Neutrophil mediators, Pseudomonas, and pulmonary dysfunction in cystic fibrosis.
Proteolytic enzymes derived from inflammatory cells or Pseudomonas aeruginosa may destroy lung matrix in cystic fibrosis (CF). Antielastases appear to be overwhelmed by large amounts of free neutrophil elastase (NE) activity in lower respiratory tract secretions, and proteolytic or oxidant stress is thought to account for such deficiency. The purpose of this study was to measure NE and myeloperoxidase activity in bronchoalveolar lavage fluid (BAL) from patients with CF and to correlate levels of these mediators with the degree of airflow obstruction and density of P. aeruginosa in BAL. We measured NE activity in BAL fluid from 14 patients with respiratory exacerbations of CF. NE complexed with alpha 1-antiprotease in peripheral blood was measured in 13 of the 14 patients subjected to BAL and in 21 additional patients who did not undergo BAL. Because oxidants generated by myeloperoxidase may contribute to increased elastase activity via inactivation of alpha 1-antiprotease, myeloperoxidase activity in BAL was also measured. We found that elastase activity in BAL correlated significantly with the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC ratio) (r = -0.80, p < 0.001) and FEV1 percent predicted (r = -0.62, p = 0.02). Myeloperoxidase activity also significantly correlated with airflow obstruction (FEV1/FVC ratio, r = -0.70, p = 0.005; FEV1 percent predicted, r = -0.52, p = 0.05). However, the degree of airflow obstruction, NE activity, myeloperoxidase activity, or total neutrophils in BAL did not correlate with the density of P. aeruginosa (CFU/ml) or total pathogen burden in BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Wisconsin Medical School, Madison.
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Meyer
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Zimmerman
D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology / Q000503:physiopathology*; D006801:Humans; D019272:Leukocyte Elastase; D008168:Lung / Q000382:microbiology; D008173:Lung Diseases, Obstructive / Q000209:etiology*; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000150:complications; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000150:complications; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000515:alpha 1-Antitrypsin; D009195:Peroxidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase