Targeted DNase treatment of obstructive lung disease: a pilot randomised controlled trial.

BACKGROUND: Sputum extracellular DNA (eDNA) is associated with disease severity in asthma and COPD and therefore emerging as a potential therapeutic target. The aim of this study was to investigate the effect of 10 days of recombinant human DNase (rhDNase) treatment of eDNA-high asthma and COPD on sputum eDNA levels, neutrophil-related inflammation, lung function and symptoms. METHODS: Adults with asthma (n=80) or COPD (n=66) were screened for the presence of high (>20 µg·mL) sputum eDNA and those eligible (n=18 asthma, n=17 COPD) were randomised to a two-period crossover controlled trial consisting of daily nebulised rhDNase (2.5 mg/2.5 mL) or placebo (5 mL 0.9% saline) for 10 days, with a 2-week washout period. The primary outcome was sputum eDNA, and secondary outcomes included sputum neutrophil extracellular trap (NET)-related biomarkers, inflammatory cell counts, lung function and respiratory symptoms. RESULTS: At screening, high eDNA was associated with significantly higher sputum total cell count, sputum colour score and inflammation (HNP1-3, LL-37 and interleukin-1β) in both asthma and COPD compared to low eDNA groups. In asthma, participants with high eDNA were older and had poorer lung function and asthma control compared to low eDNA. Administration of nebulised rhDNase significantly reduced sputum eDNA levels in both asthma (median (Q1-Q3) Pre: 48.4 (22.1-74.1); Post: 17.0 (5.0-31.0) µg·mL; p=0.022) and COPD (median (Q1-Q3) Pre: 39.3 (36.7-55.6); Post: 25.4 (11.3-38.6) µg·mL; p=0.044) compared to placebo. Symptoms, lung function and NET biomarkers remained unchanged. In asthma, there was a reduction in banded blood neutrophils (3.2 (0-7.7) to 0.0 (0.0-1.5); p=0.044). CONCLUSION: Targeted rhDNase treatment for 10 days effectively reduced sputum eDNA in eDNA-high asthma and COPD.