Breaking down lung defenses in Cystic Fibrosis

Cystic fibrosis patients develop chronic neutrophilic inflammation of the airways.  Neutrophils which help fight off bacterial infections also release peroxidases and proteases which can damage the lung tissues.  Neutrophil elastase which is one of the proteases elaborated by neutrophils can digest elastin; this is prevented by α-1-antitrypsin.  However, when there is excessive free neutrophil elastase this can overwhelm this protection.  A recent study has shown that neutrophil elastase activity in bronchoalveolar lavage (BAL) at 3 months of age was associated with early bronchiectasis (NEJM 2013; 368: 1963-70).

Design: 127 consecutive infants (from region of Western Australia) who were diagnosed with cystic fibrosis after newborn screening were recruited; however, 10 were too young and 3 were lost to followup due to relocation.  Most were followed for 3 years; 78 remained in the study at 36 months. Chest CT scans and BAL were performed at 3 months, 1 year, 2 years, and 3 years when patients were in stable clinical condition.

Bronchiectasis was identified by CT scan findings: “defined as a bronchus-to-artery ratio of more than 1.0 or the presence of a non tapering bronchus in the transverse plane.”

Key findings:

  • Point prevalence of bronchiectasis: 29.3% at 3 months, 31.5% at 1 year, 44.0% at 2 years and 61.5% at 3 years.
  • Free (unbound) neutrophil elastase activity in BAL fluid was a risk factor for bronchiectasis with an odds ratio of 3.02.  At 3 months of age, 23.3% had detectable neutrophil elastase activity in BAL fluid.
  • Other risk factors for bronchiectasis included meconium ileum (OR 3.17), and respiratory symptoms at time of CT (OR 2.27).

Take-home message: Damage happens to the lungs early in life. The related editorial (pg 2026) states “early cystic fibrosis lung disease is not ‘silent’ if you listen carefully.” To improve long-term outcome, early intervention will be necessary.

Related blog posts: