RT Journal Article
SR Electronic
T1 Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy
JF European Respiratory Review
JO EUROPEAN RESPIRATORY REVIEW
FD European Respiratory Society
SP 210241
DO 10.1183/16000617.0241-2021
VO 31
IS 163
A1 Holly R. Keir
A1 James D. Chalmers
YR 2022
UL http://err.ersjournals.com/content/31/163/210241.abstract
AB Neutrophilic inflammation has a key role in the pathophysiology of multiple chronic lung diseases. The formation of neutrophil extracellular traps (NETs) has emerged as a key mechanism of disease in neutrophilic lung diseases including asthma, COPD, cystic fibrosis and, most recently, bronchiectasis. NETs are large, web-like structures composed of DNA and anti-microbial proteins that are able to bind pathogens, prevent microbial dissemination and degrade bacterial virulence factors. The release of excess concentrations of proteases, antimicrobial proteins, DNA and histones, however, also leads to tissue damage, impaired mucociliary clearance, impaired bacterial killing and increased inflammation. A number of studies have linked airway NET formation with greater disease severity, increased exacerbations and overall worse disease outcomes across the spectrum of airway diseases. Treating neutrophilic inflammation has been challenging in chronic lung disease because of the delicate balance between reducing inflammation and increasing the risk of infections through immunosuppression. Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target. This review will discuss the relationship between NETs and the pathophysiology of cystic fibrosis, asthma, COPD and bronchiectasis, and explore the current and future development of NET-targeting therapies.NETs contribute to the pathophysiology of chronic lung disease. Immunomodulating therapies that may reduce inflammatory mediators and NET formation, without compromising bacterial clearance, offer a new treatment path for patients. https://bit.ly/3fyJC6I