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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 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? • How does air pollution affect patients with these conditions? • Can air pollution cause these conditions?
Diseases of Concern • Obstructive Lung Disease • Cardiovascular disease • Infection • Cancer • Others that haven’t been studied? • Obstructive sleep apnea • Pulmonary fibrosis • Chronic cough
Obstructive Lung Diseases • Asthma • COPD, Chronic Bronchitis • Cystic Fibrosis • Smoking?
Spirometry Flow-Volume Loop Normal COPD
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
Cardiovascular Disease • Atherosclerosis • Coronary artery disease • Myocardial infarction • Congestive heart failure • Cardiac arrhythmias • Peripheral vascular disease • Diabetes • Pulmonary hypertension
Increase in Atherosclerosis with 10 µg/m3 increase in PM2.5Künzli et al., EHP 2004
Canine Myocardial Ischemia Model • Implantation of balloon occluder for coronary artery occlusion • 5 min occlusions with CAPs or Sham exposures. Wellenius et al., 2002
Endothelial Dysfunction in Atherosclerosis Ross et al., NEJM 1999
Early Atherosclerosis Diaz et al., NEJM 1997
Does exposure to UFP alter endothelial function in the pulmonary circulation?
Exposure to Carbon UFP • Count median diameter ~26 nm, GSD ~1.6 • 2 hrs by mouthpiece • Intermittent exercise
Experimental Protocol Symptoms Phlebotomy Exhaled NO DLCO Spirometry Oximetry Resting HRV Flow-mediated dilatation = UFP or Air = -2 0 2 4 6 24 48
Pulmonary Diffusing Capacity for CO (DLCO):Sensitive to changes in pulmonary capillary blood volume
Change in CO Diffusion Capacity After Exposureto 50 mg/m3 UFP
Does exposure to UFP alter endothelial function in the systemic circulation?
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
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