Unopposed neutrophil elastase in bronchoalveolar lavage from transplant recipients with cystic fibrosis

Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteo lytic activity are found in lower respiratory tract secretions from most pa tients with advanced cystic fibrosis (CF). To determine whether antielastas e defenses may be overwhelmed in epithelial lining fluid after lung transpl antation, we measured NE activity (cleavage of the specific substrate, MeO- Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained f or surveillance or diagnostic purposes at various intervals (1 mo to 7 yr a fter transplantation) from 52 recipients who had undergone double or bilate ral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had greater than or equal to 10(5) colony forming units (cfu) of Pseudomonas aeruginoso in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had dev eloped obliterative bronchiolitis (OB), but only 8 of the 38 subjects witho ut unopposed NE activity had OB (p = 0.002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF pat ients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE act ivity in BAL from lung allografts of patients with CF is associated with pr ogressive, irreversible OB and graft failure.