Fresno Asthmatic Children\'s Environment Study

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Fresno Asthmatic Children's Environment Study (FACES) and the U.S. the Fresno field staff ......

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Fresno Asthmatic Children’s Environment Study (FACES) Final Report

April 25, 2006 ARB Contract Nos. 99-322 by Ira Tager S. Katharine Hammond John Balmes Mervi Hjelmroos-Koski Jennifer Mann Kathleen Mortimer Romain Neugebauer Mark van der Laan University of California, Berkeley Berkeley, CA Fred Lurmann Paul Roberts Siana Alcorn David Vaughn Sonoma Technologies, Inc. Petaluma, CA Helene Margolis California Air Resources Board Sacramento, CA Janet Macher California Department of Health Services Richmond, CA Prepared for the Research Division California Air Resources Board Sacramento, CA i

AUTHORS The principle investigators on the Fresno Asthmatic Children’s Environment Study include: Drs. Ira Tager and Katharine Hammond of the University of California, Berkeley (UCB). Additional investigators include Dr. John Balmes of University of California, San Francisco (UCSF) and UCB, Fred Lurmann and Dr. Paul Roberts of Sonoma Technologies Incorporated (STI), Dr. Helene Margolis of the California Air Resources Board (CARB) and the California Department of Health Services (DHS), Dr. Janet Macher (DHS), Dr. Jennifer Mann (UCB), Dr. Kathleen Mortimer (UCB), Dr. Romain Neugebauer (UCB), Dr. Mark van der Laan (UCB). Additional authors of this report include Dr. Mervi Hjelmroos-Koski (UCB), Siana Alcorn (STI), and David Vaughn (STI). ACKNOWLEDGMENTS The authors wish to thank the California Air Resources Board (CARB) for sponsoring the Fresno Asthmatic Children’s Environment Study (FACES) and the U.S. Environmental Protection Agency Office of Transportation and Air Quality, especially Dr. Richard Baldauf, for sponsoring the Fresno polycyclic aromatic hydrocarbon (PAH) monitoring. The authors acknowledge the efforts of numerous members of the CARB project staff, especially Richard Bode, Ken Bowers, Steve Hui, Peggy Jenkins, Sally Jorgensen, Karen Magliano, Clint Taylor, Barbara Weller, Dane Westerdahl and Jeff Yanowsky for implementing the mobile trailers, arranging to have the continuous PAH monitors operated in the trailers, allowing access to the trailers and Supersite for integrated sampling, and for ongoing administrative support. The authors wish to thank Judith Chow, Dana Trimble, and John Watson of the Desert Research Institute (DRI) for sharing preliminary data from the Fresno Supersite. Additional thanks are due to Hal Farber for his help in our recruitment efforts through Kaiser Permanente and members of the FACES External Advisory Committee, which includes Drs. David Bates, Homer Boushey, Judith Chow, Paul Enright, Mort Lippmann, Michael Lipsett, Suresh Moolgavkar, Raymond Neutra, Mark Segal, Frank Spiezer, Lianne Sheppard and Lance Wallace (former member). We thank the Fresno field staff including Cynthia Appel, Kathy Butler, Alex Gabaldon, Raul Gallegos, Leah Melendez, Mia Ortega, and Pamela Powers. The contributions of the following STI staff are gratefully acknowledged: Juliet Doty, Kristi Hansen, Rodman Leach, Cindy Sauls, Tami Funk, Manidipa Ghosh, Nicole Hyslop, Mike McCarthy, Theresa O'Brien, Bryan Penfold, and Sean Raffuse. The contributions of the following Holland and Hammond laboratory staff at UCB are gratefully acknowledged: Maria Bastaki, Dan Burley, Margaret Cheng, Edwin Fung, Christina Ha, Megan Hiltz, Dr. Nina Holland, Diana Jeschke, Kasia Kaczmarek, Sa Liu, Betsey Noth, Charles Perrino and Masahiko Sugiura. In addition we gratefully acknowledge the contributions of CARB’s trailer operations contractors, Dave Wilkerson and Dave Wright, and CARB’s quality assurance contractor, Dave Bush. The cooperation received from UCB research and administrative staff, including Keith Betts, Lucas Carlton, Dr. Andre Fallot, Melanie Gendell, Tad Haight, Phil Lowenthal, Elizabeth MacDonald, Elizabeth Matovinovic, Jamie Mikkelsen, Jessie Murphy, Dr. Long Ngo, Bao Nguyen, Boriana Pratt, Huaxia Qin, Sandra Sinisi, Yue Wang, Patricia Segrestan, Ken Tang, and Dawn Wallace, is greatly appreciated. We are grateful for the technical support provided by Jerry Masiello of ndd Medical Devices, Inc.

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DISCLAIMER The statements and conclusions in this Report are those of the contractor and not necessarily those of the California Air Resources Board. The mention of commercial products, their source or their use with material reported herein is not to be construed as actual or implied endorsement of such products.

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1.

EXECUTIVE SUMMARY ................................................................................................. 1-2 1.1 Project Overview ......................................................................................................... 1-2 1.1.1 Background and Public Health Significance ........................................................... 1-2 1.1.2 Study Goal, Research Questions and Hypotheses ................................................... 1-3 1.2 Methods........................................................................................................................ 1-4 1.2.1 Study Design and Population................................................................................... 1-4 1.2.2 Health Assessment ................................................................................................... 1-5 1.2.3 Exposure Assessment............................................................................................... 1-6 1.2.4 Analytic Strategy ..................................................................................................... 1-7 1.3 Results.......................................................................................................................... 1-9 1.3.1 Study Population Characteristics ............................................................................. 1-9 1.3.2 Exposure Characterization ..................................................................................... 1-10 1.3.3 Health Effects Analyses......................................................................................... 1-12 1.3.3.1 Short-term Effects:............................................................................................. 1-14 1.3.3.2 Medium-Term Effects (Expected over Four Years of Observation): ................ 1-15 1.4 Conclusions and the Future of FACES...................................................................... 1-16

2.

INTRODUCTION ............................................................................................................... 2-1 2.1 Background .................................................................................................................. 2-1 2.1.1 Background Presented in Original FACES Application, September 2000.............. 2-1 2.1.2 Background Presented in Interim Report, July 2002 ............................................... 2-6 2.1.3 Updated Background from Interim Report to the Present ..................................... 2-10 2.2 Public Health Significance......................................................................................... 2-15 2.3 Biological Rationale................................................................................................... 2-16 2.4 Hypotheses (As presented in the original application) .............................................. 2-18 2.4.1 Short-term Effects.................................................................................................. 2-19 2.4.2 Medium-Term Effects (Expected over Four Years of observation) ...................... 2-20

3.

METHODS .......................................................................................................................... 3-1 3.1 Introduction.................................................................................................................. 3-1 3.2 Study design................................................................................................................. 3-1 3.2.1 Overview and Rationale........................................................................................... 3-1 3.2.2 Health Assessment Protocols................................................................................... 3-2 3.2.2.1 Assessment of Lung Function.............................................................................. 3-2 3.2.2.1.1 EasyOne® Spirometry for Panel Visits ............................................................ 3-2 3.2.2.1.2 Spirometry During Field Office Visits ............................................................ 3-3 3.2.2.1.3 Quality Control/Quality Assurance for Lung Function Measures................... 3-4 3.2.2.1.4 Bronchodilator Protocol................................................................................... 3-5 3.2.2.2 Allergen Skin Test Panel ..................................................................................... 3-6 3.2.2.3 Nutritional Assessment ........................................................................................ 3-6 3.2.2.4 Collection of Samples for DNA Testing.............................................................. 3-7 3.2.2.4.1 Blood Samples ................................................................................................. 3-7 3.2.2.4.2 Buccal Cell Collection ..................................................................................... 3-7 3.2.3 Questionnaires and Visits ........................................................................................ 3-8 3.2.3.1 Overview.............................................................................................................. 3-8 3.2.3.2 Screening.............................................................................................................. 3-8 iii

3.2.3.3 Baseline................................................................................................................ 3-8 3.2.3.4 Telephone Questionnaire ..................................................................................... 3-9 3.2.3.5 Field Office Visits................................................................................................ 3-9 3.2.3.6 Panel Visits .......................................................................................................... 3-9 3.2.3.6.1 Home Survey ................................................................................................. 3-10 3.2.3.6.2 Two-Week Diary ........................................................................................... 3-11 3.2.3.7 Development of Questionnaires......................................................................... 3-12 3.2.4 Quality Assurance/Quality Control for Questionnaires......................................... 3-17 3.3 Study populations....................................................................................................... 3-19 3.3.1 Eligibility ............................................................................................................... 3-19 3.3.2 Development of the Cohort of Children with Asthma........................................... 3-20 3.3.2.1 Recruitment........................................................................................................ 3-20 3.3.2.1.1 Recruitment Strategies ................................................................................... 3-20 3.3.2.1.2 Screening and Exclusions .............................................................................. 3-24 3.3.3 Characteristics of All Potential Participants Screened........................................... 3-25 3.3.4 Participation Levels ............................................................................................... 3-26 3.3.4.1 Field Office Visits.............................................................................................. 3-27 3.3.4.2 Telephone Interviews......................................................................................... 3-27 3.3.4.3 Field Office Spirometry ..................................................................................... 3-28 3.3.4.4 Completion of other Field Office Clinical Procedures ...................................... 3-28 3.3.4.4.1 Buccal Cell Samples ...................................................................................... 3-28 3.3.4.5 Nutrition Survey................................................................................................. 3-29 3.3.4.6 Allergy Skin Testing .......................................................................................... 3-29 3.3.4.7 Participation for Follow-up Visits ..................................................................... 3-29 3.3.4.8 Panel Visits ........................................................................................................ 3-29 3.3.4.8.1 Daily Diary Data:........................................................................................... 3-30 3.3.4.8.2 EasyOne® Data ............................................................................................. 3-30 3.4 Exposure Assessment methodology .......................................................................... 3-38 3.4.1 Exposure Assessment Study Design...................................................................... 3-38 3.4.2 Measurement Methods at the Central Site, Schools, and other Fixed Sites .......... 3-46 3.4.2.1 Aerometric Measurements Conducted by ARB and DRI.................................. 3-46 3.4.2.2 Endotoxin Measurement Methods ..................................................................... 3-46 3.4.2.3 Pollen Grain and Fungal Spore Measurement Methods .................................... 3-47 3.4.2.3.1 Sampling of Pollen Grains and Fungal Spores at Central Site and Trailers .. 3-47 3.4.2.3.2 Analysis of collected samples for pollen grains and fungal spores (same for both Central Site and home intensive samples) ................................................................... 3-48 3.4.2.3.3 Pollen Grains and Fungal Spore Identification.............................................. 3-48 3.4.2.3.4 Calculation of the pollen grain and fungal spore concentrations collected with Burkard sampler................................................................................................................... 3-49 3.4.2.3.5 Time Resolution............................................................................................. 3-50 3.4.2.3.6 Data Quality Control...................................................................................... 3-50 3.4.2.4 Polycyclic Aromatic Hydrocarbons................................................................... 3-51 3.4.2.4.1 Naphthalene ................................................................................................... 3-51 3.4.2.4.2 Coating Filters and Denuders......................................................................... 3-52 3.4.2.4.3 Sample Collection.......................................................................................... 3-52 3.4.2.4.4 Sample Storage and Shipment ....................................................................... 3-52 iv

3.4.2.4.5 Sample Extraction.......................................................................................... 3-53 3.4.2.4.6 Analysis.......................................................................................................... 3-53 3.4.2.5 Quality Assurance and Quality Control............................................................. 3-53 3.4.3 Routine Home Exposure Measurement Methods .................................................. 3-65 3.4.3.1 Moisture Protocol............................................................................................... 3-66 3.4.3.2 NO2 Measurement Methods............................................................................... 3-66 3.4.3.3 Ozone Measurement Methods ........................................................................... 3-66 3.4.3.4 Nicotine Measurement Methods ........................................................................ 3-67 3.4.3.5 Household Dust Collection Weighing, and Storing........................................... 3-67 3.4.3.6 Dust Allergens Measurement Methods.............................................................. 3-68 3.4.3.7 Dust Endotoxin Measurement Methods............................................................. 3-68 3.4.4 Home Intensive Study Measurement Methods ...................................................... 3-68 3.4.4.1 Sampling Strategy and Home Selection ............................................................ 3-69 3.4.4.2 Microenvironmental Exposure Monitoring System (MEMS) ........................... 3-69 3.4.4.2.1 PM Mass, Inorganic Ions, Carbon, and Trace Metals.................................... 3-70 3.4.4.2.2 Polycyclic Aromatic Hydrocarbons............................................................... 3-71 3.4.4.2.3 Light Scattering by Particles Measured With a Nephelometer...................... 3-71 3.4.4.2.4 Endotoxins ..................................................................................................... 3-72 3.4.4.2.5 Pollen Grains and Fungal Spores................................................................... 3-72 3.4.4.2.6 Ozone and NO2 .............................................................................................. 3-73 3.4.4.2.7 Nicotine Measurement Methods (See Appendix F)....................................... 3-73 3.4.4.2.8 Home Intensive Study House Activity Survey .............................................. 3-73 3.4.5 Quality Assurance and Quality Control Summary ................................................ 3-76 3.4.5.1 Data Validation and Adjustments for the Fixed-Site Continuous Data............. 3-76 3.4.5.1.1 Background .................................................................................................... 3-76 3.4.5.1.2 Data Validation Procedures ........................................................................... 3-77 3.4.5.1.3 Central Site PPAH Monitor Calibration ........................................................ 3-77 3.4.5.1.4 Comparison of the Central Site and Trailer Data........................................... 3-78 3.4.5.1.5 Continuous Database ..................................................................................... 3-80 3.4.5.1.6 Data Adjustments Applied to FACES Continuous Carbon, Nitrate, and Sulfate Data 3-81 3.4.5.2 Sampling and Laboratory Procedures to Provide Quality Control Data............ 3-82 3.4.5.3 Summary of Precision Estimates for the FACES Exposure Data...................... 3-82 3.4.6 Residence Geocoding and Traffic Assignments .................................................. 3-105 3.4.6.1 Residence Geocoding....................................................................................... 3-105 3.4.6.2 Traffic Assignments......................................................................................... 3-106 3.4.7 Exposure Modeling.............................................................................................. 3-110 3.4.7.1 Background ...................................................................................................... 3-110 3.4.7.2 FACES Individual exposure Model................................................................. 3-111 3.4.7.2.1 Time-activity................................................................................................ 3-111 3.4.7.2.2 Outdoor Concentrations ............................................................................... 3-112 3.4.7.2.3 Indoor Concentrations.................................................................................. 3-114 3.4.7.2.4 Non-Residential Locations........................................................................... 3-116 3.4.8 Exposure Metrics ................................................................................................. 3-125 3.5 Health Outcomes/Endpoints Methodology.............................................................. 3-132 3.5.1 Development of Health Outcomes and other Endpoints of Interest .................... 3-132 v

3.5.1.1 Spirometry........................................................................................................ 3-132 3.5.1.1.1 Spirometry for Field Office Visits ............................................................... 3-132 3.5.1.1.2 Spirometry for 14-Day Panel Studies .......................................................... 3-133 3.5.1.2 Asthma Symptoms ........................................................................................... 3-134 3.5.1.3 Classification of Asthma Severity ................................................................... 3-134 3.5.1.4 Skin-prick Tests and Designation of Atopic Status ......................................... 3-135 3.5.2 Health Outcomes Included in the Analyses in the Final Report.......................... 3-136 3.5.2.1 Acute Effects.................................................................................................... 3-136 3.5.2.2 Chronic Effects ................................................................................................ 3-137 3.6 Statistical Analytic Methods .................................................................................... 3-137 3.6.1 Overview of Health Analyses in Final Report..................................................... 3-137 3.6.2 Motivation for Use of Marginal Structural Models (MSM) ................................ 3-137 3.6.3 Summary of Three MSM Estimators................................................................... 3-141 3.6.4 Non-Parametric MSM Causal Effects and History-Restricted MSM.................. 3-141 3.6.5 Data-Adaptive Estimation/Model Selection and Application of the Deletion/Substitution/Addition (DSA) Algorithm............................................................. 3-142 3.6.6 Strategies for Handling Missing Data.................................................................. 3-142 3.6.7 Repeated Measures .............................................................................................. 3-143 3.6.8 Methods for the Conventional Analysis of Short-term Effects ........................... 3-143 3.6.9 Chronic Analysis of Acute Pollutant Effects ....................................................... 3-144 3.6.10 Methods used for Analysis of Altered Pulmonary Function and Highway Traffic Near the Residence (See Appendix J for additional details).............................................. 3-145 3.6.10.1 Pulmonary Function......................................................................................... 3-145 3.6.10.2 Potential Effect Modifiers (Severity and Atopy) ............................................. 3-145 3.6.10.3 Traffic .............................................................................................................. 3-145 3.6.10.4 Ambient Air Quality and Meteorological Data: .............................................. 3-146 3.6.10.5 Questionnaire-Based Exposure Information.................................................... 3-146 3.6.10.6 Statistical Analyses .......................................................................................... 3-146 4.

RESULTS ............................................................................................................................ 4-1 4.1 Exposure Assessment................................................................................................... 4-1 4.1.1 Air Quality Conditions at the Central Site, Schools, and other Fixed Sites ............ 4-1 4.1.1.1 Summary Statistics............................................................................................... 4-1 4.1.1.2 Seasonal Characteristics....................................................................................... 4-1 4.1.1.3 Day-to-day Characteristics................................................................................... 4-5 4.1.1.4 Diurnal Characteristics......................................................................................... 4-8 4.1.1.5 Relationships among Continuously Measured Parameters................................ 4-10 4.1.2 Housing Characteristics and Exposures Reported at Baseline .............................. 4-85 4.1.2.1 Housing Characteristics ..................................................................................... 4-85 4.1.2.1.1 Heating........................................................................................................... 4-85 4.1.2.1.2 Cooling........................................................................................................... 4-85 4.1.2.1.3 Gas Appliances .............................................................................................. 4-85 4.1.2.1.4 Air Cleaners and Dehumidifiers .................................................................... 4-86 4.1.2.1.5 Pets................................................................................................................. 4-86 4.1.2.1.6 Other sources of indoor air pollution and allergen exposure......................... 4-86 4.1.2.1.7 Second Hand Smoke Exposures .................................................................... 4-86 4.1.2.1.8 Potential sources of outdoor air pollution near the home .............................. 4-86 vi

4.1.2.2 Exposures Reported on the Daily Diary ............................................................ 4-87 4.1.2.2.1 Heating, Cooling and Ventilation .................................................................. 4-87 4.1.2.2.2 Other Daily Indoor Exposures ....................................................................... 4-87 4.1.3 Time-Location-Activity during Panel Visits ......................................................... 4-92 4.1.4 Indoor Air Quality Conditions in Homes............................................................... 4-93 4.1.4.1 Home Intensive Measurements.......................................................................... 4-93 4.1.4.2 Routine House Measurements ........................................................................... 4-95 4.1.4.2.1 Dust Samples ................................................................................................. 4-95 4.1.4.2.2 Endotoxin....................................................................................................... 4-96 4.1.4.2.3 Passive Samples: Nicotine, NO2 and Ozone................................................. 4-96 4.1.4.2.4 Moisture Levels in Participants Homes as Measured at the Home Visit....... 4-97 4.1.4.3 First Visit Report of Routine Residential Measurements .................................. 4-98 4.1.5 Indoor - Outdoor Pollutant Relationships at Residences ..................................... 4-118 4.1.6 Spatial Variability in Ambient Air Quality.......................................................... 4-134 4.1.6.1 Visual observations of Spatial Patterns............................................................ 4-134 4.1.6.2 Spatial Variability ............................................................................................ 4-135 4.1.6.3 Systematic Spatial Variation and Spatial Representativeness ......................... 4-137 4.1.6.4 Pollutant Relationships to Traffic .................................................................... 4-140 4.1.7 Exposure Modeling.............................................................................................. 4-168 4.1.8 Exposure Summary.............................................................................................. 4-177 4.1.8.1 Specific Aims................................................................................................... 4-177 4.1.8.2 Findings............................................................................................................ 4-178 4.2 Pollution-related health outcomes............................................................................ 4-180 4.2.1 Descriptive Analyses of Cohort ........................................................................... 4-180 4.2.1.1 Health Characteristics at Baseline ................................................................... 4-180 4.2.1.2 Asthma Symptoms at Baseline ........................................................................ 4-181 4.2.1.3 Triggers ............................................................................................................ 4-182 4.2.1.4 Panel Visits ...................................................................................................... 4-182 4.2.1.4.1 Symptoms and Medication use Reported in the Daily Diary ...................... 4-182 4.2.1.4.2 Symptoms and Medication Use Data from the EasyOne® ......................... 4-182 4.2.1.4.3 Pulmonary Function During Study Panels................................................... 4-183 4.2.2 Results of Short-term Effects Analyses ............................................................... 4-196 4.2.2.1 Introduction and Conventional Analyses......................................................... 4-196 4.2.2.2 Influence of Medication Use on the Effect of Pollutants on Pulmonary Function 4200 4.2.2.3 Summary of Conventional Acute Analyses..................................................... 4-201 4.2.2.4 Preliminary Analyses of Symptom and Rescue Medication Outcomes (Presented previously as part of Interim Report - August 26, 2002)................................................... 4-201 4.2.3 Marginal Structure Model Analysis: (See section 3.6 for a summary and Appendix I for theoretical details of the statistical methods). .............................................................. 4-214 4.2.3.1 General Comments about the Presentation of the MSM Data......................... 4-217 4.2.3.2 Effect of Estimated Individual exposure to PM2.5 and Rescue Medication Use on A.M. FEV1 ......................................................................................................................... 4-219 4.2.3.3 Effect of Exposure to Central Site Concentrations of PM2.5 and Rescue Medication Use on A.M. FEV1 .......................................................................................... 4-219

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4.2.3.4 Effect of Estimated Individual exposure to PM2.5 and Rescue Medication Use on A.M. FEF25-75. .................................................................................................................... 4-220 4.2.3.5 Effect of Exposure to Central Site Concentrations of NO and Rescue Medication Use on A.M. FEV1 ............................................................................................................. 4-220 4.2.3.6 Effect of Exposure to Estimated Individual exposure and Central Site Concentrations of NO2 and Rescue Medication Use on A.M. FEV1 ................................. 4-221 4.2.4 Methods and Analysis of Chronic Effect of Acute Responses on Pulmonary Function Growth ................................................................................................................ 4-242 4.2.5 Altered Pulmonary Function Associated with Highway Traffic Near Residence4-245 5.

INTEGRATED SUMMARY AND CONCLUSIONS........................................................ 5-1 5.1 General Summary Related to Cohort........................................................................... 5-1 5.2 General Summary of Conclusions from Exposure Component................................... 5-1 5.3 Summary for Analyses of Pollutant EfFECTS on Lung Function: ............................. 5-4 5.3.1 General Comments................................................................................................... 5-4 5.3.1.1 Associations with Daily changes in Air Pollutants.............................................. 5-4 5.3.2 Comments on the Analyses Presented ..................................................................... 5-8 5.3.3 Summary Accomplishments Relative to Specific Aims........................................ 5-11 5.3.3.1 Specific Aims for Exposure Component ........................................................... 5-11 5.3.3.2 Specific Aims for the Health Component.......................................................... 5-12 5.3.3.3 Medium-Term Effects (Expected over Four Years of observation) .................. 5-13

6.

REFERENCES .................................................................................................................... 6-1

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List of Tables 3.2.2-1 3.2.3-1 3.2.3-2 3.2.3-3 3.2.3-4 3.2.3-5a 3.2.3-5b 3.2.3-6 3.2.3-7 3.2.3-8 3.2.3-9 3.3.1-1 3.3.1-2 3.3.2-1 3.3.2-2 3.3.2-3 3.3.3-3 3.3.4-1 3.3.4-2 3.3.4-3 3.3.4-4 3.3.4-5 3.3.4-6 3.3.4-7 3.3.4-8 3.3.4-9 3.3.4-10 3.3.4-11 3.3.4-12 3.3.4-13 3.3.4-14 3.3.4-15 3.3.4-16 3.3.4-17 3.3.4-18 3.3.4-19 3.4.1-1 3.4.1-2 3.4.1-3 3.4.2-1 3.4.2-2 3.4.2-3

3.4.2-4 3.4.2-5

Well Skin Test Solutions Content of Screening Questionnaire Content of Adult Baseline Visits Content of Child Baseline Visits Content of Telephone Survey (asked to adults only) Adult Field Office Visit Questionnaire Child Field Office Visits Questionnaire Special One-time Components of Adult Field Office Visit Questionnaires Content of Panel Visit Original Time-activity codes for panel diaries Data Collection Dates Eligibility Criteria for FACES Summary of Eligibility Criteria Evaluations of Recruitment Methods Reasons for Ineligibility at Screening Enrollment over time Description of Participants (Percentage) Activity Levels (N=315) Distribution of Years in the Study after Baseline Field Office Visit Participation Levels Telephone interview Participation Levels Total Number of Follow-up Contacts Completed for Each Child by June 30, 2005 Distribution of Number of Contacts by June 30, 2005 Total Number of Follow-up Contacts Completed for Each Child by March 31, 2003 Distribution of Number of Contacts by March 31, 2003 Field Office Spirometry Data as of September 30, 2003 Number of Buccal Cell Samples for Children, Mothers and Fathers Buccal Cell Completion for Each Family Number of Nutrition Surveys Completed Total Number of Panel Visits Completed by Each Participant Percentage Participation for Panel Visits Number of Seasons of Environmental Samples Number of Homes with Environmental Samples for Each Season Data Completion for the Daily Diary Summary of Panel Visit Spirometry Data Quality Number of Sessions Expected for Analysis as of June 30, 2005 Target Agents for Exposure Assessment in FACES Agents Sampled and Sample Duration at Various Locations Exposure Assessment for FACES Aerometric measurements conducted by ARB and DRI at the Central Site for FACES Elements determined in x-ray fluorescence analysis of Teflon filters collected at the Central Site Pollen grains and fern spores in air samples from Fresno, California, with identification of the proposed 14 pollen-grain groups (P1–P14) that were analyzed separately from total pollen grain concentration (P15 = sum of all 124 taxa). Known allergenic pollen-grain groups shown in bold. Fungal spores and algal cells observed in air samples from Fresno, California, with identification of the proposed four spore groups (F1–F4) that were identified if considered separately from total indicator spore concentration (F5). Medians of 24-hour Average Concentrations of Proposed Indicator Pollen and Fungal Groups in Fresno, CA

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3-27 3-32 3-33 3-33 3-34 3-34 3-35 3-35 3-35 3-36 3-36 3-40 3-40 3-45 3-45 3-45 3-46 3-52 3-52 3-52 3-53 3-53 3-53 3-54 3-54 3-54 3-55 3-55 3-55 3-56 3-56 3-56 3-56 3-57 3-57 3-57 3-62 3-63 3-64 3-74 3-75 3-76

3-80 3-83

3.4.2-6 3.4.4-1 3.4.5-1 3.4.5-2 3.4.5-3 3.4.5-4 3.4.5-5 3.4.5-6 3.4.5-7 3.4.7-1 3.4.7-2 3.4.7-3 3.4.7-4 3.4.7-5 3.4.7-6 3.4.7-7 3.4.8-1 3.4.8-2 3.4.8-3 3.5.1-1 4.1.1-1 4.1.1-2 4.1.1-3 4.1.1-4 4.1.1-5 4.1.1-6 4.1.1-7 4.1.1-8 4.1.1-9 4.1.1-10 4.1.1-11 4.1.2-1 4.1.2-2 4.1.2-3 4.1.2-4

The mass ions chosen and the retention time for each PAH analyzed during FACES Filter arrangement and specifications for the five impactors in the MEMS Time Periods and Pollutants Available by Site Results from STI’s Re-Evaluation of ARB’s Comparison Between Central Site and Trailer Instruments Parameter adjustment equations used to improve comparability with First Street measurements. FACES MAY 2002 INTER-COMPARISON RESULTS AFTER ADJUSTMENTS WERE MADE Calculation method by exposure metric category. All metrics are calculated from the 24-hr period spanning 8 p.m. on the sample start date to 8 p.m. on the sample end date. Percent data completeness by site and pollutant. The total number of expected days is also listed. Collocated Comparison Statistics for FACES PM, Carbon, and Endotoxin Samples Average Time-Use for Children by Day Type and Time Period. Alternate Time-Use for Various Diary Activity Responses Summary Statistics of Ratios of Estimated Concentrations at FACES Residences to Central Site Concentrations Penetration factors and indoor loss rates for selected pollutants Daily Housing and Activity Related Parameters PM2.5 Sulfate I/O Ratios in FACES Residences in Different Seasons with Different Windows/Doors Positions and HVAC Operating Modes In-transit Pollutant Concentrations FACES Daily Exposure Metric Averaging Times by Group Parameters Contained in the FACES Exposure Metrics Database Exposure Modeling Database Contents Range of Area Under the Receiver-Operator Curves (C-Statistic) for Various Asthma Severity Classification Algorithms Summary statistics for pollutant concentrations at Fresno Central site based on 24-hr averages for 4/1/2001 to 3/31/2003. Summary statistics for pollutant concentrations at Fremont site based on 24-hr averages for 6/10/2002 to 3/31/2003. Summary statistics for pollutant concentrations at Bullard site based on 24-hr averages for 6/10/2002 to 7/25/2002. Summary statistics for pollutant concentrations at Viking based on 24-hr averages for 7/26/2002 to 9/27/2002. Summary statistics for pollutant concentrations at Burroughs site based on 24-hr averages for 10/1/2002 to 11/19/2002. Summary statistics for pollutant concentrations at Copper Hills site based on 24-hr averages for 11/24/2002 to 1/8/2003. Summary statistics for pollutant concentrations at Forkner site based on 24-hr averages for 1/9/2003 to 2/19/2003. Summary statistics for pollutant concentrations at Holland site based on 24-hr averages for 2/20/2003 to 3/31/2003. Summary statistics for pollutant concentrations at Clovis site based on 24-hr averages for 4/1/2001 to 3/31/2003 Summary statistics for pollutant concentrations at Drummond site based on 24-hr averages for 4/1/2001 to 3/31/2003 Summary statistics for pollutant concentrations at Sierra Sky Park site based on 24-hr averages for 4/1/2001 to 3/31/2003 Home Heating in Child’s Home to March 31, 2003 Sources of Cooling reported at baseline Gas appliances in child’s home to March 31, 2003 Air cleaners/Dehumidifier use at baseline, to March 31, 2003

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3-85 3-94 3-104 3-105 3-106 3-107 3-107 3-107 3-109 3-137 3-138 3-139 3-139 3-140 3-140 3-141 3-145 3-146 3-150 3-155 4-12 4-16 4-23 4-24 4-30 4-32 4-36 4-40 4-43 4-43 4-44 4-88 4-89 4-89 4-89

4.1.2-5 4.1.2-6 4.1.2-7 4.1.2-8 4.1.2-9 4.1.2-10 4.1.3-1 4.1.4-1 4.1.4-2 4.1.4-3 4.1.4-3 4.1.4-5 4.1.4-6 4.1.4-7 4.1.4-8 4.1.5-1 4.1.5-2 4.1.5-3 4.1.6-1 4.1.6-2 4.1.6-3 4.1.6-4 4.1.7-1 4.2.1-1a 4.2.1-1b 4.2.1-2 4.2.1-3 4.2.1-4 4.2.1-5 4.2.1-6 4.2.1-7 4.2.1-8 4.2.1-9 4.2.1-10 4.2.1-11 4.2.1-12 4.2.1-13 4.2.1-14 4.2.1-15 4.2.1-16 4.2.2-1

Pets reported in child’s home at baseline (N=235) Other potential sources of indoor air problems Self-reported Exposures in the Home at Baseline (N=315) Smoking Policy or Rules in the Home (N=167) Potential sources of outdoor air pollution near the home 4.1.2.-10 Daily Exposures in the Home as Reported in the Daily Diary (November 30, 2000 to March 31, 2003) Responses to Time/Location/Activity Questions on Daily Diary Summary statistics for indoor pollutant concentrations in FACES residences based on all 24hr samples that exceeded the limits of detection Summary statistics for the average indoor pollutant concentrations in FACES residences Dust Concentrations: Samples Collected in the Home to March 31, 2003 Endotoxin in House Dust (EU/mg) Distribution of Concentrations for 2-week passive samples taken in the home (November 30, 2000 to March 31, 2003) Periods that Ozone passive samplers were deployed (2000 to 2004) Comparison of distributions by Study Season (November 30, 2000 to March 31, 2003) Distribution of Pulmonary Function Measures (November 28, 2000 to March 31, 2003) Summary statistics for outdoor pollutant concentrations at FACES residences based on all 24-hr samples that exceeded the limits of detection Summary statistics for the indoor/outdoor ratios in FACES residences based on concurrent 24-hr concentrations that were not outliers2 and exceeded the limits of detection Correlation of indoor and outdoor concentrations at FACES residences Mean daily spatial coefficients of variation in 24-hr average concentrations in Fresno Relative ranking of outdoor pollutant concentration spatial variability in Fresno Descriptive statistics of ratios of 24-hr average concentrations at schools, residences, and other air quality stations in the community to those at the central site in Fresno Coefficient of determination (r2) for associations between traffic density and freeway traffic metrics, and the ratio of PM chemical component to central site levels across Fresno Comparison of mean estimated individual exposure and mean central site ambient concentrations on panel study days Age Distribution at each follow-up visit (November 28, 2000 to July, 2005) Age Distribution at each follow-up visit (November 28, 2000 to March 31, 2003) Demographic characteristics in the Fresno population and in the FACES Cohort at Baseline Health Characteristics at Baseline Pulmonary Function at Baseline Asthma Symptoms Reported at Baseline Skin Test Positivity: Percent positive to each allergen (N=266) Comparison of self-reported diagnosis of allergic rhinitis and skin-test results Wheezing triggers during lifetime and in the past 12 months Frequency of “YES” Responses to Diary Questions Percent of “YES” Responses to EasyOne® Questions (November 28, 2000 to March 31, 2000 Percent of “YES” Responses to EasyOne® Questions by Season (November 28, 2000 to March 31, 2003 Distribution of Daily Counts (YES Responses to A.M. EasyOne® Questions) November 28, 2000 to March 31, 2003) (N=718 days) Distribution of Pulmonary Function Measures (November 28, 2000 to March 31, 2003) Comparison of Morgan and EasyOne data stratified by gender and age group. Distribution of Daily Pulmonary Function Values by Season (November 28, 2000 to March 31, 2003) Distribution of Daily Pulmonary Function Measures by Study Period (November 28, 2000 to March 31, 2003) Results of Conventional Analysis of Association Between Daily Levels in Estimated

xi

4-89 4-90 4-90 4-90 4-90 4-91 4-93 4-99 4-102 4-105 4-105 4-106 4-106 4-106 4-107 4-121 4-128 4-133 4-154 4-160 4-162 4-166 4-179 4-188 4-188 4-189 4-190 4-191 4-191 4-192 4-192 4-193 4-193 4-194 4-194 4-195 4-196 4-197 4-198 4-199 4-206

4.2.2-2 4.2.2-3 4.2.2-4 4.2.2-5 4.2.2-6 4.2.2-7 4.2.2-8 4.2.2-9 4.2.2-10 4.2.3-1 4.2.3-2 4.2.3-3 4.2.3-4 4.2.3-5 4.2.3-6 4.2.3-7 4.2.3-8 4.2.3-9 4.2.3-10 4.2.3-11 4.2.3-12 4.2.3-13 4.2.3-14 4.2.3-15 4.2.3-16 4.2.3-17 4.2.4-1 4.2.5-1 4.2.5-2

Personal PM2.5 (µg/m3) and A.M. FEV1 (Liters) Results of Conventional Analysis of Association Between Daily Levels in Central Site PM2.5 (µg/m3) Concentrations and A.M. FEV1 (liters) Results of Conventional Analysis of Association Between Daily Levels in Estimated Personal Exposure to PM2.5 (µg/m3) and A.M. FEF25-75 (liters/second) Results of Conventional Analysis of Association Between Daily Levels in Estimated Personal PM2.5 (µg/m3) Exposure and A.M. FEF75 (liters/second) Results of Conventional Analysis of Association Between Daily Levels in Central Site NO (ppb) Concentrations and A.M. FEV1 (liters) Results of Conventional Analysis of Association Between Daily Levels in Estimated Personal Exposure to NO2 (ppb) and A.M. FEV1 (liters) Results of Conventional Analysis of Association Between Daily Levels in Central Site NO2 (ppb) and FEV1 (liters) Traditional Models of the Influence of Medication Use on the Effect of 2-day average NO2 on A.M. FEV1 Procedures for Analysis for a Given Pollutant Crude and Adjusted Odds Ratios For the Prevalence of Symptoms since bedtime Longitudinal MSM Results for Effect of Estimated Personal Exposure to PM2.5 on A.M. FEV1 Point-Treatment MSM Results for the Effect of Personal Exposure to PM2.5 and Rescue Medication Use on A.M. FEV1 (PM2.5 and Rescue Medication Use Forced in to the Model) Longitudinal MSM Results for Effect of Estimated Personal Exposure to PM2.5 on Use of Rescue Medication in the Hour Before A.M. Lung Function Testing Point-Treatment MSM Results for Effect of Estimated Personal Exposure to PM2.5 on Use of Rescue Medication in the Hour Before Morning Lung Function Testing Longitudinal MSM Results for Effects of Exposure to Central Site Levels of PM2.5 and Rescue Medicine Use on A.M. FEV1 Point-Treatment MSM Results for Effect of Exposure to Central Site Levels of PM2.5 on A.M. FEV1 Longitudinal MSM Results for Effects of Estimated Personal Exposure to PM2.5 and Rescue Medicine Use on A.M. FEF25-75 Point-Treatment MSM Results for Estimated Personal Exposure to PM2.5 on A.M. FEF25-75 Longitudinal MSM for Effects of Exposure to 24 Hour Central Site Concentrations of NO and Rescue Medicine on A.M. FEV1 Point-treatment MSM Results for Exposure to 24 Hour Central Site Concentrations of NO on A.M. FEV1 Longitudinal MSM Results for Estimated Personal Exposure to NO2 and Rescue Medicine Use on A.M. FEV1—Estimates Over All Seasons Point Treatment MSM Results for Effect of Estimated Personal Exposure to NO2 on A.M. FEV1 Longitudinal MSM for the Effect of Personal Exposure to NO2 on Rescue Medication Use in the Hour Before A.M. Lung Function Testing Point Treatment MSM for the Effect of Personal Exposure to NO2 on Rescue Medication Use in the Hour Before A.M. Lung Function Testing Longitudinal MSM Results for Exposure to 24 Hour Central Site Concentrations of NO2 and Rescue Medicine Use on A.M. FEV1on A.M. FEV1—Estimates Over All Seasons Point Treatment MSM for Effect of Exposure to Central Site NO2 on A.M. FEV1 Point Treatment MSM for the Effect of Exposure to Central Site NO2 on Rescue Medication Use in the Hour Before A.M. Lung Function Testing Distribution of Selected Variables for Demonstration of Approach to “Chronic” Analysis Association between highway traffic exposure metrics and measures of pulmonary function Interaction Between FEF25-75/FVC Ratio and Measures of Exposure to MVE From Freeways

xii

4-207 4-208 4-209 4-210 4-211 4-211 4-212 4-213 4-213 4-228 4-229 4-230 4-231 4-232 4-233 4-234 4-235 4-236 4-237 4-238 2-239 2-240 2-241 2-242 2-243 2-244 2-246 2-251 2-251

List of Figures 3.3.4-1 3.4.1-1 3.4.4-1 3.4.5-1 3.4.5-2 3.4.5-3 3.4.5-4 3.4.5-5 3.4.5-6 3.4.5-7 3.4.5-8 3.4.5-9 3.4.5-10 3.4.5-11 3.4.5-12 3.4.5-13 3.4.5-14 3.4.5-15 3.4.5-16 3.4.5-17 3.4.5-18 3.4.5-19 3.4.5-20 3.4.5-21 3.4.5-22 3.4.5-23 3.4.5-24 3.4.5-24 3.4.5-26 3.4.6-1 3.4.6-2 3.4.6-3 3.4.6-4: 3.4.7-1 3.4.7-2 3.6.2_1 4.1.1-1 4.1.1-2 4.1.1-3

Participation by Visit Time scale for sampling of air pollutants and biological agents during one home’s two-week panel study. Microenvironmental Exposure Monitoring System (MEMS) FACES trailer TC data adjusted to the First Street 5400 data based on the May 2002 intercomparison. R&P 5400 TC data adjusted to equivalence with filter-based MEMS data by multiplying by a factor of 1.83 FRM EC data were regressed on 24-hr average continuous BC data. Regression of Trailer 1 nitrate data on First Street nitrate data, May 2002 intercomparison. Regression of Trailer 2 nitrate data on First Street nitrate data, May 2002 intercomparison. The slope of the regression of First Street MEMS total nitrate versus First Street continuous sulfate compared well with FRM sulfate data. Scatter plot of MEMS duplicate PM10 samples. Scatter plot of MEMS versus BAM duplicate PM10 samples. MEMS versus RP 2025 PM10 at First Street. RP 2025 versus BAM PM10. Scatter plot of MEMS duplicate PM2.5 samples. Scatter plot of MEMS versus duplicate BAM PM2.5 samples. Scatter plot of MEMS duplicate EC samples. Scatter plot of MEMS versus EC_Calc duplicate samples. Scatter plot of MEMS versus EC_Calc duplicate samples, with the January 1, 2002, and January 11, 2002, outliers removed. Scatter plot of MEMS duplicate EC samples. Scatter plot of MEMS duplicate endotoxin samples. All points shown were used in precision estimate. Scatter plot of MEMS versus RP 2025 duplicate endotoxin samples. Scatter plot of MEMS duplicate total nitrate (front filter plus back filter) samples Scatter plot of MEMS duplicate sulfate samples. Scatter plot of MEMS duplicate aluminum samples. Scatter plot of MEMS duplicate silicon samples. Scatter plot of MEMS duplicate iron samples Scatter plot of MEMS duplicate iron samples Scatter plot of MEMS duplicate potassium samples. The distribution of distances from FACES residences to nearest freeways, arterial roadways, and collector roadways. The distribution of inverse-distance squared weighted traffic at FACES residences. Spatial maps of traffic density in Fresno near the central site based on the 150-meter (left) and 300-meter decay parameterization. The distribution of estimated traffic density at FACES residences based on the 150-meter decay parameterization Average spatial concentration gradients in Fresno and Clovis for PM2.5 mass, light scattering, PM2.5 OC, PM2.5 EC, PM10 mass, and PM2.5-10 mass expressed as ratios of ambient concentration to central site concentrations Average spatial concentration gradients in Fresno and Clovis for agricultural fungi, alternaria, cladosporium, total fungal spores, endotoxin, and total pollens expressed as ratios of ambient concentration to central site concentrations Directed acyclic graph of simple data structure Illustration of a box whisker plot as defined by SYSTAT statistical software Monthly box whisker plots of 24-hr average PM2.5 mass at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM10 mass at the Central Site (Fresno First

xiii

3-58 3-65 3-95 3-111 3-112 3-113 3-113 3-114 3-114 3-115 3-116 3-116 3-117 3-117 3-118 3-118 3-119 3-119 3-120 3-120 3-121 3-121 3-122 3-122 3-123 3-123 3-124 3-124 3-125 3-128 3-128 3-129 3-129 3-142 3-143 3-156 4-45 4-45 4-45

4.1.1-4 4.1.1-5 4.1.1-6 4.1.1-7 4.1.1-8 4.1.1-9 4.1.110. 4.1.1-11 4.1.1-12 4.1.1-13 4.1.114. 4.1.115. 4.1.116. 4.1.117. 4.1.118. 4.1.119. 4.1.120. 4.1.121. 4.1.122. 4.1.123. 4.1.124. 4.1.125. 4.1.126. 4.1.1-27 4.1.1-28 4.1.1-29 4.1.1-30

Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM2.5-10 (PM coarse) mass at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM2.5 number at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average particle scattering (bsp) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM2.5 EC at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM2.5 OC at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM2.5 nitrate (NO3) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average PM2.5 sulfate (SO4) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average particulate polycyclic aromatic hydrocarbons (PMPAH) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 8-hr daily maximum ozone (O3) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average carbon monoxide (CO) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average nitric oxide (NO) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average nitrogen dioxide (NO2) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average relative humidity (RH) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 24-hr average temperature (Temp) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 2 p.m. wind speed at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Monthly box whisker plots of 2 p.m. wind direction at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Daily (24-hr average) time series plot of PM2.5 mass (BAM2.5) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003. Daily (24-hr average) time series plot of PM10 mass (BAM10) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of PM2.5-10 mass (coarse, BAM2.5-10) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of PM2.5 number at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of particle scattering (bsp) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of elemental carbon (EC) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of organic carbon (OC) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of PM2.5 nitrate (NO3) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of PM2.5 sulfate (SO4) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of particulate polycyclic aromatic hydrocarbons (PMPAH) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (8-hr daily maximum) time series plot of ozone (O3) at the Central Site (Fresno First

xiv

4-43 4-46 4-46 4-46 4-47 4-47 4-47 4-47 4-48 4-48 4-48 4-48 4-49 4-49 4-49 4-49 4-50 4-50 4-51 4-51 4-52 4-52 4-53 4-53 4-54 4-54 4-55

4.1.1-31 4.1.132. 4.1.133. 4.1.134. 4.1.135. 4.1.136. 4.1.137. 4.1.138. 4.1.139. 4.1.140. 4.1.141. 4.1.142. 4.1.143. 4.1.144. 4.1.1-45 4.1.1-46 4.1.1-47 4.1.1-48 4.1.1-49 4.1.1-50 4.1.1-51 4.1.1-52 4.1.1-53 4.1.1-54 4.1.1-55 4.1.1-56 4.1.1-57

Street) for November 1, 2000, through April 30, 2002 Daily (24-hr average) time series plot of carbon monoxide (CO) at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002 Daily (24-hr average) time series plot of nitric oxide (NO) at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002. Daily (24-hr average) time series plot of nitrogen dioxide (NO2) at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002 Daily (24-hr average) time series plot of relative humidity at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002 Daily (24-hr average) time series plot of temperature at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002 Daily time series plot of 2 p.m. wind speed at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002 Daily time series plot of 2 p.m. wind direction at the Central Site (Fresno First Street) for November 1, 2000, through April 30, 2002 Daily (24-hr average) time series plot of Alternaria (ALTE) at the Central Site (Fresno First Street) for November 15, 2000, through March 31, 2003 Daily (24-hr average) time series plot of agricultural fungi (AGFG) at the Central Site (Fresno First Street) for November 1, 2000, through March 31, 2003 Daily (24-hr average) time series plot of Cladosporium (CLAD) at the Central Site (Fresno First Street) for November 15, 2000, through March 31, 2003 Daily (24-hr average) time series plot of Aspergillus/Penicillium (ASP) at the Central Site (Fresno First Street) for November 15, 2000, through March 31, 2003 Daily (24-hr average) time series plot of total fungal spores (TOTFS) at the Central Site (Fresno First Street) for November 15, 2000, through March 31, 2003 Daily (24-hr average) time series plot of endotoxin at the Central Site (Fresno First Street) for November 15, 2000, through March 31, 2003 Daily (24-hr average) time series plot of total pollen grains (TOP) at the Central Site (Fresno First Street) for November 15, 2000, through March 31, 2003 Daily (24-hr average) time series plot of PAH species acenaphthene (ACE) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species acenaphthylene (ACY) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species anthracene (ANT) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species benz[a]anthracene (BAA) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species benzo[a]pyrene (BAP) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species benzo[b]flouranthene (BBF) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species benzo[ghi]perylene (BGP) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species benzo[k]flouranthene (BKF) at the Central Site (Fresno First Street) for June 2002 through February 20 Daily (24-hr average) time series plot of PAH species chrysene (CRY) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species dibenz[a,h]anthracene (DBA) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species flouranthene (FLT) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species flourene (FLU) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species indeno[1,2,3-cd]pyrene (ICP) at the Central Site (Fresno First Street) for June 2002 through February 2003

xv

4-55 4-56 4-56 4-57 4-57 4-58 4-58 4-59 4-59 4-60 4-60 4-61 4-61 4-62 4-62 4-63 4-63 4-64 4-64 4-65 4-65 4-66 4-66 4-67 4-67 4-68 4-68

4.1.1-58 4.1.1-59 4.1.1-60 4.1.1-61 4.1.1-62 4.1.1-63 4.1.1-64 4.1.1-65 4.1.1-66 4.1.1-67 4.1.1-68 4.1.1-69 4.1.1-70 4.1.1-71 4.1.1-72 4.1.1-73 4.1.1-74 4.1.1-75 4.1.1-76 4.1.1-77 4.1.1-78 4.1.1-79 4.1.1-80 4.1.1-81 4.1.1-82 4.1.1-83 4.1.1-84 4.1.1-85

Daily (24-hr average) time series plot of PAH species napthalene (NAPST) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species phenathrene (PHE) at the Central Site (Fresno First Street) for June 2002 through February 2003 Daily (24-hr average) time series plot of PAH species pyrene (PYR) at the Central Site (Fresno First Street) for June 2002 through February 2003. Daily (24-hr average) time series plot of PM10 aluminum (AL) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 cobalt (CO) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 copper (CU) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 iron (FE) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 potassium (KP) at the Central Site (Fresno First Street) for May 2001 through April 2003; Daily (24-hr average) time series plot of PM10 manganese (MN) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 nickle (NI) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 silicon (SI) at the Central Site (Fresno First Street) for May 2001 through April 2003 Daily (24-hr average) time series plot of PM10 vanadium (VA) at the Central Site (Fresno First Street) for May 2001 through April 2003; Average diurnal profile of PM2.5 mass (BAM PM2.5) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of PM10 mass (BAM PM10) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of PM2.5-10 mass (coarse, BAM PM2.5-10 ) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of PM2.5 number at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of particle scattering (bsp) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of PM2.5 elemental carbon (EC) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 20 Average diurnal profile of PM2.5 organic carbon (OC) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 200 Average diurnal profile of PM2.5 nitrate (NO3) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2 Average diurnal profile of PM2.5 sulfate (SO4) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of particulate polycyclic aromatic hydrocarbons (PMPAH) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 200. Average diurnal profile of ozone (O3) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of carbon monoxide (CO) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003; concentrations are in ppm. Average diurnal profile of nitric oxide (NO) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of nitrogen dioxide (NO2) at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of relative humidity at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003. Average diurnal profile of temperature at the Central Site (Fresno First Street) for April 1,

xvi

4-69 4-69 4-70 4-70 4-71 4-71 4-72 4-72 4-73 4-73 4-74 4-74 4-75 4-75 4-75 4-76 4-76 4-76 4-77 4-77 4-77 4-78 4-78 4-78 4-79 4-79 4-79 4-80

4.1.1-86 4.1.1-87

4.1.1-88

4.1.1-89

4.1.1-90

4.1.1-91 4.1.4-1 4.1.4-2 4.1.4-3 4.1.4-4 4.1.4-5 4.1.4-6 4.1.4-7 4.1.4-8. 4.1.4-9. 4.1.4-10 4.1.5-1 4.1.5-2 4.1.5-3 4.1.5-4 4.1.5-5 4.1.5-6

2001, through March 31, 2003 Average diurnal profile of wind speed at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Average diurnal profile of wind direction at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003 Scatter-plot matrix of 24-hr average concentrations at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003: PM2.5 mass (PM25_MASS), PM10 mass (PM10_MASS), PM2.5-10 mass (PM_COARSE), PM2.5 number (PM25_NUMBER), particle scattering (BSCAT), PM2.5 elemental carbon (PM25_EC), PM2.5 organic carbon (PM25_OC), PM2.5 nitrate (PM25_NO3), PM2.5 sulfate (PM25_SO4), PM2.5 polycyclic aromatic hydrocarbons (PM25_PAH), 8-hr maximum ozone (O3_8HR_MAX), carbon monoxide (CO_), nitric oxide (NO), and 8-hr maximum nitrogen dioxide (NO2_8HR_max). Scatter-plot matrix of 24-hr average concentrations at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003: biological agents ALTE, AGFG, CLAD, ASP, TOTFS, ENDOTOXIN, AND TOP; gases NO and NO2; and PM2.5 elemental carbon (PM25_EC), PM2.5 organic carbon (PM25_OC), PM2.5 mass (PM25_MASS), PM10 mass (PM10_MASS), and PM2.5 sulfate (PM25_SO4). Scatter-plot matrix of 24-hr average concentrations at the Central Site (Fresno First Street) for April 1, 2001, through April 30, 2002: PM2.5 polycyclic aromatic hydrocarbons (PM25_PAH) and PAH species ACE, ACY, ANT, BAA, BAP, BBF, BGP, BKF, CRY, DBA, FLT, FLU, ICP, NAPST, PHE, and PHY. Scatter-plot matrix of 24-hr average concentrations at the Central Site (Fresno First Street) for April 1, 2001, through March 31, 2003: PM2.5 mass (PM25_MASS), PM10 mass (PM10_MASS), PM2.5-10 mass (PM_COARSE), and trace elements AL, CO, CU, FE, KP, MN, NI, SI, and VA. Frequency distribution of indoor concentrations of PM mass, PM chemical components, light-scattering, endotoxin, and fungal spores Frequency distribution of indoor concentrations of total pollens and selected polycyclic aromatic hydrocarbons (ACE, ANT, ACY, BAA, BAP, BGP, BBF, BKF, CRY, FLU, and FLT). Frequency distribution of indoor concentrations of selected polycyclic aromatic hydrocarbons (ICP, NAP, PYR, and PHE) and trace metals (Al, Fe, K, Mn, Ni, Pb, Si, and Va). Levels of Dust Mite Allergen (“Der-F” and “Der-P”)in Household Dust: Comparison of Homes with and without Carpet Levels of Cat allergen (“Fel-D”) in Housedust: Comparison of Homes with and without Cats Levels of Dog Allergen (“Can-F”) in Housedust: First Visit Samples Levels of Cockroach Allergen (“Bla-G”) in Housedust: Comparison of Homes with and without a History of Cockroaches Levels of Nicotine from Secondhand Smoke: Comparison of homes with and without smokers Levels of Nicotine from Secondhand Smoke inside Homes: Effect of “No Smoking Policy” Levels of Nitrogen Dioxide (NO2) inside Homes (ppb): Comparison of Homes with and without Gas Stoves Comparison of indoor and outdoor 24-hr concentrations of particulate matter at FACES residences Comparison of indoor and outdoor 24-hr concentrations of biological agents at FACES residences. Comparison of indoor and outdoor 24-hr concentrations of PM10 trace elements at FACES residences. Comparison of indoor and outdoor 24-hr concentrations of selected polycyclic aromatic hydrocarbons at FACES residences. Frequency distribution of indoor/outdoor concentration ratios of PM mass, PM chemical components, light scattering, endotoxin. and fungal spores. Frequency distribution of indoor/outdoor concentration ratios of total fungi, total pollens,

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4-81

4-82

4-83

4-84 4-108 4-109 4-110 4-111 4-112 4-113 4-114 4-115 4-116 4-117 4-124 4-125 4-126 4-127 4-131 4-132

4.1.6-1 4.1.6-2 4.1.6-3 4.1.6-4. 4.1.6-5 4.1.6-6 4.1.6-7 4.1.6-8 4.1.6-9 4.1.6-10 4.1.6-11 4.1.6-12 4.1.6-13 4.1.6-14 4.1.6-15 4.1.6-16 4.1.6-17 4.1.6-18 4.1.6-19 4.1.6-20 4.1.7-1 4.1.7-2 4.1.7-3

polycyclic aromatic hydrocarbons and selected trace metals (Al, Fe, K, Mn, Al, Si, and Va). Map of air quality monitoring locations, FACES residences, and roadways in Fresno Typical spatial distribution of 24-hr average PM2.5 and PM10 mass concentrations in FACES in the cool season; data shown are for 8 p.m. January 3 to 8 p.m. January 4, 2003 Spatial distribution of 24-hr average PM2.5 and PM10 mass concentrations in FACES in the cool season; data shown are for November 20-21, 2002; December 24-25, 2002; January 1112, 2003; and February 8-9, 2003. Spatial distribution of 24-hr average PM2.5 and PM10 mass concentrations in FACES in the warm season; data shown are for June 19-20, August 21-22, September 4-5, and October 78, 2002. Spatial distribution of 24-hr average PM2.5 NO3 and OC concentrations in FACES in the warm season; data shown are for 8 p.m. July 1 to 8 p.m. July 2, 2002. Spatial distribution of 24-hr average PM2.5 NO3 and OC concentrations in FACES; data shown are for February 20-21, March 20-21, June 22-23, and August 14-15, 2002. Spatial distribution of 24-hr average PM2.5 EC and SO4 concentrations in FACES in the cool season; data shown are for 8 p.m. January 1 to 8 p.m. January 2, 2003. Spatial distribution of 24-hr average PM2.5 EC and SO4 concentrations in FACES; data shown are for June 12-13, 2002; August 23-24, 2003; January 11-12, 2003; and February 89, 2003. Spatial distribution of 24-hr average concentrations of 15 trace elements in FACES on November 20-21, 2002. Iron (FE) concentrations are displayed as one-tenth their actual concentrations. Spatial distribution of 24-hr average concentrations of 15 trace elements in FACES on January 11-12, 2003. Iron (FE) concentrations are displayed as one-tenth their actual concentrations. Spatial distribution of 24-hr average concentrations of 13 PAHs in FACES on January 1112, 2003. Spatial distribution of 24-hr average concentrations of 13 PAHs in FACES on February 8-9, 2003 Mean spatial coefficient of variation in 24-hr concentrations of PM2.5 mass, NO3, OC, EC, SO4, PPAH, PM10 mass, PM2.5-10 mass, endotoxin, NO, NO2, NOx, CO, and ozone in Fresno in the warm season (top), cool season (middle), and annually (bottom). Error bars denote one standard deviation Mean spatial coefficient of variation in 24-hr PM10 elemental concentrations in Fresno. Error bars denote one standard deviation Mean spatial coefficient of variation in 24-hr PAH concentrations in Fresno Mean ratios of 24-hr average concentrations at schools, residences, and other air quality stations in the community to those at the central site stratified by direction from the central site in the cool season (top) and warm season (bottom). Bias in median ratios of 24-hr average concentrations at schools, residences, and other air quality stations in the community to those at the central site in Fresno. Bias in mean ratios of 24-hr average concentrations at schools, residences, and other air quality stations in the community to those at the central site in Fresno Relationship between freeway traffic indicators and the ratio of 24-hr average concentrations of PM2.5 mass, EC, OC, and phenathrene (PHE) at residences and schools to concentrations at the central site in Fresno with a few outliers removed for display purposes. Relationship between freeway traffic indicators and the ratio of 24-hr average concentrations of selected PAHs at residences and schools to concentrations at the central site in Fresno with a few outliers removed for display purposes. Range of estimated 8-hr daily maximum individual exposure concentrations for FACES subjects on days with panel studies from November 1, 2000, to March 31, 2003. Range of individual exposure, mean individual exposure, and central site concentrations of ozone (top) and NO2 (bottom) on days with panel studies from November 1, 2000, to March 31, 2003. Range of individual exposure, mean individual exposure, and central site concentrations of

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4-142 4-143 4-144 4-145 4-146 4-147 4-148 4-149 4-150 4-151 4-152 4-153 4-157 4-158 4-158 4-160 4-163 4-164 4-166 4-167 4-170 4-171 4-172

4.1.7-4 4.1.7-5 4.1.7-6 4.2.2-1 4.2.2-2 4.2.2-3 4.2.2-4 4.2.2-5: 4.2.3-1 4.2.3-2 4.2.4-1 4.2.4-2

PM2.5 (top) and EC (bottom) on days with panel studies from November 1, 2000, to March 31, 2003. Range of individual exposure, mean individual exposure, and central site concentrations of endotoxin (top) and coarse PM (bottom) on days with panel studies from November 1, 2000, to March 31, 2003. Range of individual exposure, mean individual exposure, and central site concentrations of alternaria (top) and agricultural fungi (bottom) on days with panel studies from November 1, 2000, to March 31, 2003. Range of individual exposure, mean individual exposure, and central site concentrations of cladosporium (top) and total pollen (bottom) on days with panel studies from November 1, 2000, to March 31, 2003. Time Series of Daily PM2.5 FEV1 and PM2.5 Time Series Ambient NO Time Series (ppb PERSONAL EXPOSURE EC TIME Series (µg/m3) NO2 Personal and Central Site (red) Data Structure Time Series for Estimated Personal and Ambient Exposure to NO2 Chladosporium and Agricultural Fungi for Panel Days Distribution of the acute response to 2-day lag NO2- Sum of Fixed and Random Effects Distribution of Chronic Response to Acute NO2 Effect – Sum of Fixed and Random Effects

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4-173 4-174 4-175 4-211 4-212 4-213 4-213 4-213 4-223 4-224 4-244 4-244

Glossary (NH4)2SO4 24-hr AADT ACCEPTABLE ACE ACY AG AGFG AIC AL ALTE AMB ANT ARB ART AS ASP ATS AU BA BAA BAA BAM BAP BBF BC BET BGP BIC BKF BlaG BR bsp BSVT CA CalTrans canF CD CEL CHA CHR CHS CL CLAD CO Co

ammonium sulfate 24-hour total annual average daily traffic volumes at least 2 acceptable FEV1 measurements acenapthene acenaphthylene Silver Agricultural fungi Akaike Information Criterion Aluminum Alternaria Ambrosia anthracene California Air Resources Board Artemesia Arsenic Aspergillus/Penicillium American Thoracic Study Gold Barium benz(a)anthracene Benz(a)anthracene beta-attenuation mass monitor benzo(a)pyrene benzo(b)fluoranthene black carbon Betulaceae benzo(ghi)perylene Bayesian Information criteria benzo(k)fluoranthene Cockroach allergen Bromine light scattering coefficient of particles Burkard Seven Day Recording Volumetric Spore Trap Calcium California Department of Transportation dog allergen Cadmium Celtis Chenopodiaceae/Amaranth chrysene Children’s Health Study Chlorine Cladosporium carbon monoxide Cobalt

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COPD Cr CRY Cu CUT CV DAG DAIB DBA DEP DIDTEST DLG DNA DR DRG DRI DSA EC EO ESRI ETA ETS EU FACES Fe FEF25-75 FEF75 felD FEV1 FLT FLU FO FRM FUSD FVC Ga G-comp GINA GIS grains/m3 GST HDV Hg HRMSM HVAC I/O IC ICP

chronic obstructive pulmonary disease Chromium Chrysene Copper Cupressaceae and Sequoia coefficient of variation directed acyclic graph “Data Adjusted for Instrument Bias” dibenz(a,h)anthracene diesel exhaust particles attempted an A.M. EasyOne session USGS Digital Line Graph deoxyribonucleic acid double robust estimator (MSM) diagnostic related group Desert Research Instititute deletion/substitution/addition algorithm elemental carbon EasyOne® Environmental Systems Research Institute, Inc. experimental treatment assumption Environmental Tobacco Smoke (also called SHS in this report) endotoxin units Fresno Asthmatic Children’s Environment Study iron forced expiratory flow between 25% and 75% of vital capacity forced expiratory flow at 75% of vital capacity cat allergen forced expiratory volume in 1 second fluoranthene fluorene field office federal reference method Fresno Unified School District forced vital capacity Gallium g-computation estimator (MSM) Global Initiative for Asthma geographic information systems grains per cubic meter glutathione s - transferase heavy-duty vehicle fraction of traffic Mercury history restricted marginal structural models Heating, ventilation and air conditioning indoor/outdoor ratio ion chromatography indeno(1,2,3-cd)pyrene

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ICS IDSW IDWT IDWTH IgE IL In

INFγ IPTW IQR ISAAC IUATLD JUG K KLARE KP La LA LAL LDV LIQ LPM MEDUSE MEMS MG µg/m3 µL µΜ MMAD Mn Mo MOR MSM NA NAP NAPCC NAPST NASCAUM NHLBI NHS Ni NO NO3 NOx NOy NP NRC NUC

inhaled corticosteroids inverse distance-squared weighted inverse distance-weighted traffic IDWT multiplied by HDV immunoglobin E interleukin Indium interferon-gamma inverse probability of treatment weight estimator (MSM) interquartile range International Study of Asthma and Allergies in Childhood International Union Against Tuberculosis and Lung Disease Average Carya and Juglans Potassium Kineteic Limulus Assay with Resistant-parallel-line Estimation Potassium Lanthanum Lanthanum Limulus amebocyte lysate light-duty vehicle fraction of traffic Liquidambar liters per minute rescue medication use in 1-hour before A.M. test (see Rmed) Microenvironmental Exposure Monitoring System Magnesium (qualitative only) micrograms per cubic meter microliters micrometers mass median aerodynamic diameter manganese Molybdenum Morus marginal structural models Sodium (qualitative only) naphthalene Napthalene from Chemcombs Napthalene concentration from Sorbent Tubes Northeast States for Coordinated Air Use Management National Heart Lung and Blood Institute Nurses Health Study Nickel nitrogen oxide nitrate oxides of nitrogen Reactive nitrogen particle number National Research Council no unmeasured confounding assumption

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O3 OC OLE OS P PAH Pb Pd PEFR PH PHE PIS PLA PM PM1 PM10 PM2.5-10 PM2.5 PMPAH POA PPAH ppb pphm ppm pRmed PTEAM PYR QA QC QUE Rb RH RMed ROS S SAS Sb Se SHS Si SJV SJVAQMD Sn SO2 SO4 SOPs spores/m3

ozone organic carbon Olea, Fraxinus, and Ligustrum oxidative stress Phosphorous polycyclic aromatic hydrocarbon Lead Palladium peak expiratory flow rate Phosphorous phenanthrene Pistacea Platanus particulate matter particulate matter with a mass median aerodynamic of 1 micron or less particulate matter with a mass median aerodynamic of 10 microns or less particulate matter with a mass median aerodynamic between 2.5 and 10 microns (coarse fraction) particulate matter with a mass median aerodynamic of 2.5 microns or less particulate matter polycyclic aromatic hydrocarbons Poaceae (including Cerealea) particle-bound polycyclic aromatic hydrocarbons parts per billion parts per hundred million parts per million rescue medication use 1 hour before evening sesion Particle Total Exposure Assessment Methodology pyrene quality assurance quality control Quercus Rubidium relative humidity rescue medication use in 1-hour before A.M. test reactive oxygen species Sulfur Statistical Analysis System software Antimony Selenium secondhand smoke silicon San Joaquin Valley San Joaquin Valley Air Quality Management District Tin sulfur dioxide sulfate standard operating procedures spores per cubic meter

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Sr SRA STI SU T TAMN TAP TC Ti Tl TNF-α TOP TOTFS U ULZ UR VA VOC WD WHO WIM WS XAD Y YT Zn Zr

Strontium sequential randomization assumption Sonoma Technology, Inc. Sulfur temperature TeleAtlas MultiNet™ USA triethylamine phosphate total carbon Titanium Thallium tumor necrosis factor alpha Total Pollen Grain Total fungal spores Uranium Ulmus/Zelkova Uranium Vanadium volatile organic carbons wind direction World Health Organization weigh-in-motion sensors wind speed polystyrene-divinyl benzene Yttrium Yttrium Zinc Zirconium

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1-1

1. EXECUTIVE SUMMARY 1.1

PROJECT OVERVIEW

1.1.1

Background and Public Health Significance

Children, especially children with asthma, have long been recognized by air pollution control agencies as a population at particular risk of suffering the adverse effects of air pollution exposure. While there remains debate as to whether air pollution alone can cause asthma, there is no debate regarding the role short-term exposures to various air pollutants have in the exacerbation of asthma in people diagnosed with the disease. Among the pollutants that have received the most attention in recent years is particulate matter (PM). However, there is a paucity of data on which components of the complex PM mixture produce these effects and no data on the relationship between the responses to short-term-exposures and the long-term progression of asthma in children. Furthermore, few studies have specifically looked at the effects of PM in the context of the complex exposures people experience outdoors and indoors – exposures that include not only other pollutants, but biologically active agents such as endotoxin, fungal spores, pollens, and common indoor allergens. Asthma is an airway disease, which is characterized clinically by reversible airway obstruction, non-specific airway hyperresponsiveness, and mucus secretion. Particulate and gaseous air pollutants contribute significantly to asthma burden by causing acute asthma-related symptoms and short-term declines in lung function. However, an effective public health policy to protect asthmatics from the acute adverse effects of air pollution, especially PM, has not yet been achieved due to insufficient information on which components of PM or other pollutants, at what concentrations and in what combinations are associated with which observed effects. Evidence is mounting that a key mechanism by which air pollutants and other airborne agents can adversely impact health is through the promotion or induction of oxidative stress and/or inflammation. Because a cardinal feature of asthma is persistent airway inflammation, it is biologically plausible that repeated exposures to oxidant pollutants, including components of PM, can lead to enhanced inflammation and more severe asthma. A better understanding is needed of the characteristics, both biological and exposure, that define subgroups of persons with asthma who are more/less acutely responsive to different pollutants, or who experience larger chronic effects associated with long-term exposures. The Fresno Asthmatic Children’s Environment Study (FACES) is focused on the determination of the effects of particulate matter (PM) air pollution, in combination with other ambient air pollutants and bioaerosols, on the natural history of asthma in young children who reside in Fresno, California. This community is notable for a high prevalence of asthma among an ethnically diverse population, and for high levels of ambient air pollution, especially PM, making it an appropriate location to address questions of air pollution’s impact on this vulnerable population. A unique opportunity to address critical questions related to air pollution’s effects on the long-term progression of asthma was presented by the U.S. EPA’s enhanced air quality monitoring platform (“Supersite”) in Fresno. This is the first, and to our knowledge, the only 1-2

study to date to investigate directly the relationship between adverse short-term air pollution health effects and the long-term progress of asthma. Consideration of all particle effects is in the context of the complex and seasonal patterns of air pollution mixtures, including bioaerosols, to which children are exposed. The study was comprised of two fully integrated components: an epidemiological and clinical component and an exposure assessment component formerly referred to as Part A and Part B, respectively. The overall study was designed as a 66-month effort, including a 6-month protocol refinement period. The ARB agreed to fund the project in two project periods (36 months and 30 months), with the second period of funding being contingent on satisfactory progress during the first. This report provides detailed information on the work completed to date, both in the characterization of the pollutant exposures of the asthmatic children that have been recruited for the study and the assessment of the effect of these exposures on lung function. 1.1.2

Study Goal, Research Questions and Hypotheses

The overall goal of FACES was to investigate the effects of PM air pollution on the natural history of asthma in young children. To achieve this goal, the study was designed to address four key research questions: 1. What is the relationship between short-term exposures to specific size fractions or constituents of particulate air pollution, or other ambient air pollutants, and acute exacerbations of asthma, which may include changes in lung function, occurrence of symptoms, and usage of medications? 2. What are the critical exposures leading to the observed acute health effects? For example, at what concentrations are the effects occurring, is there an interaction with other outdoor and indoor pollutants (criteria pollutants, toxic air contaminants) or bioaerosols (pollens, spores, PM-associated endotoxins), and what specific sources of PM are more strongly associated with specific adverse effects? 3. Are there cumulative effects of repeated acute responses to short-term air pollution exposures that result in altered disease progression, e.g., asthma severity, or changes in other markers of health status, e.g., reduced lung function “growth”? 4. Among the general population of asthmatic children, what are the biologic characteristics (e.g., asthma severity, , nutrition) or exposure characteristics (e.g., activity patterns, housing characteristics) that define subgroups who are more (or less) responsive to given acute exposures, or who experience larger effects associated with long-term exposures? The health-related hypotheses developed to address these questions and presented in our orginal application for funding were the following: Short-term Effects: Hypothesis 1: Chemical components of particle air pollution (PM) that have immuno-enhancing properties (i.e., polyaromatic hydrocarbons (PAH) in diesel exhaust) are associated with symptom onset and severity and short-term reductions in lung function in a seasonally dependent pattern. 1-3

Hypothesis 2: There are specific biologic components (e.g., endotoxin, fungal spores) and specific anthropogenic components (e.g., latex particles from road tire dust) in the PM2.5-10 (coarse) fraction that are associated with exacerbations of symptoms and short-term, reversible decrements of lung function in a subset of asthmatic children and these associations are strongest during the months of April through September, when PM2.5-10 constitutes a major fraction of the PM10 mass. Hypothesis 3: Components of PM that are markers for the oxidative potential of PM (e.g., transition metals) are associated with more severe symptoms and short-term, reversible decrements in lung function in a subset of asthma children. Medium-Term Effects (Expected over Four Years of observation): Hypothesis 4: The subsets of asthmatic children who respond with short-term deficits in lung function to components of PM (alone and/or in conjunction with other ambient air pollutants) will show relatively slower age-sex-specific growth of lung function than asthmatic children who do not so respond. Hypothesis 5: The subset of asthmatic children who respond either to the immuno-adjuvants in PM or the oxidizing properties of PM will have greater asthma-related morbidity {increased frequency and severity of attacks of asthma, more likely to be classified as severe asthma (e.g., NHLBI/WHO classification), and have more medical interventions (e.g., increased use of quick relief medications, higher doses of anti-inflammatory medication, need for medical care). 1.2

METHODS

1.2.1

Study Design and Population

To test the health-related hypotheses our study design includes two components: 1) a series of panel-studies, which allows an assessment of short-term (daily) exposure effects that occur in seasons with different air pollution and meteorological patterns, and; 2) a classical longitudinal component that allows an assessment of changes due to the cumulative effects of short-term-exposure-responses. The original goal was to recruit up to 450 asthmatic children (ages 6-10 at enrollment) in nine months in Year 1. Shortly after their baseline examinations, children would participate in a 14-day panel involving daily follow-up. In Year 2, the children would participate in a 14-day health-monitoring period in each of three air pollution seasons, for each of the 3½ years of follow-up. For the longitudinal study component, all children would undergo detailed evaluations at baseline and every 6-months thereafter. Because of unanticipated difficulties in recruitment of asthmatic children, with approval from ARB, the original goal of 450 subjects was revised to 300 subjects (up to age 11 at enrollment). Recruitment continued through October 2004. By the close of recruitment, 315 children participated in the study. It is not believed that the above noted changes significantly impacted the ability to meet the study objectives, in that 1-4

both the size of the cohort and the number of follow-up observations accumulated already are larger than most published studies that have reported associations with air pollution and symptoms or reduced lung function. 1.2.2

Health Assessment

The primary health outcomes to evaluate the day-to-day impacts of air pollution include: asthma symptoms (e.g., wheeze, cough, etc.); lung function (e.g., forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and asthma medication use (a covariate in some analyses). Longer-term health outcomes of primary interest include: changes in classification of asthma severity over the study period; and changes in levels of lung function over the study period (“growth” of lung function). As noted above, the panel component of the study involved the observation of children during 14-day panels. Participants were asked to provide daily data, including twice-daily (a.m. and p.m.) lung-function tests, symptoms, medication use, and information to determine locationtime-activity patterns. The longitudinal component involved subject visits to the field office to undergo detailed evaluations at baseline and every 6-months that included a medical history, housing characteristics, medication use, lung function tests, allergen skin testing (at least once over the study period), dietary assessment (preferably twice, once in the warm season and once in the cool season), and measures of somatic growth. Beginning 3-months after baseline, then every 6 months thereafter, adults were asked about their child’s symptoms, medication use and any changes to housing characteristics. A large number of data collection procedures and instruments (such as eligibility screening, baseline and follow-up questionnaires, daily diary, home environment survey forms) were developed specifically for FACES. Where possible, we used or adapted instruments from other studies, including the Southern California Children’s Health Study (CHS), National Cooperative Inner-City Asthma Study (NCICAS), the Nurses Health Study and the Harvard Six-City Study. Extensive effort went into evaluation of appropriate portable and clinic-based spirometers. The latter needed to serve as a “gold standard” that would allow comparisons among the children across time and between FACES and other studies, such as the CHS. This work has now been published (1). Also developed was a strategy for classifying asthma severity, which is an important outcome for the longitudinal component of FACES. Asthma severity is an important determinant of both short-term and long-term responses of asthmatic children to air pollution exposures, and repeated exposures-responses in turn influence asthma severity. However, asthma severity is difficult to disentangle from asthma control and existing classification schemes commonly used in the clinical setting are not designed to isolate underlying asthma severity over the long-term. Therefore, we needed to develop a strategy suitable for an epidemiologic study of the effects of environmental exposures among a pediatric population. After evaluating a number of strategies, a multi-component approach was developed that adapts existing asthma severity classification schemes. This work has been submitted for publication.

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1.2.3

Exposure Assessment

Central to the core study design and ultimately to the success of FACES, is the need to accurately define the exposure-response relationship(s) for each air pollutant of interest, with consideration of co-exposures. An underlying premise of FACES is that observed health effects are associated with specific exposures or sets of exposures, and that there are subsets of the population of asthmatic children who are more/less responsive to different exposures. To identify these subsets of children, and to define the exposure characteristics of the children who comprise the subsets, the exposure assessment program is targeted to accurately estimate the individuallevel exposures. Thus the technical approach for exposure analysis is to build databases and models to generate individual exposure estimates, rather than community average exposure estimates. The individual-level, or personal exposure estimates are based on microenvironmental models adjusted for indoor, outdoor, and activity patterns. Resources were not available for making direct measurements of personal exposures; these would have enhanced the exposure models but are not critical to their development. The selection of environmental factors to be measured in FACES was based on the project’s health hypotheses. The air pollutants measured included: PM mass and chemical constituents of coarse and fine fractions, particle number for PM in the ultrafine size range (
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