Table 1.
Overview of translational evidence of NET formation in patients with COPD and asthma.
| Patient population (n) | Key translational findings using patient-derived samples | References |
|---|---|---|
| COPD (n = 6) | Increased NET production following LPS stimulation in peripheral blood-derived neutrophils from a small cohort of patients with stable COPD compared with healthy controls | (41) |
| COPD (n = 16) | Increased levels of NETs present in induced sputum samples from exacerbated COPD patients | (31) |
| COPD (n = 23) | Enhanced NET formation in induced sputum from stable COPD patients which correlated positively with airway neutrophil numbers and high concentrations of extracellular DNA | (29) |
| COPD (n = 44) | Abundant presence of sterile NETs in the sputum of patients with stable and exacerbated COPD that correlated with degree of airflow limitation [FEV1] and disease severity | (32) |
| COPD (n = 44) | Sputum NETs and airway neutrophils were inversely proportional to lung function and symptoms. Expression of PAD4 mRNA was upregulated in neutrophilic COPD | (42) |
| COPD (n = 99) | Increased sputum NET levels were associated with COPD severity (GOLD criteria), non-eosinophilic COPD exacerbations, reduced bacterial diversity and increased Haemophilus species | (45) |
| COPD (n = 12) | Enhanced NET induction in autologous blood and sputum neutrophils from COPD patients, this response was stabilized using the CXCR2 antagonist, AZD5069. This is the first mechanistic study to show an association specifically between CXCR2 signaling and NET stabilization in COPD ex vivo (Figures 1B–D) | (30) |
| Asthma (n = 20) | Accumulation of NETs and eosinophil extracellular traps (EETs) present in the bronchial biopsies of atopic asthmatics | (106) |
| Asthma (n = 94) | Raised levels of NETs detected in induced sputum derived from neutrophilic asthmatic relative to non-neutrophilic asthmatics that were inversely correlated to lung function and disease control | (42) |
| Asthma (n = 68) | Peripheral blood-derived neutrophils from severe asthmatics displayed greater NET production after CXCL8/IL-8 stimulation relative to cells from non-severe patients. These NETs induced airway epithelial damage and stimulated release of endogenous epithelial CXCL8/IL-8 production. | (33) |
| Asthma (n = 23) | Increased release of dsDNA following rhinovirus infection in vivo that was related to type-2 cytokine induction and exacerbation severity in asthmatics | (82) |