Presentation on theme: "2005 April 13 1 Are peak expiratory flow rates of asthmatics impaired by levels of SO 2 in the EPA 'safe' zone? The project was reviewed and approved by."— Presentation transcript:
2005 April 13 1 Are peak expiratory flow rates of asthmatics impaired by levels of SO 2 in the EPA 'safe' zone? The project was reviewed and approved by the University of Medicine and Dentistry of New Jerseys Institutional Review Board for human subject research at Robert Wood Johnson Medical School & New Jersey Medical School.
2005 April 13 2 April 13, 2005 Presented to the NJ CLEAN AIR COUNCIL April 13, 2005 PUBLIC HEARING on "Air Pollution - Effects on Public Health, Health Care Costs and Health Insurance Costs" by Stanley H. Weiss, MD
2005 April 13 3 The full study report is currently draft and is undergoing review by the New Jersey Department of Environmental Protection (DEP) Division of Science Research & Technology (DSR) Bureau of Environmental Health Science and Environmental Assessment. A final report will be provided to the DEP following receipt and responses to any comments. The report has already been reviewed by DSM.
2005 April 13 4AUTHORS Stanley H. Weiss, MD 1,2,3 Azadeh Tasslimi, BA 1 Amy Davidow, PhD 1 Kathy Belby, RN 1 Shahnaz Alimokhtari, MS 4 Clifford P. Weisel, PhD 2,3,4 (1)Department of Preventive Medicine and Community Health, UMDNJ – New Jersey Medical School, 30 Bergen St, Suite ADMC 1614, Newark, NJ 07107, 973-972-4623 email@example.com@umdnj.edu (2) UMDNJ School of Public Health (3) Co-Principal Investigators (4) Environmental and Occupational Health Sciences Institute, UMDNJ – EOHSI/RWJMS, 170 Frelinghuysen Rd, EOHSI 3-314, Piscataway, NJ 08855.
2005 April 13 5 PURPOSE Determine if changes in Determine if changes in peak flow expiratory flow rate (PEFR) among asthmatic school children were related to air pollution from sulfur dioxide (SO 2 ).
2005 April 13 6 SETTING 3 Rural communities in Warren County, NJ (Northwestern NJ) 1. Belvidere 2. White Township 3. Harmony Township
2005 April 13 8 School Surveys Fall 2002 A survey of asthma symptoms was conducted of all students with the cooperation of the public schools in the community. In conjunction with review with the school nurses and related f/u, these data were used to determine the actual pediatric and adolescent asthma rates by age, gender and other parameters. Hierarchical estimates of prevalence for the 1641 students (K-12) were: Physician-diagnosed, Current Asthma11% Undiagnosed Current Respiratory Symptoms, that can be consistent with asthma 11%-18% Physician-diagnosed Asthma, no current symptoms 7%-11% No Evidence of Asthma 57%-71%
2005 April 13 9 PROSPECTIVE STUDY FEBRUARY – JUNE 2003 ELIGIBILITY for ENROLLMENT: All Physician-Diagnosed Asthmatic students enrolled in the public school systems of Belvidere, White Township and Harmony Townships and in grades 5 through 12, who had asthma symptoms during the prior year or had prescription medicine for asthma
2005 April 13 10 WEB-BASED QUESTIONNAIRE GOAL: Capture All Relevant Information & Minimize # Of Questions Asked In Order To Maximize Participation & Compliance Rate COMPONENTS (SYMPTOMS AND POTENTIAL MODIFIERS): 1.General Health, 2.Prevalence & Severity Symptoms Related to Asthma & Resp Problems, 3.Measurement of Peak Expiratory Flow Rate 4.Medication Use, 5.Encounters w/ Potential Triggers of Asthma (i.e. smoke, animal fur, etc) DESIGNED WITH PULL-DOWN MENUS SO THAT IT COULD BE COMPLETED ON A DAILY BASIS AND TAKE LESS THAN 10 MINUTES
2005 April 13 11 AIR-MONITORING SITES AIR POLLUTION LEVELS were collected continuously at 3 MONITORING STATIONS : SULFUR DIOXIDE (SO 2 ) SULFUR DIOXIDE (SO 2 ) Emitted by Coal-powered plants in the area Known respiratory irritant PARTICULATE MATTER BELOW 2.5 microns (PM 2.5 ) PARTICULATE MATTER BELOW 2.5 microns (PM 2.5 ) Emitted by combustion processes & formed in atmosphere Suggested to be linked to cardiovascular & respiratory ailments OTHER AIR POLLUTANTS OTHER AIR POLLUTANTS (Volatile Organic Compounds - VOCs) (Volatile Organic Compounds - VOCs) Data collected periodically on 70 VOCs, but limited number of measurements
2005 April 13 12 STUDY PARTICIPANTS: 51% (64/125) of asthmatic students (physician-diagnosed), grades 5-12, were eligible and then gave informed consent to participate *Higher participation rate in the elementary and middle school than in the high school. RECRUITMENT INTO STUDY ON ROLLING BASIS: Start - January 30, 2003 Last student accepted into the study - May 6, 2003 All students were asked to continue to enter data until June 19, 2003. Thus, the potential number of days of data entry varied from 45 to 141 days. PROSPECTIVE STUDY
2005 April 13 13 TOTAL # OF STUDENT-DAYS ON WHICH SYMPTOMS, MEDICATIONS, AND PEFR ENTERED= 4,777 TOTAL # OF STUDENT-DAYS ON WHICH W/ SYMPTOMS & MEDICATIONS, BUT NO PEFR ENTERED= 824 TOTAL NUMBER OF STUDENT-DAYS ON WHICH SYMPTOMS & MEDICATIONS WERE ENTERED BY PARTICIPANTS=5,601 DATA COLLECTED
2005 April 13 14 Data Exclusions 3 subjects were dropped from analysis who had completed the web-based survey on less than 14 days. Data Monitoring during the course of the study suggested that 1 subject had unreliable data; he was contacted during the course of the study and he could not resolve critical inconsistencies. Inconsistencies noted for other students were all satisfactorily resolved. This left 60 subjects for analysis.
2005 April 13 15 STATISTICAL ANALYSIS One monitoring site was at Belvidere HS. Initial statistical analysis was performed using Belvidere residents only, since SO2 was directly measured in their town. Examined PEFR –Objective measure of respiratory function –Continuous values, which offers analytic advantages Examined medication use –ongoing/prophylactic/in response to problem Developed mixed model
2005 April 13 16 MIXED MODEL How much the change in peak flow rate is related to other changes (pollution, temperature, and other factors) Controls for each individual subject **This is an advantage because PEFR varies with a number of physiological variables, in particular, height, weight, age, & gender (1-6) Outcome = Natural Logarithm (ln) of PEFR Method = Mixed Model with a Random (Subject-level) Effect
2005 April 13 17 MIXED MODEL Variables included in Stepwise Assessments: Daily and daytime (6am-8pm ) - maximum and mean: hourly & 5-minute SO2 mean SO2 (linear & non-linear terms) same day, 1- and 2-day lagged SO2 peak and mean same-day, and mean lagged, PM2.5 Above data are from each of the 3 monitoring stations mean daytime (7am-6pm) temperature age, gender same-day medication use (controller) pollen (trees, grass, weeds, mold)
2005 April 13 18 Best Fit for Model PEAK 5-MINUTE DAYTIME (6AM-8PM) SO2 from Belvidere MEAN PRIOR DAY SO2 from Belvidere DAYTIME TEMPERATURE (7AM-6PM)
2005 April 13 19 Same effect of SO 2 seen for White Township students; –Consistent with the Belvidere monitoring station being between a major source of SO2 & White Twp No statistical association for students in Harmony Township –Harmony in a different direction from the Belvidere monitor –other monitoring site also not appropriate for exposure characterization for Harmony residents Harmony Twp residents who attend Belvidere HS were included in model Model applied to White & Harmony using Belvidere HS SO 2 Data
2005 April 13 20 FULL MODEL RESULTS DESCRIPTION OF STUDY PARTICIPANTS HARMONY TWP HS STUDENTS - 4 WHITE TWP STUDENTS- 16 BELVIDERE STUDENTS-27 TOTAL IN FULL MODEL ANALYSIS-47 FEMALES - 28 (60%): MALES - 19 (40%) Age Mean - 13 yrs Range - 9-19 yrs Median - 13 yrs
2005 April 13 21 SO 2 values in Belvidere: Ranged up to - 21 ppb for Daily Mean SO 2 21 ppb for Daily Mean SO 2 On 16 (11%) of 141 days, On 16 (11%) of 141 days, the daily mean SO2 was >ppb the daily mean SO2 was > 10 ppb 331 ppb for 5-minute Daytime Peak SO 2 On 14 (10%) of 141 days, the peak 5-minute SO2 was > 100 ppb The effect on Peak flow on reaching these 2 levels of SO2 are displayed on the next slide…
2005 April 13 22 CoefficientP-Value%Reduction in PEFR 5-minute Daytime (6am-8pm) MaximumSO2-0.069320.0071-0.69% For a 100 ppb increase in SO2 Prior Day Mean SO2 -1.14340.0004-1.1% For a 10 ppb increase in SO2 Results of Final PROC Mixed Model With All 47 Subjects
2005 April 13 23 The total variability among the peak flow rates was not the same for all students; the studys statistician examined the contribution of each of the 47 students to the model The statistical association between SO 2 levels and peak flow rates appeared to vary with individuals – 2 students appear highly sensitive to SO 2 –33 students appear to be somewhat sensitive to SO 2 –12 students appear not to be sensitive to SO 2 Analyses were conducted to determine which subjects contributed particularly to the observed associations
2005 April 13 24 CoefficientP-Value % Reduction in PEFR Very Sensitive Subjects (n=2) SO2 5-minute Daytime Max -0.3174<0.0001-3.1% For a 100 ppb increase in SO2 SO2 Prior Day Mean -5.9878<0.0001-5.8% For a 10 ppb increase in SO2 SomewhatSensitive Subjects (n=33) SO2 5-minute Daytime Max -0.072860.0326-0.73% For a 100 ppb increase in SO2 SO2 Prior Day Mean -8.73200.0404-0.87% For a 10 ppb increase in SO2 Post-hoc sub-group Multivariate analyses
2005 April 13 25 Student A – Bivariate Display of Data Belvidere resident, grade 7, male
2005 April 13 26 Student B – Bivariate Display of Data White Twp resident, grade 5, male
2005 April 13 27 Association between Mean Prior-Day SO 2 and PEFR This model predicts overall for the 47 students, that for a 10 parts per billion (ppb) increase in prior-day mean SO 2 there is an average decrement in PEFR of 1.1%. For the 2 most sensitive students, this effect was roughly 6 times greater (-5.8%), and this magnitude of effect could be of clinical significance.
2005 April 13 28 This model predicts overall for the 47 students, that for a 100 ppb increase in peak same-day SO 2 there is an average decrement in PEFR of 0.69% For the 2 most Sensitive Students, this effect was nearly triple (-3.1%). Association between Max Same-Day SO2 & PEFR
2005 April 13 29 CURRENT FEDERAL GUIDELINES SO 2 Air Quality Standards A guideline has been proposed by the US Environmental Protection Agency (EPA), based on the conclusion that in some localized situations, 5-minute SO2 concentrations above 1600 µg/m3 might pose a health threat to sensitive individuals. [Draft Guideline Document for Ambient Monitoring of 5-Minute SO2 Concentrations, EPA, Office of Air Quality Planning and Standards, Research Triangle Park, NC, July 20, 2000; see also http://airqap.com/monitoring/Benchmarks%20for%20SO2%20&%20 PM25.htm ]. http://airqap.com/monitoring/Benchmarks%20for%20SO2%20&%20 PM25.htm This corresponds to an average over the five minutes of 615 ppb.
2005 April 13 30 CURRENT FEDERAL GUIDELINES SO 2 Air Quality Standards Most air pollution monitors measure the amount of pollution in the air on almost a continuous basis. Current guidelines assume that higher levels of pollution can be tolerated without effect for short periods of time. Thus, the National Ambient Air Quality Standards have an averaging time as well as a concentration associated with them. Typically, the longer the averaging time is, the lower is the level of the standard. The averaging times utilized in development of standards represent simplifications of a more complicated statistic. Refer to 40 CFR Part 50 (in the Code of Federal Regulations) for guidance on how the standard are required to be computed for regulatory purposes.
2005 April 13 31 SUMMARY We observed significant effects on peak flow rate at levels well below the federal 24 hour standard (mean daily value) for SO 2 of 140ppb, which had been set to deal with short term effects in the overall population. Some asthmatics appear to be especially sensitive to SO 2. Relatively low levels of SO 2 had a magnitude of effect on respiratory function that raise clinical concern. Our data suggest that even more transient exposure, to levels far below this guideline, may pose a health threat to sensitive individuals. Further analyses to examine asthma symptoms are in progress.
2005 April 13 32 LIMITATIONS The grouping of which students were most sensitive to SO2 was determined through data analysis, not a priori. Thus, further follow-up may be useful to prospectively assess whether the same students remain sensitive. However, if medication regimens change, this might affect sensitivity. Modeling to incorporate medication changes may be useful, but will be complicated.
2005 April 13 33 LIMITATIONS The statistical association does not rule out that the effect is due to an unmeasured factor that correlates with both SO 2 and peak flow. The study was conducted in a single region, and thus cannot be assumed to necessarily generalize to other communities.
2005 April 13 34 RECOMMENDATIONS Given that some persons may be especially sensitive to SO 2, the definition of what constitutes a safe level may need to be revised. Some asthmatics may need to be especially cognizant of SO 2 pollution in their region and may need to attempt to modify their exposure when levels are high.
2005 April 13 35 Acknowledgements Supported in part by grants from Roche Vitamin (DSM) Inc through the SEP Mechanism of NJ Department of Environmental Protection - see also http://dsmcap.com/http://dsmcap.com/ Students & their families who took time to make the entries Special thanks are due to Beecher Zollinger, MD and the school nurses Jill Broscius, RN, Lynn Serniuk, RN, Lois Hampshire, RN, and Donna Golda, RN.
2005 April 13 36 References (1)Knudson RJ, Slatin RC, Lebowitz MD, Burrows B. The maximal expiratory flow- volume curve. Normal standards, variability, and effects of age. Am Rev Resp Dis 1976; 113:587-600. (2)Quackenboss JJ, Lebowitz MD, Krzyzanowski M. The normal range of diurnal changes in peak expiratory flow rates. Am Rev Resp Dis 1991; 143:323-330. (3) Krzyzanowski M, Quackenboss JJ, Lebowitz MD. Peak expiratory flow rates and symptoms to ambient ozone. Arch Environ Health 1992; 47(2):107-115. (4)Chiang ST, Han TS. Peak flow rate in relation to age, sex, and anthropometric measurements. Acta Paediatr Scand 1965; 54:439-445. (5)Hegewald MJ, Capo RO, Jensen RL. Intraindividual peak flow variability. Chest 1995; 107(1):156-161. (6) Polgar G, Promadhat V. Standard Values: Peak expiratory flow rates and normal values. Pulmonary function testing in children: Techniques and standards. Philadelphia: W.B.Saunders Company, 1971. Pages: 188-194.
2005 April 13 37 Related Presentations from this Study 1. Tasslimi A, Weisel CP, Belby K, Morales L, Lee N, Weiss SH. Apparent prevalence of adolescent asthma: impacts of asthma definition and sources of information. The 8th Annual Public Health Symposium, held at Rutgers University, Piscataway, NJ, April 7, 2003. 2. Diamond AC, Weisel CP, Lee N, Weiss SH. Design and implementation of an Internet- based questionnaire for daily ascertainment of asthma status in a prospective study. The 8th Annual Public Health Symposium, Rutgers University, Piscataway, NJ, April 7, 2003. 3. Diamond AC, Weisel CP, Lee N, Weiss SH. Design, implementation and monitoring of Internet-based prospective data collection in an epidemiologic study of asthma and the environment. Research Symposium on Genomics, Proteomics, Pharmacogenomics and Bioinformatics. Robert Wood Johnson Medical School, Piscataway, NJ, May 9, 2003. 4. Weiss SH, Tasslimi A, Lee N, Alimokhtari S, Morales L, Hom HL, Weisel CP. Understanding the prevalence of asthma in a community: Impacts of study design and definition. The 131st Annual Meeting (November 15-19, 2003) of the American Public Health Association, San Francisco, Session 4262.0 [Tues, Nov 18, 2003], Abstract #60074.The 131st Annual Meeting (November 15-19, 2003) of the American Public Health Association 5. Weisel CP, Weiss SH, Tasslimi A, Diamond A, Alimokhtari S. Use of a web-based questionnaire to collect exposure and symptom data in asthmatic adolescents [abstract]. In: Abstract Book - 14th Annual Conference of the International Society of Exposure Analysis; 2004 Oct 17-21; Philadelphia, PA. Platform W2C Exposure and Health Interface; Abstract number W2C-03; p 290. 6. Weiss SH, Tasslimi A, Davidow AL, Weisel CP. Are peak expiratory flow rates of asthmatics impaired by levels of SO2 in the EPA 'safe' zone? The 132nd Annual Meeting (November 2004) of the American Public Health Association, Washington DC, Session 3118.0: Monday, November 8, 2004 (oral).Are peak expiratory flow rates of asthmatics impaired by levels of SO2 in the EPA 'safe' zone? The 132nd Annual Meeting (November 2004) of the American Public Health Association
2005 April 13 39 ADVANTAGES IN USING A WEB-BASED QUESTIONNAIRE
2005 April 13 40 POTENTIAL ADVANTAGES PAPER VERSION Administration of daily questionnaires can be time and labor intensive, paper needs periodic retrieval WEB BASED Web based system accessed by participate at his/her convenience, entry often faster, contact with staff minimized
2005 April 13 41 PAPER VERSION Compliance, particularly for children/adolescents, is often low for daily questionnaires Compliance rate unknown until attempting to retrieve data WEB BASED Children/adolescents are on computers daily so smaller intrusion in their lives Compliance checked in real time POTENTIAL ADVANTAGES
2005 April 13 42 PAPER VERSION Paper questionnaires require subsequent entry with associated transcription errors WEB BASED Data is directly added to data base, minimal errors Checks can be made to restrict to valid entries Data can be reviewed quickly so participants can be contacted for questions POTENTIAL ADVANTAGES
2005 April 13 43 SURVEY INSTRUMENT Section 1 (28 questions) Details on symptoms, triggers, location and peak flow rate Each includes time of day & duration Each includes time of day & duration Section 2 Details on medication taken Amount and time of day Picklist and check box entries Entry for current and previous two days permitted Stop & restart after each major section possible
2005 April 13 44 The home page contains a login, relevant links, important announcements, and information. These are changed periodically.
2005 April 13 45 SYMPTOM SECTION Tracking of individual health and asthma related symptoms along with when problems occurred Exposure to asthma triggers (smoke, allergens, animal, etc) What microenvironments visited Peak flow rates (up to 4 values) Summary verification provided before saving Internal checks for general and specific symptoms
2005 April 13 47 MEDICAL USE SECTION Comprehensive medication tracking includes time of intake and dosage A users medications are chosen from a medication database A users medications are chosen from a medication database (contains over 200 medications, both prescription and over the counter, characterize by type). Checks for medicine combinations and dosage that are not medically advisable
2005 April 13 49CONCLUSIONS Web Based Questionnaires are feasible for daily entry from adolescent and children (grades 4 – 12) – data from 64 students over 2 – 4 months obtained Web Based Questionnaires are feasible for daily entry from adolescent and children (grades 4 – 12) – data from 64 students over 2 – 4 months obtained Real time monitoring can help improve compliance and quality Real time monitoring can help improve compliance and quality When combined with telephone/ e-mail reminders and incentives When combined with telephone/ e-mail reminders and incentives
2005 April 13 50 CONCLUSIONS (continued) Data entry errors are greatly reduced Data entry errors are greatly reduced Entry can be more rapid than paper – (only 5 – 10 minutes per day required) Entry can be more rapid than paper – (only 5 – 10 minutes per day required) Has potential for use in large epidemiological studies for population who typically access computer Has potential for use in large epidemiological studies for population who typically access computer
2005 April 13 51 PILOT STUDY 10 students, grades 5-12, with physician-diagnosed asthma, were enrolled in a Pilot Study to: 1) Verify that web site functioned correctly 2) Verify accuracy of Data Collection 3) Elicit feedback from students to improve Site for ease of entry 4) Field-tested Baseline Questionnaire that ascertained the general health of the subjects and their medication; medication data were used to individualize the web questionnaire for each subject.
2005 April 13 52 Confirmation of Validity of Survey Responses All data were first reviewed to verify that no inconsistencies existed in the input that might have resulted from either inadvertent or intentional errors. Each subjects responses were plotted chronologically to examine trends in the data and for individual data points that differed from the previous and next days data.
2005 April 13 53 Least Sensitive Subjects ( n=12 ) CoefficientP-value SO2 5-minute Daytime Maximum 0.006307NS SO2 Prior Day Mean -0.00048NS Post-hoc Sub-group Multivariate Analyses of the Least Sensitive Subjects
2005 April 13 54 MIXED MODEL Accounts for different number of repeat measurements made on each individual Implements random effects in a statistical model framework & permits modeling the covariance structure of the data It can compute efficient estimates of fixed effects and valid errors estimates within the Generalized Linear Modeling (GLM) procedure. It is important to model the covariance structure for repeated measures data because measurements taken close in time are often highly correlated. A log transformation of the peak flow rate was done so that the dependent variable of the GLM was close to normally distributed.