Recommended
More Related Content
What's hot
What's hot (20)
Similar to 03 BRN Research Forum Bronquiectasias. Parte III por Oriol Sibila
Similar to 03 BRN Research Forum Bronquiectasias. Parte III por Oriol Sibila (20)
More from brnmomentum
More from brnmomentum (20)
Recently uploaded
Recently uploaded (20)
03 BRN Research Forum Bronquiectasias. Parte III por Oriol Sibila
- 1. USO DE BIOMARCADORES EN LA CONSULTA DE BRONQUIECTASIAS Oriol Sibila Servei de Pneumologia Hospital Clínic @OSibila
- 3. Polverino E et al, Eur Respir J 2017 ✓ Conditional recomendation ✓ Low (or very low) quality of evidence ✓ No licensed treatment
- 4. RECENT RANDOMISED CLINICAL TRIALS IN BRONCHIECTASIS
- 5. Sibila O, Eur Respir J 2022 Response to treatment: - Changes in QoL above MCID -Changes in FEV1 of ≥ 100 ml -Abcense of Exacerbations Endpoints: -QoL -FEV1 -Exacerbations n=461 n=83 n=538
- 6. Sibila O, Eur Respir J 2022 -Mannitol RCT
- 7. Sibila O, Eur Respir J 2022 -Mannitol RCT FEV1 Responders (≥ 100 ml)
- 8. Sibila O, Eur Respir J 2022 -Mannitol RCT QOL Responders (↓SGRQ ≥ 4 points)
- 9. Sibila O, Eur Respir J 2022 -Mannitol RCT No exacerbation ≥1 exacerbation
- 10. Sibila O, Eur Respir J 2022 -Azythromicin RCT
- 11. Sibila O, Eur Respir J 2022 -Aztreonam RCT
- 12. Clinical predictors to treatment response Sibila O, Eur Respir J 2022
- 14. N=1000 patients Follow-up: 36 months BRIDGE project Bronchiectasis Research Integrating Data with Genomics and Endotyping
- 15. 3.1 Primary Objective -To determine molecular endotypes of bronchiectasis which can guide response to treatment. 3.2 Secondary Objectives -To determine and validate candidate biomarkers to use in stratified medicine -To determine molecular endotypes of stable bronchiectasis -To determine the causes and inflammatory profiles of bronchiectasis exacerbations -To perform in-vivo or in-vitro proof of concept studies using phenotypic data to identify patient populations likely to benefit in future randomized controlled trials BRIDGE project Bronchiectasis Research Integrating Data with Genomics and Endotyping
- 16. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 17. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 18. Denney L, Biomedical Journal 2018 MUCINS
- 19. Science 2009 Nature 2014
- 20. Sibila O et al, Respirology 2016
- 21. Ramsey K et al, Am J Respir Crit Care Med 2021
- 22. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 23. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 24. Luppeti A, Lancet Infect Dis 2003 Lactoferrin Lysozime LL-37 SLPI Antimicrobial Peptides (AMPs):
- 25. Multicenter 1 year follow-up LL-37 Lysozime Lactoferrine SLPI Sputum and serum Sibila O et al, Thorax. 2019; 74(9):835-842 N o n -in fe c te d 0 1 0 0 2 0 0 3 0 0 4 0 0 P .a e ru g in o s a O th e r p a th o g e n s S p u tu m la c t o f e r r in ( µ g /m l) p=0.04 LL-37 Lactoferrin SLPI
- 26. SLPI (Secretory Leukocyte Protease Inhibitor) Sibila O et al, Thorax. 2019; 74(9):835-842
- 27. Perea L et al, Chest 2021
- 28. Perea L et al, Chest 2021
- 29. Perea L et al, Chest 2021
- 30. Perea L et al, submitted
- 32. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 33. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 34. Int J Mol Sci 2019 NEUTROPHIL ELASTASE
- 35. Am J Respir Crit Care Med 2017
- 36. Am J Respir Crit Care Med 2017
- 37. Eur Respir J 2019
- 38. Eur Respir J 2019 >6 Exacerbations
- 39. Chalmers JD et al, N Eng J Med 2020 n=256
- 40. Chalmers JD et al, N Eng J Med 2020
- 41. Int J Mol Sci 2021
- 42. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 43. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 44. Neutrophil Extracellular Traps (NETs) Dicker AJ, J Allergy Clin Immunol 2018
- 45. Keir HR et al, Lancet Resp Med 2021
- 46. Keir HR et al, Lancet Resp Med 2021 p<0.001
- 47. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 48. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 49. Chalmers JD et al, Am J Respir Crit Care Med 2012 BACTERIAL LOAD
- 50. Am J Respir Crit Care Med 2019 Airway Bacterial Load: -Low (<105 ufc/g) -Moderate (105-106) -High (>106)
- 51. 1) BL is associated worse QOL and severity of disease Sibila O et al, AJRCCM 2019
- 52. Log 10 cfu/g B a s e l i n e A f t e r t r e a t m e n t F o l l o w - u p 0 1 2 3 4 5 6 7 8 9 1 0 H ig h M o d e ra te L o w 1 3 5 7 1 4 0 1 2 3 4 5 6 7 8 9 1 0 Log 10 cfu/g Day from enrolment 2) Bacterial load is an stable trait Sibila O et al, AJRCCM 2019
- 53. Sibila O et al, AJRCCM 2019 3) Response to inhaled aztreonam was evident only in patients with high BL in the AIR-BX studies
- 54. Crichton M, et al. Eur Respir J 2020
- 56. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 57. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 58. EOSINOPHILS J Allergy Clin Immunol 2020 Lancet Resp Med 2018 GOLD 2022
- 59. RIBRON REGISTRY N=906 THRESHOLD 100 c/ML Wang et al, Int J Environ Res Public Health 2021
- 60. 22,6% >300 c/mL Shoemark et al, Am J Respir Crit Care Med 2022 (in press)
- 61. Shoemark et al, Am J Respir Crit Care Med 2022 (in press)
- 62. Shoemark et al, Am J Respir Crit Care Med 2022 (in press)
- 63. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 64. Biomarkers in Bronchiectasis • Mucins • Antimicrobial peptides • Neutrophil elastasa • NETS • Bacterial load • Eosinophils • VOCs
- 65. . .. . . . . . . . . . . . : .. . . . . . . . . . : .. . . . . . . . . . : Volatile Organic Compounds (VOCs) E-nose
- 66. Resp Med 2014 Am J Respir Crit Care Med 2009
- 67. Resp Med 2018
- 68. Oliveira L et al, Clin Chem Acta 2021 Control (n=9) Bronchiectasis (n=13) Bronchiectasis with P.aeruginosa (n=12)
- 69. -Gas Chromatography-Mass Spectometry (GC-MS) Oliveira L et al, Clin Chem Acta 2021
- 70. ¿mucoactive treatments? ¿inhaled antibiotics? ¿macrolides? ¿antiinflamatories therapies? CONCLUSIONS Mucins AMP, Bacterial load NETs Eosiophils (ICS??) Neutrophil Elastase (Brensocatib?)
- 71. ACKNOWLEDGMENTS University of Dundee (Scotland, UK) -James D Chalmers -Amelia Shoemark -Holly R Keir University of Milano (Italy) -Stefano Aliberti -Martina Oriano -Andrea Gramegna Hospital Clínic, IDIBAPS -Belen Solarat -Silvia Morales -Lídia Perea -Rosa Faner -Tamara Garcia -Núria Mendoza -Alvar Agustí Hospital Sant Pau, IIB -Ana Rodrigo-Troyano -Guillermo Suarez-Cuartin -Elisabet Cantó -Silvia Vidal