Advances in managing COPD related to α1 -antitrypsin deficiency: An under-recognized genetic disorder

Abstract

α₁ -Antitrypsin deficiency (AATD) predisposes individuals to chronic obstructive pulmonary disease (COPD) and liver disease. Despite being commonly described as rare, AATD is under-recognized, with less than 10% of cases identified. The following is a comprehensive review of AATD, primarily for physicians who treat COPD or asthma, covering the genetics, epidemiology, clinical presentation, screening and diagnosis, and treatments of AATD. For patients presenting with liver and/or lung disease, screening and diagnostic tests are the only methods to determine whether the disease is related to AATD. Screening guidelines have been established by organizations such as the World Health Organization, European Respiratory Society, and American Thoracic Society. High-risk groups, including individuals with COPD, nonresponsive asthma, bronchiectasis of unknown etiology, or unexplained liver disease, should be tested for AATD. Current treatment options include augmentation therapy with purified AAT for patients with deficient AAT levels and significant lung disease. Recent trial data suggest that lung tissue is preserved by augmentation therapy, and different dosing schedules are currently being investigated. Effective management of AATD and related diseases also includes aggressive avoidance of smoking and biomass burning, vaccinations, antibiotics, exercise, good diet, COPD medications, and serial assessment.

Keywords: COPD; asthma; augmentation therapy; emphysema; α1-antitrypsin; α1-antitrypsin deficiency.

Figure 1

CT scans showing extensive emphysematous damage to the lungs. A, Axial plane of thorax; B, Coronal plane of thorax. CT, computed tomography. CT scans were kindly provided by Prof. Dr. Andreas Rembert Koczulla, Fachzentrum für Pneumologie Schön Klinik Berchtesgadener Land, Germany, and Klinik für Pneumologie, Marburg, Germany

Figure 2

Liver damage in patients with α₁‐antitrypsin deficiency. A, Periodic acid Schiff diastase (PAS‐d) staining showing intracytoplasmic accumulation of PAS‐d–resistant material; B, Immunohistochemical staining of the case patient's hepatocytes; and C, Control immunohistochemical staining of a known α₁‐antitrypsin–deficient patient. From: Rider and Craig61

Figure 3

Rates of lung density decrease at total lung capacity versus trough A1PI serum concentrations achieved (RAPID trial). A1PI, α₁ proteinase inhibitor. From: Chapman et al80

Figure 4

Estimated lung density decline over 48 mo (RAPID trial). n, number of patients. From: McElvaney et al100

Figure 5

Changes in DES/IDES plasma levels from baseline in the RAPID trials. A1PI, α₁ proteinase inhibitor; DES/IDES, desmosine/isodesmosine; n, number of patients. Figure used with permission from Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation101