Sputum neutrophil elastase and inhaled antibiotic response in bronchiectasis: a post-hoc analysis of the ORBIT-4 trial

<b>Introduction:</b> Strategies are needed to select bronchiectasis patients who will respond to inhaled antibiotic treatment. Neutrophil elastase (NE) activity in sputum can identify patients at higher risk of airway infection and exacerbations. We investigated whether higher NE measurements at baseline predicted responders to inhaled liposomal ciprofloxacin in ORBIT-4. <b>Methods:</b> Sputum samples from the ORBIT-4 trial were processed and tested using the NEATstik®-a lateral flow test detecting NE conc. from 0 (&lt;8 µg·mL-1 NE activity) to 10 (max NE). ORBIT-4 was a large phase 3 RCT investigating the efficacy of inhaled ciprofloxacin in bronchiectasis. <b>Results:</b> 178 patients had sputum samples available at baseline for NE measurement. The average age was 63.2 and 66.3% female. NE at baseline varied from 0 to 10, with 105 (59.0%) having the highest levels (8-10). A statistically significant relationship between NE and bacterial load (BL) was observed (p=0.01). A higher NE score at baseline was associated with significant reduction in PE frequency in those who were treated with inhaled ciprofloxacin compared to placebo (HR 0.53 95% CI 0.31-0.92, p=0.02) with no significant benefit in those with lower NE (p=0.22). A&nbsp;further reduction in PE frequency was seen in treated patients who had both an elevated NE score and PA BL (&gt;7LogCFU per g) (HR 0.47 95% CI 0.25-0.90, p=0.02). Patients with a high BL and a higher NE score at baseline were significantly more likely to have a prolonged time to first PE (HR 0.40 95% CI 0.21-0.77, p=0.006). <b>Conclusion:</b> Patients with elevated NE and BL may respond better to inhaled antibiotics. These biomarkers should be prospectively tested in RCT9s.