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 NormalCOPD

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

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/m 3 increase in PM 2.5 Künzli 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

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?

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

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

24. Leukocyte Recruitment in Inflammation

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

26. Change in CO Diffusion Capacity After Exposure to 50 mg/m 3 UFP

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

28. Systemic Endothelial Function: Flow-Mediated Vasodilatation

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

30. 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