Neutrophil extracellular traps are associated with inflammation in chronic airway disease

Abstract Background and objective Neutrophil extracellular traps ( NETs ) are web‐like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NET osis. Persistence of NETs can be pro‐inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD , and the relationship of NETs with inflammatory phenotype and disease severity. Methods Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (e DNA ) was quantified by PicoGreen. LL ‐37, α‐defensins1–3, NE , IL ‐1β and CXCL 8 were quantified by ELISA . PAD 4 and NLRP 3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy. Results Sputum e DNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of e DNA and NET components were significantly higher in neutrophilic versus non‐neutrophilic asthma and COPD . NETs were clearly visualized in sputum smears. PAD 4 m RNA was upregulated in neutrophilic COPD . The level of e DNA was higher in severe asthma. High e DNA levels were associated with heightened innate immune responses, including elevated CXCL 8 and IL ‐1β, and NLRP 3 gene expression in both COPD and asthma. Antimicrobial proteins and e DNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms. Conclusion NETs are present in the airways of subjects with asthma and COPD . Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease.