Bronchiolitis obliterans syndrome after (heart-)lung transplantation. Impaired antiprotease defense and increased oxidant activity

Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1640-6. doi: 10.1164/ajrccm.160.5.9902012.


Increased numbers of neutrophils are a common finding in bronchoalveolar lavage fluid (BALF) samples obtained from patients after (heart-)lung transplantation [(H)LTX]. Since proteases and reactive oxygen species secreted by neutrophils are capable of causing substantial damage to the lung tissue if not counterbalanced by the antiprotease and antioxidant screen, we hypothesized that neutrophil products may play a role in the development of obliterative bronchiolitis (OB). A total of 72 BALF samples obtained from 33 patients after (H)LTX were evaluated. Sixteen of these patients were suffering from bronchiolitis obliterans syndrome (BOS) at the time of bronchoalveolar lavage (BAL). As a control, BALF samples from 17 healthy volunteers were analyzed. Anti-neutrophil elastase (NE) activity was quantified by a titration assay. Concentrations of alpha(1)-protease inhibitor (API), secretory leukocyte protease inhibitor (SLPI), NE-API complex, and myeloperoxidase (MPO) were measured by ELISA. Oxidized methionine [Met(O)] was quantified by high-performance liquid chromatography (HPLC). Epithelial lining fluid (ELF) from patients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI. Furthermore, a trend toward an increased NE activity and MPO concentration was observed. These findings suggest that neutrophils may be involved in the development of BOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchiolitis Obliterans / etiology*
  • Bronchiolitis Obliterans / metabolism
  • Bronchiolitis Obliterans / pathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Heart-Lung Transplantation / adverse effects*
  • Humans
  • Leukocyte Elastase / antagonists & inhibitors
  • Methionine / metabolism*
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Oxidants / metabolism*
  • Oxidation-Reduction
  • Peroxidase / analysis
  • Protease Inhibitors / metabolism*
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins / analysis
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors / analysis
  • alpha 1-Antitrypsin / analysis


  • Oxidants
  • Protease Inhibitors
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors
  • alpha 1-Antitrypsin
  • Methionine
  • Peroxidase
  • Leukocyte Elastase