A Review of Alpha-1 Antitrypsin Deficiency

Justin Ranes; James K. Stoller

doi:10.1055/s-2005-869536

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2005; 26(2): 154-166
DOI: 10.1055/s-2005-869536

A Review of Alpha-1 Antitrypsin Deficiency

Justin Ranes¹ , James K. Stoller¹ ^, ² ^, ³

¹Department of Pulmonary, Allergy, and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio
²Division of Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio
³Section of Respiratory Therapy, The Cleveland Clinic Foundation, Cleveland, Ohio

Abstract

ABSTRACT

Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from degrading normal host tissue. Individuals who are deficient in AAT (those with levels < 11μmol/L) are at risk for developing such clinical manifestations as emphysema, cirrhosis, panniculitis, and anticytoplasmic neutrophilic antibody (C-ANCA) -positive vasculitis (Wegener's granulomatosis). Estimates suggest that 75 to 85% of those with severe deficiency of AAT will develop emphysema. Smoking appears to be the most important risk factor for the development of emphysema among AAT deficient persons. Severe deficiency of AAT also seems to be associated with a shorter lifespan. Among smokers, mild to moderate reductions in AAT levels may be associated with a more rapid decline in lung function. Diagnosis of AAT deficiency is made by measuring serum levels of AAT and, if reduced, an effort should then be made to identify the genetic abnormality responsible for the reduction. A recent evidence-based review has offered testing recommendations for AAT deficiency and includes the recommendation that all patients with COPD be tested for AAT deficiency. Augmentation with an intravenous form of purified pooled human plasma has been shown to increase the serum levels of AAT among deficient patients and its use appears to impact the rate of forced expiratory volume in 1 second (FEV₁) decline and overall survival; to date, no confirmatory, large, prospective, randomized trials are available.

KEYWORDS

Alpha 1-antitrypsin - emphysema - genetic disorders - chronic obstructive pulmonary disease

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Referenzen

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James K StollerM.D. M.S.

Department of Pulmonary, Allergy, and Critical Care Medicine/A90

The Cleveland Clinic Foundation, 9500 Euclid Ave.

Cleveland, OH 44195

eMail: Stollej@ccf.org