RESPIRATORY INFECTIONS, IMMUNITY, AND HEMOSTASIS IN AGING

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Acute viral respiratory tract infection (ARTI), especially that caused by infection with respiratory syncytial virus (RSV) and influenza, causes excess rates of hospitalization and increased mortality in older persons. In addition, ARTI is a common cause of involuntary immobility in frail elderly, often setting into motion a cascade of events resulting in substantial disability, functional decline, and subsequent loss of independence. The Rochester AREA Pepper Center (RAPC) has begun to define the epidemiology, clinical characteristics, and impact on functional state of these common illnesses, focusing on the frail elderly in the setting of adult day centers and in long term care facilities as the most vulnerable populations of older persons. A postulated linkage between acute infection and cardiovascular events is supported by a growing body of literature. The common linkage between these two important phenomena may be alterations in the hemostatic system related to inflammatory and immunologic responses to viral infection. A better understanding of the immune response to infection in older persons, and its relationship with the hemostatic system may lead to a number of specific interventions including targeted immunization, anticoagulation strategies, or remediation of defects in the immune system by improved nutrition. The Intervention Development studies proposed have the following aims: 1. Define the heterogenicity of the immune response as a function of age and define potentially reversible aspects. 2. Determine whether immune biomarkers may be predictors of more severe ARTI. 3. Evaluate the host response of older persons to natural infection with influenza an RSF. 4. Identify hemostatic parameters associated with risk of vascular events in the same cohort of frail elderly. 5. Investigate the reaction between acute viral infection and a prothrombotic state. 6. Trial immunomodulatory interventions. 7. Evaluate the role of low intensity anticoagulation. Controlled clinical trials have been designed. Testing will include viral diagnostic methods, measures of cellular and humoral immunity, hemostatic determinations, and geriatric functional assessment.