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R Rodríguez-Roisin, MD

Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra. Le ricordiamo che questo materiale è di proprietà dell’autore e fornito come supporto didattico per uso personale. Universitat de Barcelona.

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R Rodríguez-Roisin, MD

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  1. Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra.Le ricordiamo che questo materiale è di proprietà dell’autore e fornito come supporto didattico per uso personale.

  2. Universitat de Barcelona INCREASED PERIPHERAL NEUTROPHIL STIFFNESS IN COPD: IS IT RELEVANT? R Rodríguez-Roisin, MD

  3. AGENDA • Background • Approaches • Data • Implications

  4. COPD & PULMONARY INFLAMMATION Barnes, PJ. NEJM 2000;343:269-80

  5. SPUTUM NEUTROPHILS IN STABLE COPD WYE8N41 - Global Slide Kit Rytllä P et al. ERJ 2007:28:1163-9

  6. NEUTROPHILS & BRONCHIAL GLANDS IN STABLE COPD This photomicrograph shows neutrophil infiltration (red) in the bronchial glands of a patient with symptoms of chronic bronchitis and chronic airflow obstruction. Bronchial Gland, Neutrophil, Obstruction 7 Saetta M et al. AJRCCM 1997;156:1633-9

  7. NATURE OF SMALL AIRWAY OBSTRUCTION IN COPD Hogg JC et al. NEJM 2004;350:2645-53

  8. SYSTEMIC EFFECTS & COPD Agustí AGN et al. ERJ 2003;21:347-60

  9. NEUTROPHIL RESPONSE IN COPD Noguera A et al. Thorax 2001;56:432-7

  10. AGENDA • Background • Approaches • Data • Implications

  11. APPROACHES Induced Sputum Bronchoalveolar Lavage Bronchial Biopsy Lung Tissue Peripheral Blood

  12. LUNG NEUTROPHIL RETENTION In the uninflamed lung, most neutrophils must become elongated to pass through the capillary bed into the venules. Inflammatoy stimuli induce neutrophils to become stiffer and less able to be deformable… Endothelium Neutrophil 2-15 µm Capillary 6-8 µm Neutrophil Alveolar lumen Epithelium Cell rheology Cell adhesion signalling Neutrophil sequestration within lungs Doerschuk CM. AJRCCM 1999;159:1693-5

  13. LUNG NEUTROPHIL RETENTION …This retention is probably due to the process of deformation that neutrophils undergo when entering microcapillaries, which is dependent on neutrophil mechanical properties. The retention of neutrophils in microcapillaries is known to increase with neutrophil stiffness... Worthen, GS et al. Science 1989;245:183-6

  14. ATOMIC FORCE MICROSCOPE TECHNIQUE Extraction of 4 ml of peripheral venous blood Isolation of neutrophils Atomic Force Microscopy (AFM) Fotodiode Laser beam Lens d Cantilever 40 µm Neutrophil AFM measurements Phase contrast image Coverslip

  15. AGENDA • Background • Approaches • Data • Implications

  16. Peripheral blood neutrophil stiffness could be increased in parallel to the spirometric severity of COPD and the underlying structural derangement into the lungs This increased neutrophil stiffness could decrease after bilateral pulmonary transplantation HYPOTHESIS

  17. PERIPHERAL NEUTROPHIL STIFFNESS & COPD

  18. PERIPHERAL NEUTROPHIL STIFFNESS & COPD: AFTER LUNG TRANSPLANT (LT)

  19. PERIPHERAL NEUTROPHIL STIFFNESS & COPD

  20. PERIPHERAL NEUTROPHIL STIFFNESS & COPD

  21. 1. Compared with healthy nonsmokers peripheral blood neutrophil stiffness is increased not only in COPD patients across the spectrum of all spirometric grades but also in smokers with normal lung function. SUMMARY (1)

  22. SUMMARY (2) Increased peripheral neutrophil stiffness is associated with the presence of symptoms and with lung function abnormalities (spirometry and gas exchange). After lung transplantation increased peripheral neutrophil stiffness normalizes without differences with healthy nonsmokers.

  23. Increased peripheral neutrophil stiffness across the different COPD grades reflects both impact and severity of disease. Moreover, increased neutrophil stiffness precedes COPD development. Its reduction to normalcy after lung transplantation indicates that it is primarily modulated by underlying lung architectural pathology, without excluding a reduction of systemic inflammation CONCLUSIONS

  24. PERIPHERAL NEUTROPHIL STIFFNESS & COPD EXACERBATIONS RECURRENT EXACERBATIONS NON-RECURRENT EXACERBATIONS 104 104 NS p < 0.05 Cell Stiffness, Pa 103 103 102 102 Admission Convalescence Admission Recurrence

  25. PERIPHERAL NEUTROPHIL STIFFNESS & COPD EXACERBATIONS 8.5 r = 0.60 p < 0.05 8.0 7.5 7.0 ADO Index 6.5 6.0 5.5 5.0 102 103 104 Cell Stiffness, Pa

  26. AGENDA • Background • Approaches • Data • Implications

  27. ROFLUMILAST & INFLAMMATORY CELLS IN STABLE COPD Grootendorst DC et al. Thorax 2007;62:1081-7

  28. NOVEL CXCR2 ANTAGONIST & NEUTROPHILIA INHIBITION Holz Y et al. ERJ 2010;35:564-70

  29. Universitat de Barcelona ACKNOWLEDGEMENTS Almendros, Isaac (IDIBAPS) Hernández, Lisbeth (FCRB) Navajas, Daniel (UB) Roman, Antonio (HVH)

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