IS Case 415: Alpha-1 antitrypsin deficiency
Imaging Sciences URMC 2010
Publication Date: 2010-08-27
Alpha-1 antitrypsin deficiency
Alpha-1 antitrypsin deficiency (A1AD) is the only genetic abnormality specifically known to cause COPD. The disease is autosomal dominant and has been linked to a gene on chromosome 14. The gene product, Alpha-1 Antitrypsin, blocks the effects of proteolytic enzymes. A protease-antiprotease imbalance is created in its absence. This makes the lung more susceptible to airway damage induced by infection and inhaled toxins.
A1AD results in panlobular emphysema with uniform destruction of all components of the secondary pulmonary lobule. This is in contradistinction to centrilobular emphysema classically associated with cigarette smoke, which preferentially affects the centri-acinar respiratory bronchioles.
Patients with A1AD are at increased risk for asscoiated abnormalities including cirrhosis, necrotizing panniculitis, and Wegener's granulomatosis. Cirrhosis is uncommon, affecting 5-10% of patients with A1AD over the age of 50. In the lungs, the classic finding of lower zone emphysema occurs in 2/3. However findings can uncommonly be diffuse or even upper lobe predominant. Bronchiectasis and bronchial wall thickening are also seen in about 40%.
Lung disease is of course compounded by smoking, however cirrhosis is the major cause of mortality in nonsmokers with A1AD. Nonetheless, life expectancy is decreased in all patients with A1AD. Treatment consists of patient education, smoking cessation and prophylactic vaccinations. Prophylactic antibiotics are controversial and have been shown to be effective. Experimental treament with intravenous Alpha-1 antiprotease is expensive and inconvenient at this time. Gene therapy is being studied. Surgical lung volume reduction and transplant are reserved for patients with endstage disease.
- Webb W, Higgins C. Thoracic Imaging: Pulmonary and Cardiovascular Radiology. Philadelphia: Lippincott Williams & Wilkins, 2005.
- Churg A, Wright JL. Proteases and emphysema. Curr Opin Pulm Med. 2005 Mar;11(2):153-9. PMID: 15699789