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PA-131 The contribution of neutrophils and their soluble markers to lung pathology in tuberculosis disease
  1. Basil Sambou1,
  2. Georgetta M Daffeh1,
  3. Caleb N Muefong1,2,
  4. Binta Sarr Kuyateh1,
  5. Abi Janet Riley1,
  6. Ensa Gitteh1,
  7. Ousman Secka1,
  8. Ulrich Schaible3,
  9. Christoph Leschczyk3,
  10. Jayne Sutherland1
  1. 1MRC Unit The Gambia at LSHTM, The Gambia
  2. 2University of Chicago, USA
  3. 3Research Centre Borstel, Leibniz Lung Centre, Germany


Background Tuberculosis is a leading infectious disease killer. It primarily affects the lung, accompanied by tissue damage from excessive host inflammation. Neutrophils are implicated as primary mediators of this tissue destruction. This study aims to access neutrophils and their soluble mediators in relation to TB-induced tissue damage.

Methods Fifty-three (53) patients with confirmed TB were recruited. Neutrophil numbers in sputum and blood were assessed using microscopy and automated counting. Soluble mediators were analysed in sputum and plasma by ELISA. Participants were classified as having mild (n=24) or severe (n=29) lung pathology at baseline based on a median chest X-ray Ralph score of 70%. Lung recovery was also assessed at 6 months of TB therapy with 14 participants classified as having good recovery and 15 having poor recovery based on overall change in Ralph score.

Results Plasma MMP9 levels at baseline were significantly higher in patients with severe [median (IQR) = 404548 (272166 - 465789) pg/ml] compared to mild [median (IQR) = 94461 (43194 – 168716) pg/ml] lung pathology (p=0.0277). Plasma MPO levels in both groups decreased significantly by week 2 (p=0.0287) and week 8 (p=0.0110) treatment respectively. Patients with severe lung pathology at baseline had significantly higher levels of circulating MPO compared to those with mild pathology [median (IQR) = 208913 (146125 - 239403) pg/ml and 106366 (69207 - 146633) pg/ml] (p=0.0432). No difference was seen in analytes between good and poor lung recovery patients.

Conclusion Severe lung pathology was associated with high plasma MMP-9 and plasma MPO at baseline. No difference was seen in good and poor lung recovery groups at 6 months but should be assessed at later time-points. Understanding how neutrophils and their associated protein markers drive lung pathology and subsequent long term post-TB lung disease could inform, whether and which HDT may support better treatment outcome.

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