Am. J. Respir. Crit. Care Med., Volume 164, Number 1, July 2001, 97-102

Neutrophils, Unopposed Neutrophil Elastase, and Alpha₁-Antiprotease Defenses Following Human Lung Transplantation

KEITH C. MEYER, DAVID R. NUNLEY, JAMES H. DAUBER, ALDO T. IACONO, ROBERT J. KEENAN, RICHARD D. CORNWELL, and ROBERT B. LOVE

Sections of Pulmonary and Critical Care Medicine and Cardiothoracic Surgery, University of Wisconsin Hospital and Clinics, Madison, Wisconsin; and Sections of Pulmonary and Critical Care Medicine and Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Neutrophils are sequestered in the newly transplanted lung after reperfusion or with infection, rejection, and chronic graft dysfunction. Because unopposed (free) neutrophil elastase (NE) released into bronchoalveolar secretions may injure the lung allograft and impair bacterial clearance, we assessed total neutrophil numbers, myeloperoxidase activity as an index of neutrophil influx and degranulation, alpha₁-antiprotease (₁-AP) concentrations, and unopposed NE activity in bronchoalveolar secretions from lung transplant recipients. Unopposed NE activity was present in bronchoalveolar lavage fluid (BALF) from recipients transplanted for emphysema associated with ₁-AP deficiency as well as recipients without such deficiency (171 of 2,137 BALF; 8%). Ten of 17 (59%) recipients with ₁-AP deficiency who were followed for at least 1 yr after transplant with multiple surveillance and diagnostic bronchoscopies had at least one BALF containing unopposed NE, usually associated with the presence of  10⁵ colony forming units/ml BALF of aerobic bacteria. In contrast, 19 of 58 (33%) with emphysema not associated with ₁-AP deficiency, 8 of 32 (25%) recipients with cystic fibrosis (CF), 6 of 16 (38%) with idiopathic pulmonary fibrosis (IPF), and 11 of 36 (31%) with other indications for transplant had unopposed NE in BALF. ₁-AP levels were significantly elevated in the early posttransplant time period and could be augmented considerably in ₁-AP-deficient recipients with episodes of infection or rejection. Our findings indicate that unopposed NE activity can be found in both ₁-AP-deficient and ₁-AP-sufficient recipients after transplantation, usually in association with endobronchial bacterial infection.

Keywords: bronchoalveolar lavage; lung transplantation; neutrophil; neutrophil elastase; ₁-antiprotease

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