scholarly journals The Emerging Role of Proteases in Alpha-1 Antitrypsin Deficiency and Beyond

2021 ◽  
pp. 00494-2021
Author(s):  
Aishath Fazleen ◽  
Tom Wilkinson
Keyword(s):  
Serine Proteases ◽  
Treatment Options ◽  
Disease Process ◽  
Cathepsin G ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Alpha-1 Antitrypsin Deficiency (AATD) has been historically under-recognised and under-diagnosed; recently it has begun to receive greater interest in terms of attempts at deeper elucidation of pathology and treatment options. However, the concept of disease phenotypes within AATD (emphysema, chronic bronchitis, bronchiectasis, or a combination of phenotypes) has not been proposed or studied. Of the 3 Neutrophil Serine Proteases (NSPs), Neutrophil Elastase (NE) was historically believed to be the sole contributor to disease pathology in AATD. Recently, Proteinase-3 (PR3) has been increasingly studied as an equal, if not greater, contributor to the disease process. Cathepsin G (CG), however, has not been extensively evaluated in this area. Matrix metalloproteinases (MMPs) have also been mentioned in the pathogenesis of AATD but have not been widely explored. This article considers the available evidence for differential protease activity in patients with AATD, including the contribution to distinct phenotypes of the disease. Due to limited literature in this area, extrapolations from studies of other chronic lung diseases with similar phenotypes, including chronic obstructive pulmonary disease (COPD) and bronchiectasis have been made. We consider a new framework of understanding defined by protease driven endotypes of disease which may lead to new opportunities for precision medicine.

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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