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Lung Neutrophil Burden Correlates With Increased Pro-Inflammatory Cytokines and Decreased Lung Function in Individuals With α1-Antitrypsin Deficiency*

F. Rouhani; G. Paone; N. K. Smith; P. Krein; P. Barnes; Mark L. Brantly
Author and Funding Information

*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



Chest. 2000;117(5_suppl_1):250S-251S. doi:10.1378/chest.117.5_suppl_1.250S
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Extract

Abbreviations: α1AT = α1-antitrypsin; ANEC = antineutrophil elastase capacity; ELF = epithelial lining fluid; IL = interleukin; NE = neutrophil elastase

Individuals with α1-antitrypsin (α1AT) 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 α1AT-deficient individuals, we quantified neutrophil elastase (NE), α1AT, NE-α1AT complexes, antineutrophil elastase capacity (ANEC), and interleukin (IL)-8, IL-1β, and IL-6 in BAL fluid. Twenty-two individuals with α1AT 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 α1AT, NE, ANEC, IL-8, IL-6, IL-1β, and total neutrophils (p = 0.0001, 0.0015, 0.0001, 0.0157, 0.0006, 0.0271, and 0.0296, respectively) between individuals with α1AT 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 α1AT 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 α1AT 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 α1AT deficiency (p = 0.049 and 0.0141, respectively). These observations are consistent with the presence of lower respiratory tract inflammation in individuals with α1AT deficiency with near normal lung function.

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