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Chronic Conditions in Older Adults and Susceptibility to Environmental Exposures

Chronic Conditions in Older Adults and Susceptibility to Environmental Exposures. Mark W. Frampton MD Pulmonary & Critical Care Division University of Rochester Medical Center. Questions About Susceptibility to Air Pollution in the Elderly. What are the conditions involved?

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Chronic Conditions in Older Adults and Susceptibility to Environmental Exposures

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  1. Chronic Conditions in Older Adults and Susceptibility to Environmental Exposures Mark W. Frampton MD Pulmonary & Critical Care Division University of Rochester Medical Center

  2. Questions About Susceptibility to Air Pollution in the Elderly • What are the conditions involved? • How does air pollution affect patients with these conditions? • Can air pollution cause these conditions?

  3. Diseases of Concern • Obstructive Lung Disease • Cardiovascular disease • Infection • Cancer • Others that haven’t been studied? • Obstructive sleep apnea • Pulmonary fibrosis • Chronic cough

  4. Obstructive Lung Diseases • Asthma • COPD, Chronic Bronchitis • Cystic Fibrosis • Smoking?

  5. The Normal Airway

  6. Mucosal Inflammation

  7. Increased Secretions

  8. The Airway in Asthma

  9. Spirometry Flow-Volume Loop Normal COPD

  10. PM Xenon Fractional Deposition 0.3 0.25 Diameter = 1 µm 0.2 NORMAL 0.15 0.1 0.05 0 SAD COPD Smoker Asthma Normal COPD Bennett et al., 1993, 2002 Kim et al., 1997 Dosimetry & Fate of Deposited PM

  11. Respiratory Deposition of UFP

  12. Cardiovascular Disease • Atherosclerosis • Coronary artery disease • Myocardial infarction • Congestive heart failure • Cardiac arrhythmias • Peripheral vascular disease • Diabetes • Pulmonary hypertension

  13. Increase in Atherosclerosis with 10 µg/m3 increase in PM2.5Künzli et al., EHP 2004

  14. Canine Myocardial Ischemia Model • Implantation of balloon occluder for coronary artery occlusion • 5 min occlusions with CAPs or Sham exposures. Wellenius et al., 2002

  15. Wellenius et al., 2002

  16. Endothelial Dysfunction in Atherosclerosis Ross et al., NEJM 1999

  17. Early Atherosclerosis Diaz et al., NEJM 1997

  18. How do inhaled particles cause effects in blood vessels?

  19. Science, 2005

  20. Does exposure to UFP alter endothelial function in the pulmonary circulation?

  21. Exposure to Carbon UFP • Count median diameter ~26 nm, GSD ~1.6 • 2 hrs by mouthpiece • Intermittent exercise

  22. Experimental Protocol Symptoms Phlebotomy Exhaled NO DLCO Spirometry Oximetry Resting HRV Flow-mediated dilatation = UFP or Air = -2 0 2 4 6 24 48

  23. Leukocyte Recruitment in Inflammation

  24. Pulmonary Diffusing Capacity for CO (DLCO):Sensitive to changes in pulmonary capillary blood volume

  25. Change in CO Diffusion Capacity After Exposureto 50 mg/m3 UFP

  26. Does exposure to UFP alter endothelial function in the systemic circulation?

  27. Systemic Endothelial Function:Flow-Mediated Vasodilatation

  28. After Exposure AM PM OONO- NO CD11a/ CD18 NO TF TF Fibrin & platelet deposition Monocyte Before Exposure Platelets Proposed Mechanisms for Vascular Effects of UFP

  29. Conclusions: PM Effects on Chronic Conditions in the Elderly • PM exacerbates obstructive lung disease • PM triggers cardiac events • PM may alter pulmonary & systemic endothelial function • PM may accelerate atherosclerosis • The key PM characteristics remain unknown • Likely other affected conditions

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