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1-Antitrypsin Deficiency*
* From the Pulmonary-Critical Care Medicine Branch (Drs. Rouhani, Paone, Smith, Krein, and Barnes), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and the University College of Medicine (Dr. Brantly), Gainesville, FL. Funding by the Division of Intramural Research, NHLBI, NIH, and the University of Florida.
Correspondence to: Mark L. Brantly, University of Florida, P.O. Box 100225 JHMHC, Gainesville, FL 32610
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1AT =
1-antitrypsin; ANEC =
antineutrophil elastase capacity; ELF = epithelial lining fluid; IL =
interleukin; NE = neutrophil elastase
Individuals
with
1-antitrypsin (
1AT) deficiency
develop severe destructive lung disease much earlier and undergo more
rapid decline in lung function than do the general population of
individuals with COPD. To identify factors associated with lung
destruction early in the development of lung disease in
1AT-deficient individuals, we quantified neutrophil
elastase (NE),
1AT, NE-
1AT complexes,
antineutrophil elastase capacity (ANEC), and interleukin (IL)-8,
IL-1ß, and IL-6 in BAL fluid. Twenty-two individuals with
1AT deficiency and mild functional lung impairment (mean
FEV1, 101 ± 3.0% of predicted) were compared with 14
normal individuals (mean FEV1, 107 ± 4.0% of
predicted). Enzyme-linked immunosorbent assays were used for all
measurements, and the actual epithelial lining fluid (ELF)
concentration was estimated using the urea method. There were
significant differences in ELF concentrations of
1AT,
NE, ANEC, IL-8, IL-6, IL-1ß, and total neutrophils (p = 0.0001,
0.0015, 0.0001, 0.0157, 0.0006, 0.0271, and 0.0296, respectively)
between individuals with
1AT deficiency and normal
subjects. A significant positive correlation was noted between the IL-8
and NE, ELF total neutrophils, or IL-6 in individuals with
1AT deficiency (p = 0.0041, 0.0053, and 0.0059,
respectively). There was a significant negative correlation between
initial FEV1 (% predicted) and NE or ELF total neutrophils
in individuals with
1AT deficiency (p = 0.0273 and
0.0414, respectively). In addition, there was a negative correlation
between the rate of decline of FEV1 and NE or ELF total
neutrophils in individuals with
1AT deficiency
(p = 0.049 and 0.0141, respectively). These observations are
consistent with the presence of lower respiratory tract inflammation in
individuals with
1AT deficiency with near normal lung
function.
This article has been cited by other articles:
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R A Sandhaus {alpha}1-Antitrypsin deficiency {middle dot} 6: New and emerging treatments for {alpha}1-antitrypsin deficiency Thorax, October 1, 2004; 59(10): 904 - 909. [Abstract] [Full Text] [PDF] |
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R. A. Stockley Neutrophils and the Pathogenesis of COPD* Chest, May 1, 2002; 121(5_suppl): 151S - 155S. [Full Text] [PDF] |
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