AATD management. Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease. Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy). This intervention raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung. Radiologically, augmentation therapy reduces lung density loss over time, thus delaying disease progression. The effect of augmentation therapy on other lung-related outcomes, such as exacerbation frequency/length, quality of life, lung function decline, and mortality, are less clear and questions regarding dose optimization or route of administration are still debatable. This review discusses the rationale and available evidence for these interventions in AATD.

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.

scholarly journals Alpha 1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease patients: is systematic screening necessary?

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Cláudia Henrique da Costa ◽  
Arnaldo José Noronha Filho ◽  
Rosa Maria Fernambel Marques e Silva ◽  
Thaís Ferrari da Cruz ◽  
Valeria de Oliveira Monteiro ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Systematic Screening ◽  
Obstructive Pulmonary Disease ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals Genetics of COPD

2020 ◽  
Vol 82 (1) ◽  
pp. 413-431 ◽  
Author(s):  
Edwin K. Silverman
Keyword(s):  
Association Studies ◽  
Chronic Obstructive ◽  
Genome Wide Association Studies ◽  
Obstructive Pulmonary Disease ◽  
Functional Variants ◽  
Genome Wide ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Genomic Regions

Although chronic obstructive pulmonary disease (COPD) risk is strongly influenced by cigarette smoking, genetic factors are also important determinants of COPD. In addition to Mendelian syndromes such as alpha-1 antitrypsin deficiency, many genomic regions that influence COPD susceptibility have been identified in genome-wide association studies. Similarly, multiple genomic regions associated with COPD-related phenotypes, such as quantitative emphysema measures, have been found. Identifying the functional variants and key genes within these association regions remains a major challenge. However, newly identified COPD susceptibility genes are already providing novel insights into COPD pathogenesis. Network-based approaches that leverage these genetic discoveries have the potential to assist in decoding the complex genetic architecture of COPD.

scholarly journals Exhaled Nitric Oxide as a Biomarker in COPD and Related Comorbidities

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Mario Malerba ◽  
Alessandro Radaeli ◽  
Alessia Olivini ◽  
Giovanni Damiani ◽  
Beatrice Ragnoli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Exhaled Nitric Oxide ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Chronic Obstructive Pulmonary Disease (COPD) is defined as a disease characterized by persistent, progressive airflow limitation. Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation. In COPD fractional exhaled Nitric Oxide (FeNO) levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters. Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones. In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression. FeNO measurements may be useful in clinical setting to identify the level of airway inflammation,per seand in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment. Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD. In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development.

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