Protease-antiprotease imbalance in the lungs of children with cystic fibrosis.

TLDR

Cystic fibrosis lungs suffer chronic purulent bronchitis that progresses to pulmonary insufficiency, largely driven by neutrophil elastase released by neutrophils on the airway epithelium. The study aimed to identify when neutrophil‑dominated inflammation begins in CF children and how it affects the neutrophil elastase–anti‑elastase balance on the airway surface. Researchers measured neutrophil elastase and its inhibitors in the epithelial lining fluid of 27 stable CF children aged 1–18 years. Even with normal alpha‑1‑antitrypsin and SLPI levels, 25 of 27 children displayed neutrophil‑dominated inflammation, active elastase was present in 20 children (including two 1‑year‑olds), and most inhibitors were complexed or degraded, indicating a chronic imbalance established by age one that could drive lung damage.

Abstract

Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/microliters ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage.