Alpha1-Antitrypsin Deficiency in COPD: Clinical Implications

, College of Physicians and Surgeons, Columbia University, NY

In This Article

Abstract and Introduction


In the setting of asthma, early emphysema due to alpha1-antitrypsin deficiency (alpha1-ATD) is an unusual and frequently missed diagnosis. Alpha1-ATD is one of the most common genetically-linked lethal diseases among Caucasians, affecting approximately 1 in every 4000 in the US; many cases remain undiagnosed. Alpha1-antitrypsin (alpha1-AT) is a serine protease inhibitor, a member of a large supergene family of "suicide serpins" that inactivate a specific group of proteases. Among these, alpha1-AT is the major physiologic inhibitor for neutrophil elastase and therefore controls elastase-mediated degradation of elastic tissue in the lung to maintain tissue integrity. Anti-elastase activity is significantly reduced in the lower respiratory tract in cases of alpha1-ATD, resulting in increased elastin breakdown, and predisposing affected individuals, particularly those who smoke, to a severe and life-threatening panacinar form of emphysema. Asthma is an inflammatory process in which the airways may become obstructed. Abnormal alpha1-AT phenotypes are associated with an increased prevalence and severity of asthma, suggesting that, under normal circumstances, alpha1-AT modulates the effect of inflammatory mediators involved in the pathogenesis of asthma. The development of asthma in patients with alpha1-ATD may further predispose them to rapid development of irreversible airway obstruction and emphysema. In a patient with asthma, family history of lung disease, prior smoking, or complaint of dyspnea not related to episodes of wheezing should alert the physician that hereditary emphysema may be present. In these patients, preventive measures including counseling to not smoke or smoking cessation, and adequate immunization against influenza should be instituted, and alpha1-AT replacement therapy may be therapeutic.


Early emphysema due to alpha1-antitrypsin deficiency (alpha1-ATD) in a young patient with asthma is an unusual and frequently missed diagnosis. Theoretical and clinical evidence supports the expectation that a significant proportion of patients with alpha1-ATD will present to their primary care physician with symptoms and signs of asthma.

Asthma leads to episodic but reversible airway obstruction and wheezing. The condition is easy to define clinically provided other sources of airway obstruction causing bronchial hyperreactivity and wheezing are absent.

In the case of alpha1-ATD, asthma and emphysema may coexist. Making the diagnosis is important because therapy for both conditions exists, most notably corticosteroids and aeroallergen avoidance for asthma and alpha1-antitrypsin (alpha1-AT) replacement therapy for those with emphysema resulting from alpha1-ATD. In addition, poorly controlled asthma may accelerate the deterioration of lung function in patients with alpha1-ATD (and perhaps also in those with non-alpha1 chronic obstructive pulmonary disease [COPD])


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.