Unopposed neutrophil elastase in bronchoalveolar lavage from transplant recipients with cystic fibrosis.
Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteolytic activity are found in lower respiratory tract secretions from most patients with advanced cystic fibrosis (CF). To determine whether antielastase defenses may be overwhelmed in epithelial lining fluid after lung transplantation, we measured NE activity (cleavage of the specific substrate, MeO-Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained for surveillance or diagnostic purposes at various intervals (1 mo to 7 yr after transplantation) from 52 recipients who had undergone double or bilateral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had >= 10(5) colony forming units (cfu) of Pseudomonas aeruginosa in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had developed obliterative bronchiolitis (OB), but only 8 of the 38 subjects without unopposed NE activity had OB (p = 0. 002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF patients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE activity in BAL from lung allografts of patients with CF is associated with progressive, irreversible OB and graft failure.
Nunley
D
D
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and University of Wisconsin Medical School, Madison, Wisconsin, USA.
Dauber
J
J
Iacono
A
A
Keenan
R
R
Zeevi
A
A
Cornwell
R
R
Love
R
R
Meyer
K
K
Soergel
P
P
Peterson
K
K
D000293:Adolescent; D000328:Adult; D001989:Bronchiolitis Obliterans / Q000150:complications / Q000201:enzymology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000032:analysis*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D011184:Postoperative Period
D019272:Leukocyte Elastase