PA-404 Neutrophil associated markers in sputum to predict postTB lung impairment

<h3>Background</h3> Tuberculosis (TB) is the #1 bacterial killer worldwide. Despite of successful antibiotic treatment, exacerbated patients did not regain sufficient lung capacity and develop postTB lung disease (PTLD). We hypothesized, that neutrophils play an important role in disease exacerbation and associated marker can be used for early detection of PTLD. <h3>Methods</h3> 25 confirmed MDR-TB Patients were recruited, sputum samples were taken over 6 months and analyzed for neutrophil associated proteins by ELISA. TB severity was assessed at baseline and month 6 using spirometry (lung function) and x-ray (lung pathology). Patients were categorized in mild and severe diseased by using Ralph score (threshold 40 pts) or spirometry (threshold FVC&lt;0.85*LLN.FVC or gli.FEV1.zscore&lt;-2). <h3>Results</h3> 16 patients (64%) had a stable severe impairment in lung function and no improvement after 6 month was observed. In contrast, x-ray pathology was improving in 10 patients (40%) and remained stable severe in 10 patients (40%). Ralph scores were significantly higher in patients with impaired lung function. Neutrophil associated marker significantly declined under antibiotic treatment. Patients with stable severe impairment have significantly increased MMP8 sputum concentrations at baseline (p = 0.017) and increased concentrations of Calprotectin (p = 0.008), MPO (p = 0.034), ELA2 (p =0.031) and NGAL (p = 0.01) at week 2. In addition, Calprotectin (p = 0.005), MMP8 (p = 0.011) and NGAL (p = 0.03) concentrations were increased in males at month 4, while no sex differences in x-ray pathology was observed. <h3>Conclusion</h3> Early postTB lung impairment was associated with neutrophil proteins in acute TB and elucidate the impact of neutrophils on disease progression and immune pathology. These proteins will be further analyzed as targets for Host Directed Therapies to reduce oxidative stress, tissue degradation, as well as immune modulators to prevent PTLD. Funding: Funded by German Center for Infection Research