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Alpha-1 antitrypsin deficiency

Definition
AATD is an inherited disorder caused by mutations in the SERPINA1 gene, leading to a deficiency or dysfunction of the AAT protein.
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Pathophysiology
The pathophysiology of AATD involves a deficiency in the AAT protein. The imbalance of proteases and antiproteases leads to unopposed neutrophil elastase activity and subsequent tissue damage in the lungs.
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Epidemiology
The prevalence of AATD in Europe is estimated at 20 per 100,000 population.
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Disease course
Clinically, patients with AATD often present with symptoms such as dyspnea, chronic cough, and recurrent respiratory infections. In some cases, the disease may also manifest as unexplained bronchiectasis. In rare cases, it can also lead to liver disease, including chronic hepatitis, cirrhosis, and HCC.
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Prognosis and risk of recurrence
The prognosis can vary widely among patients. The disease is generally progressive, with the potential for significant lung damage over time.
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Key sources
The following summarized guidelines for the evaluation and management of alpha-1 antitrypsin deficiency are prepared by our editorial team based on guidelines from the National Comprehensive Cancer Network (NCCN 2022), the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2022), the European Respiratory Society (ERS 2017), the Alpha-1 Foundation (Alpha-1 2016), the American Association for the Study of Liver Diseases (AASLD 2014), and the Canadian Thoracic Society (CTS 2012).
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Guidelines

1.Screening and diagnosis

Clinical presentation
Recognize that lung disease in AATD generally presents at a younger age than usual COPD and may be misdiagnosed as asthma.
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Recognize that patients with AATD are more likely to have basal emphysema than patients with usual COPD.
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  • Screening of family relatives

  • Indications for testing (lung disease)

  • Indications for testing (liver disease)

  • Indications for testing (vasculitis)

  • Indications for testing (panniculitis)

2.Diagnostic investigations

AAT levels: as per ERS 2017 guidelines, obtain quantitative measurement of AAT levels in the blood to identify AATD.
E

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  • Protein electrophoresis

  • Genetic testing

  • Pulmonary function testing

  • Chest imaging

3.Medical management

Setting of care: manage patients with AATD in supervision by reference centers of excellence at a national or regional level.
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  • Augmentation therapy

4.Nonpharmacologic interventions

Smoking cessation: advise smoking cessation and avoidance of exposure to tobacco in patients with AATD.
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5.Surgical interventions

Lung volume reduction surgery: as per ERS 2017 guidelines, consider performing surgical volume reduction and endobronchial valve placement in selected patients with AATD, with a careful appraisal of risks and benefits assessed by a multidisciplinary team experienced in lung volume reduction and AATD.
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  • Lung transplantation

  • Liver transplantation

6.Follow-up and surveillance

Surveillance for lung disease: as per ERS 2017 guidelines, obtain annual pulmonary function testing including post-bronchodilator FEV1 and gas transfer to monitor for disease progression.
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  • Surveillance for liver disease

  • Surveillance for HCC