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Publicada porÁngel Navarro Marín Modificado hace 10 años
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R Rodriguez-Roisin UNIVERSITAT DE BARCELONA ANOMALÍAS VASCULARES PULMONARES EN LA EPOC MUY SEVERA (TRANSEPOC)
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Antecedentes Bio- y Fisiopatología Datos (TRANSEPOC) Contenido
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Antecedentes Bio- y Fisiopatología Datos (TRANSEPOC) Contenido
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...in patients with mild COPD the enlargement of the intimal layer in pulmonary muscular arteries is associated with a higher degree of V A /Q inequality, and that intimal thickening in small arteries seems to reduce the response of the pulmonary circulation to different oxygen concentrations. Barberà JA et al. AJRCCM 1994;149:423-9
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COPD: Bronchiolar & Pulmonary Vascular Abnormalities Intimal area (% total area) 60 50 40 30 20 10 0 0 203040 Bronchiolar inflammation score r = 0.65 p< 0.001
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Intimal area, % total 0 10 20 30 40 NSm Sm COPD * COPD: Pulmonary Arteries Morphometry * Peinado VI et al. AJP 1998;274:L908-13
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COPD: Endothelial Vascular Relaxation Adenosine Diphosphate, log [M] -10- 9- 8- 7- 6 -5- 4 -100 -80 -60 -40 -20 0 Never-Smokers Smokers COPD * Peinado VI et al. AJP 1998;274:L908-13 Maximal Relaxation (% Contraction to LP)
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Intimal area (% total area) 182124273033 50 60 70 80 90 NSm Sm GOLD 1 & GOLD 2 Maximal relaxation to ADP (% Contraction to PE) COPD: Endothelium-Dependent Relaxation Peinado VI et al. AJP 1998;274:L908-13
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COPD: Lymphocytic Infiltrate in Pulmonary Arteries NSmSm COPD 0 100 200 300 400 Cells/mm 2 CD8 + * * Peinado VI et al. AJRCCM 1999;159:1605-11 0 100 200 300 400 Cells/mm 2 CD4 + NSmSm COPD 0 0.5 1.0 1.5 2.0 2.5 CD4/CD8 ratio CD4 + /CD8 + * NSmSm COPD *
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Leukocytes, cells/mm 2 02004006008001000 Maximal relaxation to ADP, % 20 40 60 80 100 120 r = - 0.38 p < 0.05 Peinado VI et al. AJRCCM 1999;159:1605-11 COPD: Lymphocytic Infiltrate in Pulmonary Arteries
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Band intensity 0 30 60 90 120 150 Sm COPD: eNOS Expression in Pulmonary Arteries NSm Barberà JA et al. AJRCCM 2001;164:709-13 COPD 132 Kd *
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COPD Never-Smoker Severe Emphysema Santos S et al. AJRCCM 2003;167:1250-6 COPD: VEGF Expression in Pulmonary Arteries
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Non-SmokersSmokers COPD PULMONARY VASCULAR REACTIVITY INTIMAL THICKENING LYMPHOCYTIC INFILTRATE DECREASED eNOS & INCREASED VEGF COPD: Spectrum of Pulmonary Vascular Abnormalities
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Antecedentes Bio- y Fisiopatología Datos (TRANSEPOC) Contenido
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0 0.30 0.50 0.70 0.90 1.10 1.30 1.50 Grades 1234 LOG SDQ & LOG SDV Rodríguez-Roisin R et al. JAP 2009;106:1902-8 GOLD: Ventilation-Perfusion Imbalance n, 150
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Never-SmokerGOLD-4 Estépar RSJ et al. AJRCCM 2013;188:231-9
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CIGARETTE SMOKE INFLAMMATION Pulmonary Artery CELL PROLIFERATION ENDOTHELIAL DYSFUNCTION COPD: Pulmonary Vascular Abnormalities PULMONARY HYPERTENSION HYPOXEMIA Peinado VI et al. Chest 2008;134:308-14 VASCULAR REMODELLING INTIMAL THICKENING Vascular Tone
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Non-SmokersSmokers COPD PULMONARY VASCULAR REACTIVITY INTIMAL THICKENING LYMPHOCYTIC INFILTRATE DECREASED eNOS & INCREASED VEGF COPD: Spectrum of Pulmonary Vascular Abnormalities What About GOLD-3 & GOLD-4?
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Antecedentes Bio- y Fisiopatología Datos (TRANSEPOC) Contenido
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TRANSEPOC: General Characteristics Characteristics n, 17 Mean±SDRange Age, yrs56±4(49-63) Pack-years44±28(10-90) BMI, kg.m -2 26±4(18-34) 6MWT, m322±96(151-520) mMRC4±1(3-4) BODE Index (0 –10)7±2(5-10) Peinado VI et al. JHLT 2013;32:1262–69
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VARIABLESMean±SDRange FEV 1 (% predicted)23±6(13-34) FEV 1 /FVC0.29±0.08(0.19-0.48) FRC (% predicted)210±73(151-436) RV (% predicted)281±81(172-470) TLC (% predicted)131±28(94-220) IC/TLC ratio0.20±0.06(0.09-0.33) RV/TLC (%)71±6(63-85) DL CO (% predicted)37±15(13-73) TRANSEPOC: Lung Function Tests Peinado VI et al. JHLT 2013;32:1262–69
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AMBIENT AIR100% O 2 p values PaO 2, mmHg59±9 539±69 <0.001 PaCO 2, mmHg46±751±10 <0.001 Log SDQ (≤ 0.60)0.9±0.21.1±0.2 <0.001 Log SDV (≤ 0.65)1.1±0.21.1±0.2NS Dead Space, %35±1039±7<0.05 TRANSEPOC: Pulmonary Gas Exchange Peinado VI et al. JHLT 2013;32:1262–69
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ΔLog SDQ TRANSCOPD 0.20 ± 0.10 HEALTHY Individuals (n, 5) 0.17 ± 0.15 Reactive COPD -1 & -2 (> 0.41) (n, 11) 0.57 ± 0.13 Non-Reactive COPD -1 & -2 (≤ 0.41) (n, 9) 0.25 ± 0.12 TRANSEPOC: Ventilation-Perfusion Response to 100% Oxygen Peinado VI et al. JHLT 2013;32:1262–69
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AMBIENT AIR100% OXYGENp values Q T, L.min -1 4.8±0.84.5±0.6<0.01 PAP, mmHg23±519±5<0.01 PVR, mmHg.L -1.min -1 301±96251±85<0.001 TRANSEPOC: Pulmonary Hemodynamics Peinado VI et al. JHLT 2013;32:1262–69
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TRANSEPOC: Emphysema Subjective Score (76 ± 17%; 47-95%)
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TRANSEPOC: Lung Morphometry TOTAL PATHOLOGICAL Score 76 ± 27 EMPHYSEMA Score 62 ± 17 Mean Linear Intercept 0.36 ± 0.09 Peinado VI et al. JHLT 2013;32:1262–69
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Endothelial Dysfunction Intimal Thickening (Remodelling) PAP CIGARETTE SMOKE eNOS SMCs Proliferation INFLAMMATION PRODUCTS HPV EC V A /Q Mismatch INFLAMMATION VEGF HYPOXEMIA Shear Stress COPD: Pulmonary Vascular Abnormalities Peinado VI et al. Chest 2008;134:308-14
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Peinado VI et al. JHLT 2013;32:1262–69
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CHEST 2012; 142:1654-8
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Intima area, % total 0 10 20 30 40 NSm Sm * TRANSEPOC: Pulmonary Arteries Morphometry * COPD LT Peinado VI et al. JHLT 2013;32:1262–69
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TRANSEPOC: Lymphocytic Infiltrate in Pulmonary Arteries NSmSm 0 100 200 300 400 Cells/mm 2 CD8 + * * 0 0.5 1.0 1.5 2.0 2.5 CD4/CD8 ratio CD4 + /CD8 + * NSmSmCOPD * LT * * Peinado VI et al. JHLT 2013;32:1262–69
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Contraction to Hypoxia, % KCl 0 5 10 15 20 Sm COPD * * LT TRANSEPOC: Pulmonary Vascular Reactivity Peinado VI et al. JHLT 2013;32:1262–69
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0510152025 100 200 300 400 500 600 PVR, dyn.s.cm -5 TRANSEPOC: PVR & Hypoxic Vascular Reactivity RESPONSE TO HYPOXIA, % KCl r = 0.60 p < 0.02 Peinado VI et al. JHLT 2013;32:1262–69
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0510152025 PAP Changes, mmHg 2 0 -2 -4 -6 -8 -10 -12 r = 0.54 p < 0.04 TRANSEPOC: Oxygen-Induced Changes in PAP & Hypoxic Vascular Reactivity RESPONSE TO HYPOXIA, % KCl
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El enfisema pulmonar es severo pero la hipertensión pulmonar (HP) es discreta La morfometría vascular pulmonar está relativamente bien conservada La reactividad vascular hipóxica y la relajación endotelial arterial son discretas Hay un intenso infiltrado inflamatorio en la adventicia vascular Hallazgos principales
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Es probable que el enfisema pulmonar constituya el mayor determinante de la HP (discreta) de estos pacientes con EPOC muy severa Sorprenden las mínimas diferencias en las anomalías vasculares pulmonares entre estos pacientes con EPOC muy severa y las observadas previamente en no fumadores con espirometría normal, en contraste con las diferencias muy superiores observadas entre no fumadores y fumadores con espirometría normal o pacientes con EPOC leve-moderada Conclusiones
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GOLD 2 GOLD 3 GOLD 4 DISEASE PROGRESSION IN COPD Decramer M & Cooper C. Thorax 2010;65:837-41 50 ml/yr 30 ml/yr 35 ± 1 ml/yr 25 ± 2 ml/yr 33 ± 1 ml/yr Vestbo J et al. NEJM 2011;365:1184-92
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