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- Lung

- Lung. The MESA Lung Studies. R Graham Barr, MD DrPH Departments of Medicine and Epidemiology Columbia University Medical Center. Outline. MESA COPD and MESA Lung II Scientific Rationale Recruitment Preliminary Findings MESA Lung SHARe MESA Lung Fibrosis.

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- Lung

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  1. -Lung The MESA Lung Studies R Graham Barr, MD DrPH Departments of Medicine and Epidemiology Columbia University Medical Center

  2. Outline • MESA COPD and MESA Lung II • Scientific Rationale • Recruitment • Preliminary Findings • MESA Lung SHARe • MESA Lung Fibrosis

  3. CLRD Deaths Surpassed Stroke in 2008 http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_02.pdf, 2010

  4. Chronic Lower Respiratory Disease EMPHYSEMA CHRONIC BRONCHITIS COPD CHRONIC OBSTRUCTIVE PULMONARY DISEASE ASTHMA

  5. Endothelial Hypothesis of Emphysema Smoking Endothelial apoptosis and dysfunction Microvascular damage Systemic circulation Alveolar destruction (%emphysema) Airflow obstruction Pulmonary circulation ↓ Pulmonary blood flow ↓LV-EDV ↓SV

  6. - Lung % Emphysema and Stroke Volume Current Smokers Former Smokers Never Smokers P<0.001 (linear) P<0.001 (linear) P<0.001 (linear) Stroke Volume (ml) CT percent emphysema • Solid dots = Stroke volume; thin lines = 95% CI Adjusted for age, sex, race/ethnicity, education, smoking status, packyears, cigars, BSA, height, diabetes, fasting plasma glucose, hypertension, systolic and diastolic blood pressure, CRP, scanner type and mAs. • P-interaction with smoking status <0.001 Barr, NEJM, 2010

  7. - COPD Recruitment MESA Lung II (Spirometry)  Selection broadened to include all those undergoing MRI MESA COPD – completed (n~325; ~200 in MESA)

  8. - COPD Pulmonary Vascular Damage • Endothelial microparticles (≤1.5 µm) • “Apoptotic”: CD31+ (PECAM-1), CD42b-

  9. - COPD EMPs and COPD Severity Mean differences in EMPs adjusted for 1) age, sex, race/ethnicity in addition to 2) smoking status and packyears

  10. - COPD Other Potential Mechanisms • Subclinical cor pulmonale (low LV-EDP) • Pulmonary veins on MRI • Myocardial fibrosis • T1 mapping • Diastolic function measures • Increased intra-thoracic pressure • Hyperinflation on CT and plethysmography

  11. MESA Lung SHARe • GWAS for percent emphysema (cardiac CT) • Pan-lobular emphysema • Basilar predominance • α-1 anti-trypsin deficiency Gough, Post Grad Med, 1965 Erikkson, Acta Medica Scandinavia, 1965 Gooptu, PNAS, 2000

  12. MESA Lung SHARe (n~8,000) • Percent emphysema-950 • MAN1C1 (Chr 1) • Upper-lower ratio-950 • MAN2B1 (Chr 19) • 2 of 3 human isoforms that modify α-mannosidase • Degrades α1-antitrypsin

  13. MESA Lung Fibrosis • Interstitial lung disease is leading reason for lung transplantation • R01 on subclinical lung fibrosis on CT • Validation of CT measures in 100 MESA participants at Columbia • Cardiopulmonary exercise test • Body plethysmography • MESA Lung spirometry and CT (n~40)

  14. - COPD Thank you!!! University of Vermont Margaret Doyle Russell Tracy University of Iowa Eric Hoffman Heather Baumhauer Northwestern University Kiang Liu James Carr UCLA Karol Watson The MESA COPD Study Columbia University R Graham Barr Martin Prince Daichi Shimbo Corey Ventetuolo Johns Hopkins University Joao Lima David Bluemke Chia Liu Wendy Post NIH/NHLBI R01-HL093081, RC1-HL077612, RC1-HL100543

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