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  • Title: Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Comparison with interstitial lung disease and evaluation of the effect of intravenously administered antibiotic therapy.
    Author: Meyer KC, Lewandoski JR, Zimmerman JJ, Nunley D, Calhoun WJ, Dopico GA.
    Journal: Am Rev Respir Dis; 1991 Sep; 144(3 Pt 1):580-5. PubMed ID: 1892298.
    Abstract:
    In cystic fibrosis (CF), extracellular lung matrix is progressively damaged, neutrophils invade the air spaces, and activated neutrophils may release large amounts of neutrophil elastase (NE). Although alpha 1-antiprotease (alpha 1-AP) binds and inactivates NE and is the major antielastase of the lower respiratory tract, antielastase defenses may be overwhelmed in CF, leading to progressive lung damage. To determine whether the ability of alpha 1-AP to neutralize NE is impaired in CF, we compared NE activity in bronchoalveolar lavage (BAL) fluid and human neutrophil elastase/alpha 1-antiprotease (NE/alpha 1-AP) complex in both BAL fluid and peripheral blood serum from patients with CF, normal volunteers, and patients with interstitial lung disease. We detected a considerable amount of NE activity in BAL fluid from all but one patient with CF but none in that from normal volunteers or from patients with interstitial lung disease. Although in interstitial lung disease there was a significant correlation between increased NE/alpha 1-AP complex in BAL or peripheral blood and the degree of neutrophil influx, NE/alpha 1-AP complex was disproportionately low in CF BAL compared with significantly elevated values in serum. These data suggest that in CF, alpha 1-AP-mediated defense against free NE in the lower respiratory tract is significantly impaired, and high levels of uncomplexed, enzymatically active, NE are present in CF respiratory secretions. To determine whether intravenously administered antipseudomonal antibiotic therapy for exacerbations of CF lung disease diminished the amount of free NE in respiratory secretions, we used BAL to investigate the effect of such therapy on neutrophils and NE in patients with CF colonized with pseudomonads.(ABSTRACT TRUNCATED AT 250 WORDS)
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