Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry.
OBJECTIVE
To clarify the mortality rate and causes of death of individuals with alpha(1)-antitrypsin (AAT) deficiency, the Death Review Committee (DRC) of the National Heart, Lung, and Blood Institute Registry of Individuals with Severe AAT Deficiency reviewed all available medical records regarding the deaths of study subjects during Registry follow-up (up to 7.2 years).


METHODS
Individual determinations by each member of the three-person DRC led to consensus judgments regarding the underlying cause and the immediate and contributing causes of death.


RESULTS
Of the 1,129 Registry subjects, 204 died (18.1%) [approximately 3%/yr]. Record availability permitted detailed review in 120 decedents, and death certificates were available in 56 of the remaining 84 subjects (67%). Emphysema and cirrhosis were the most common underlying causes of death (72% and 10%, respectively), with malignancy and diverticulitis accounting for 3% of deaths each. To assess attributable mortality, standardized mortality ratio analysis was performed and indicated that excess mortality was ascribable entirely to lung and liver disease.


CONCLUSIONS
We conclude that severe AAT deficiency poses a significant threat to health, that severe airflow obstruction is a major determinant of mortality, and that liver and lung disease account for the excess mortality in affected individuals. These findings support current efforts to enhance diagnostic recognition and treatment of AAT-deficient individuals.
Stoller
James K
JK
Department of Pulmonary, Allergy, and Critical Care Medicine, The Cleveland Clinic Foundation, 9500 Euclid Ave, A90, Cleveland, OH 44195, USA. stollej@ccf.org
Tomashefski
Joseph
J
Crystal
Ronald G
RG
Arroliga
Alejandro
A
Strange
Charlie
C
Killian
Dermot N
DN
Schluchter
Mark D
MD
Wiedemann
Herbert P
HP
D000328:Adult; D000368:Aged; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D012720:Severity of Illness Index; D013997:Time Factors; D019896:alpha 1-Antitrypsin Deficiency / Q000401:mortality*