SLPI deficiency in cystic fibrosis much worse in P aeruginosa-infected female patients
The presence of Pseudomonas aeruginosa worsens an already deficient airway secretory leukocyte protease inhibitor (SLPI), an antiprotease that helps prevent tissue damage, in patients with cystic fibrosis (CF), reports a study. Moreover, female patients show markedly lower SLPI levels than males.
“[A] reduced antiprotease to protease ratio is associated with accelerated lung function decline,” the authors said. “Treatment of an exacerbation is accompanied by partial recovery of antiprotease defences and significant improvement in lung function, an important clinical outcome.”
In this study, lung function and sputum SLPI and neutrophil elastase (NE, an important host defence against lung pathogens) levels were assessed from P aeruginosa-infected and noninfected CF patients (median age at recruitment 20 years) during different phases of clinical disease. Healthy, never smokers were included as control participants.
The authors also determined the sputum total cell counts (TCC) and colony forming units of P aeruginosa in each sputum sample.
CF patients with or without infection had significantly lower sputum SLPI and higher NE levels compared with those in healthy controls. However, the presence of P aeruginosa exacerbated such parameters. Notably, female patients with chronic P aeruginosa infection showed significantly lower sputum SLPI levels than males (p<0.001).
Higher sputum SLPI levels contributed to a significantly reduced rate of longitudinal decline in forced expiratory volume in 1 second (FEV1)% predicted (p<0.05).
Treatment with antibiotics among infected patients resulted in a significant reduction in sputum TCC level and a substantial increase in SLPI levels, which were associated with improved lung function.
“Maintaining a homeostatic balance between proteases such as NE and antiproteases such as SLPI, is important to prevent tissue damage,” the authors said. “In the CF lung, elevated protease levels and impaired antiprotease defences contribute to tissue destruction.”