Project Grant R56ES035767

PM2.5 METALS, OXIDATIVE POTENTIAL, EXPOSURE, AND RISK ASSESSMENT (PM OPERA): A NATIONAL MORBIDITY AND MORTALITY STUDY - PROJECT SUMMARY OUTDOOR FINE PARTICULATE AIR POLLUTION (PM2.5, PARTICLES WITH AERODYNAMIC DIAMETER < 2.5 M) IS A LEADING CAUSE OF GLOBAL MORBIDITY AND MORTALITY, CONTRIBUTING TO MILLIONS OF PREMATURE DEATHS EACH YEAR. CLIMATE CHANGE WILL WORSEN THE BURDEN OF DISEASE FROM PM2.5 IN THE COMING DECADES, WITH SEVERE EFFECTS FELT BY THOSE OF LOW SOCIOECONOMIC STATUS AND FROM UNDERREPRESENTED RACIAL AND ETHNIC GROUPS. LITTLE IS KNOWN ABOUT THE EXTENT TO WHICH DIFFERENT US POPULATIONS MAY EXPERIENCE "DIFFERENT KINDS OF PARTICLES" WITH RESPECT TO PM2.5 COMPOSITION AND OVERALL TOXICITY. RECENT RESEARCH SUGGESTS THAT THE COMBINED TRANSITION METAL AND SULFUR CONTENT OF PM2.5 MAY INFLUENCE THE RESPIRATORY AND CARDIOVASCULAR HEALTH RISKS THAT RESULT FROM ACUTE AND CHRONIC EXPOSURE. OXIDATIVE STRESS IS AN IMPORTANT MECHANISM LINKED TO THE CARDIORESPIRATORY HEALTH EFFECTS OF PM2.5 AND SEVERAL RECENT STUDIES HAVE INCORPORATED MEASURES OF PM2.5 OXIDATIVE POTENTIAL (A MEASURE OF THE ABILITY OF PARTICLES TO PROMOTE OXIDATIVE STRESS IN CELLS AND TISSUES) AS A COMPLEMENTARY METRIC TO PM2.5 MASS. IMPORTANTLY, SEVERAL OF THESE STUDIES HAVE NOTED STRONGER ASSOCIATIONS BETWEEN OUTDOOR PM2.5 MASS CONCENTRATIONS AND BOTH ACUTE AND CHRONIC HEALTH OUTCOMES WHEN THE PM2.5 OXIDATIVE POTENTIAL WAS ELEVATED. WE HYPOTHESIZE THAT PARTICLE ACIDITY INCREASES THE BIOAVAILABILITY OF PM METALS, ALLOWING THEM TO PARTICIPATE IN REDOX REACTIONS THAT CONTRIBUTE TO OXIDATIVE STRESS AND POTENTIAL ADVERSE CARDIOVASCULAR AND RESPIRATORY HEALTH OUTCOMES. THE OBJECTIVE OF THIS RESEARCH IS TO DETERMINE HOW SPATIAL AND TEMPORAL VARIATIONS IN PM2.5 COMPOSITION AND OXIDATIVE POTENTIAL MAY MODIFY THE STRENGTH OF ASSOCIATIONS BETWEEN PM2.5 MASS CONCENTRATIONS AND CARDIORESPIRATORY MORBIDITY/MORTALITY. WE WILL DEPLOY A LOW-COST MEASUREMENT NETWORK TO QUANTIFY PM2.5 OXIDATIVE POTENTIAL ON A NATIONAL SCALE. COLLECTED SAMPLES WILL BE ANALYZED FOR TRACE ELEMENTS AND OXIDATIVE POTENTIAL (AIM 1). WITH THESE DATA WE WILL CONDUCT A NATIONAL-SCALE TIME-STRATIFIED CASE-CROSSOVER STUDY OF DAILY VARIATIONS IN OUTDOOR PM2.5 MASS CONCENTRATIONS AND ACUTE CARDIORESPIRATORY MORBIDITY AMONG MEDICARE ENROLLEES (AIM 2). SPECIFICALLY, THIS ANALYSIS WILL EVALUATE HOW MONTHLY VARIATIONS IN PM2.5 COMPONENTS AND OXIDATIVE POTENTIAL ACROSS THE US MODIFY THE STRENGTH OF ASSOCIATIONS BETWEEN DAY-TO-DAY CHANGES PM2.5 MASS CONCENTRATIONS AND ACUTE HEALTH OUTCOMES (ACUTE MYOCARDIAL INFARCTION, ISCHEMIC HEART DISEASE, CONGESTIVE HEART FAILURE, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND ASTHMA) AMONG POTENTIALLY SENSITIVE SUBSETS OF THE US POPULATION. FINALLY, WE WILL CONDUCT A COHORT STUDY IN THE MEDICARE COHORT (AIM 3) TO EVALUATE HOW SPATIAL VARIATIONS IN ANNUAL AVERAGE ESTIMATES OF PM2.5 COMPONENTS AND OXIDATIVE POTENTIAL ACROSS THE US MODIFY THE STRENGTH OF ASSOCIATIONS BETWEEN YEARLY CHANGES PM2.5 MASS CONCENTRATIONS AND CHRONIC HEALTH OUTCOMES AMONG POTENTIALLY SENSITIVE SUBSETS OF THE US POPULATION. WE WILL ALSO ESTIMATE THE SHAPES OF CONCENTRATION- RESPONSE RELATIONSHIPS WITHIN STRATA DEFINED BY DIFFERENT PM2.5 COMPOSITION AND OXIDATIVE POTENTIAL.