The continuing need for dornase alfa for extracellular airway DNA hydrolysis in the era of CFTR modulators

Expert Rev Respir Med. 2024 Sep;18(9):677-691. doi: 10.1080/17476348.2024.2394694. Epub 2024 Aug 30.

Abstract

Introduction: The availability of cystic fibrosis transmembrane conductance regulator (CFTR) modulators opens the possibility of discontinuing some chronic pulmonary therapies to decrease cystic fibrosis (CF) treatment burden. However, CFTR modulators may not adequately address neutrophilic inflammation, which contributes to a self-perpetual cycle of viscous CF sputum, airway obstruction, inflammation, and lung function decline.

Areas covered: This review discusses the emerging role of neutrophil extracellular traps in CF and its role in CF sputum viscosity, airway obstruction, and inflammation, based on a literature search of PubMed (1990-present). We summarize clinical trials and real-world studies that support the efficacy of dornase alfa (Pulmozyme) in improving lung function and reducing pulmonary exacerbation in people with CF (PwCF), and we discuss the potential role of dornase alfa in reducing airway inflammation. We also examine the findings of short-term trials evaluating the discontinuation of mucoactive therapy in PwCF receiving CFTR modulators.

Expert opinion: Long-term studies are needed to assess the impact of discontinuing mucoactive therapy in PwCF who are clinically stable while receiving CFTR modulatory therapy. Treatment decisions should take into account the severity of underlying lung disease. People with advanced CF will likely require ongoing mucoactive therapy.

Keywords: CFTR modulators; Cystic fibrosis; airway inflammation; dornase alfa; neutrophil extracellular traps.

Publication types

  • Review

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator* / metabolism
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / metabolism
  • Cystic Fibrosis* / physiopathology
  • DNA
  • Deoxyribonuclease I* / therapeutic use
  • Expectorants / therapeutic use
  • Extracellular Traps* / drug effects
  • Extracellular Traps* / metabolism
  • Humans
  • Hydrolysis
  • Lung / drug effects
  • Lung / metabolism
  • Lung / physiopathology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Sputum / metabolism

Substances

  • dornase alfa
  • Deoxyribonuclease I
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Recombinant Proteins
  • CFTR protein, human
  • Expectorants
  • DNA