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      Obstacles to Early Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency: Current Perspectives

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          Abstract

          This review summarizes the current research and outlooks regarding the obstacles to diagnosing and treating early alpha-1-antitrypsin deficiency (AATD). It draws on prior systematic reviews and expert surveys to discover precisely what difficulties exist in early diagnosis and treatment of AATD and elucidate potential solutions to ease these difficulties. The perceived rarity of AATD may translate to a condition poorly understood by primary care physicians, and even many respiratory physicians, which results in opportunities for diagnosis being missed, especially in mild or asymptomatic patients. There are diagnostic techniques involving biomarkers and home testing methods which could improve the rate of early diagnosis. With respect to treatment, AATD involves treating two separate pathologies, lung disease and liver disease. The only specific AATD treatment, augmentation therapy, has proven ability in treating lung disease but not liver disease. Alpha-1-antitrypsin (AAT) synthesized in the liver can form damaging polymers that also result in reduced circulating AAT levels and, whilst liver transplantation is used to effectively treat AATD, it is inappropriate in early disease. Novel therapeutic areas such as gene editing and increasing autophagy are therefore being researched as future treatments. Ultimately, diagnosis and treatment are intrinsically linked in AATD, with earlier diagnosis leading to better treatment options and thus better patient outcomes.

          Most cited references72

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          The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease.

          Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible limitation in airflow. A physiological variable--the forced expiratory volume in one second (FEV1)--is often used to grade the severity of COPD. However, patients with COPD have systemic manifestations that are not reflected by the FEV1. We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients. We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort: the body-mass index (B), the degree of airflow obstruction (O) and dyspnea (D), and exercise capacity (E), measured by the six-minute-walk test. We used these variables to construct the BODE index, a multidimensional 10-point scale in which higher scores indicate a higher risk of death. We then prospectively validated the index in a cohort of 625 patients, with death from any cause and from respiratory causes as the outcome variables. There were 25 deaths among the first 207 patients and 162 deaths (26 percent) in the validation cohort. Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency, 14 percent to myocardial infarction, 12 percent to lung cancer, and 13 percent to other causes. Patients with higher BODE scores were at higher risk for death; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 (95 percent confidence interval, 1.26 to 1.42; P<0.001), and the hazard ratio for death from respiratory causes was 1.62 (95 percent confidence interval, 1.48 to 1.77; P<0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV1 (0.74 vs. 0.65). The BODE index, a simple multidimensional grading system, is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD. Copyright 2004 Massachusetts Medical Society
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            Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial.

            The efficacy of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency has not been substantiated by a randomised, placebo-controlled trial. CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema than spirometry is, so we aimed to assess the efficacy of augmentation treatment with this measure.
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              Alpha1-Antitrypsin Deficiency

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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                tcrm
                tcriskman
                Therapeutics and Clinical Risk Management
                Dove
                1176-6336
                1178-203X
                16 December 2020
                2020
                : 16
                : 1243-1255
                Affiliations
                [1 ]Institute of Applied Health Research, University of Birmingham , Birmingham, UK
                [2 ]University Hospitals Birmingham , Birmingham, UK
                Author notes
                Correspondence: Alice M Turner Institute of Applied Health Research, University of Birmingham , Edgbaston, BirminghamB15 2TT, UKTel +44 121 371 3885 Email a.m.turner@bham.ac.uk
                Author information
                http://orcid.org/0000-0002-2562-0295
                http://orcid.org/0000-0002-5947-3254
                Article
                234377
                10.2147/TCRM.S234377
                7751439
                33364772
                ce550cf1-51a0-455d-824b-1fca19c7db6e
                © 2020 Quinn et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 06 October 2020
                : 30 November 2020
                Page count
                Figures: 1, Tables: 5, References: 74, Pages: 13
                Categories
                Review

                Medicine
                emphysema,cirrhosis,diagnostic screening programs,chronic obstructive pulmonary disease

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