Are peak expiratory flow 

rates of asthmatics impaired 

APHA 2004 

Annual 

Meeting

Session 

#3118.0 

Paper #83634

rates of asthmatics impaired 

by levels of SO2in the EPA 

'safe' zone?

***The project was reviewed and approved by the University of Medicine and Dentistry of New Jersey’s 

Institutional Review Board for human subject research at Robert Wood Johnson Medical School and New Jersey 

Medical School.
Authors

Stanley H. Weiss, MD 1,2

Azadeh Tasslimi, BA 1 - Presenter

(tassliaz@umdnj.edu)

Amy Davidow, PhD 1

Kathy Belby, RN 1

Shahnaz Alimokhtari, MS 3

Clifford P. Weisel, PhD 2,3

(1) Dept. of Preventive Medicine and Community Health, 

UMDNJ – New Jersey Medical School, 30 Bergen St, Suite ADMC 1614, 

Newark, NJ 07107, 973-972-4623, 

(2) NJ School of Public Health, 

(3) Environmental and Occupational Health Sciences Institute, 

UMDNJ – EOHSI/RWJMS & NJ School of Public Health, 

170 Frelinghuysen Rd, EOHSI 3-314, Piscataway, NJ 08855.
Purpose

Determine if changes in 

peak flow expiratory flow rate (PEFR) 

among 

asthmatic school children 

were related to 

air pollution from 

sulfur dioxide (SO2).
SETTING

3 Rural communities in 

Warren County, NJ (Northwestern NJ)

1. Belvidere 

2. White Township 

3. Harmony Township
WARREN COUNTY, NJ
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 Asthma” 11%

“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%
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
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
AIR-MONITORING SITES

AIR POLLUTION LEVELS were collected continuously at 

3 MONITORING STATIONS:

SULFUR DIOXIDE (SO2) 

Emitted by Coal-powered plants in the area

Known respiratory irritant

PARTICULATE MATTER BELOW 2.5 microns (PM2.5)

Emitted by combustion processes & formed in atmosphere

Suggested to be linked to cardiovascular & respiratory ailments

OTHER AIR POLLUTANTS 

(Volatile Organic Compounds - VOCs) 

Data collected periodically on 70 VOCs, but limited number of measurements
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 

PROSPECTIVE STUDY

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.
TOTAL # OF STUDENT-DAYS 

ON WHICH

SYMPTOMS, MEDICATIONS, 

AND PEFR ENTERED = 4,777

TOTAL # OF STUDENT-DAYS 

DATA COLLECTED

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 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.
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
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
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 same day, 1- and 2-day lagged SO2 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)
Best Fit for Model

• PEAK 5-MINUTE 

DAYTIME (6AM-8PM) SO2 from Belvidere

• MEAN PRIOR DAY SO2 from Belvidere

• DAYTIME TEMPERATURE (7AM-6PM)
Same effect of SO2

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 

Model applied to White & Harmony 

using Belvidere HS SO2 Data

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
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
SO2 values in Belvidere: Ranged up to -

21 ppb for Daily Mean SO2

On 16 (11%) of 141 days, 

the daily mean SO2 was > 10 ppb

331 ppb for 5-minute Daytime Peak SO2

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...
Coefficient 

PValue

% 

Reduction 

in PEFR

5-minute 

Results of Final PROC Mixed Model 

With All 47 Subjects

Daytime (6am-8pm)

Maximum 

SO2 -0.06932 0.0071 -0.69%

For a 100 ppb 

increase in SO2

Prior Day 

Mean SO2 -1.1434 0.0004 -1.1%

For a 10 ppb 

increase in SO2
The total variability among the peak flow rates was 

not the same for all students; the study’s statistician 

examined the contribution of each of the 47 students 

to the model

Analyses were conducted to determine 

which subjects contributed particularly to 

the observed associations

to the model

The statistical association between SO2levels and 

peak flow rates appeared to vary with individuals

– 2 students appear highly sensitive to SO2

– 33 students appear to be somewhat sensitive to 

SO2

– 12 students appear not to be sensitive to SO2
Coefficient 

PValue

% 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

-5.8%

For a 10 ppb 

Post-hoc sub-group Multivariate analyses

SO2 Prior Day Mean -5.9878 <0.0001 -5.8%

For a 10 ppb 

increase in SO2

Somewhat 

Sensitive 

Subjects (n=33)

SO2 5-minute 

Daytime Max -0.07286 0.0326 -0.73%

For a 100 ppb 

increase in SO2

SO2 Prior Day Mean -8.7320 0.0404 -0.87%

For a 10 ppb 

increase in SO2
Student A – Bivariate Display of Data

Belvidere resident, grade 7, male

5-minute Daytime SO2 Max vs. ln of Peak Flow

Univariate Analysis

6.4

6.6

6.8

Prior Day SO2 Mean vs. ln of Peak Flow

Univariate Analysis

6.4

6.6

6.8

y = -0.1358x + 6.4426

R2 = 0.0067

at

SO2=0, ln(pf)=6.443

SO2=0.100ppm, ln(pf)=6.429

-1.4% in peak flow

5.6

5.8

6

6.2

6.4

0 0.1 0.2 0.3 0.4

SO2 5-min daytime max (ppm)

ln

of P

F

Subject A

Linear (Subject A)

y = -7.7717x + 6.4699

R2 = 0.165

at SO2=0, ln(pf)=6.470

at SO2=0.01ppm, ln(pf)=6.392

-7.5% in peak flow

5.6

5.8

6

6.2

6.4

0 0.005 0.01 0.015 0.02 0.025

Prior Day SO2 Mean (ppm)

ln

of P

F

Subject A

Linear (Subject A)
Student B – Bivariate Display of Data

White Twp resident, grade 5, male

5-minute Daytime SO2 Max vs. ln of Peak Flow

Univariate Analysis

5.7

5.8

5.9

6

Prior Day SO2 Mean vs. ln of Peak Flow

Univariate Analysis

5.7

5.8

5.9

6

y = -0.1866x + 5.8107

R2 = 0.0102

at SO2=0, ln(pf)=5.811

at SO2=0.100ppm, ln(pf)=5.792 

-1.9% in peak flow

5

5.1

5.2

5.3

5.4

5.5

5.6

5.7

0 0.1 0.2 0.3 0.4

SO2 5-Minute Daytime Max (ppm)

ln

of P

F

Subject B

Linear (Subject B)

y = -10.379x + 5.8396

R2 = 0.2174

at SO2=0, ln(pf)=5.840

at SO2=0.01ppm, ln(pf)=5.736 

-9.9% in peak flow

5

5.1

5.2

5.3

5.4

5.5

5.6

5.7

0 0.005 0.01 0.015 0.02 0.025

Prior Day SO2 Mean (ppm)

ln

of P

F

Subject B

Linear (Subject B)
Association between

Mean Prior-Day SO2 and PEFR

This model predicts overall for the 47 

students, that for a 10 parts per billion (ppb) 

increase increase in prior in prior-day mean SO there is an 2there 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.
This model predicts overall for the 47 

students, that for a 100 ppb increase in 

peak same-day SO there is an average 

Association between 

Max Same-Day SO2 & PEFR

peak same-day SO2there is an average 

decrement in PEFR of 0.69% 

For the 2 most Sensitive Students, this 

effect was nearly triple (-3.1%).
CURRENT FEDERAL GUIDELINES

SO2 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 ].

This corresponds to an average over the five minutes 

of 615 ppb.
CURRENT FEDERAL GUIDELINES

SO2 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.
SUMMARY

We observed significant effects on peak flow rate at 

levels well below the federal 24 hour standard (mean 

daily value) for SO2 of 140ppb, which had been set to 

deal with short term effects in the overall population.

Some asthmatics appear to be especially sensitive to 

SO2. Relatively low levels of SO2 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. 
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.
LIMITATIONS

• The statistical association does not rule out that 

the effect is due to an unmeasured factor that 

correlates with both SO2and peak flow.

• The study was conducted in a single region, and 

thus cannot be assumed to necessarily generalize 

to other communities.
RECOMMENDATIONS

Given that some persons may be 

especially sensitive to SO2, the definition 

of what constitutes a “safe level” may need 

to be revised. 

Some asthmatics may need to be 

especially cognizant of SO2 pollution in 

their region and may need to attempt to 

modify their exposure when levels are high.
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/

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.
Supplemental Slides
USE OF WEB-BASED 

QUESTIONNAIRE
POTENTIAL ADVANTAGES

PAPER VERSION

Administration of 

daily 

WEB BASED

Web based system 

daily accessed by 

questionnaires can 

be time and labor 

intensive, paper 

needs periodic 

retrieval

accessed by 

participate at his/her 

convenience, entry 

often faster, contact 

with staff minimized
PAPER VERSION

Compliance, 

particularly for 

children/adolescents, 

WEB BASED

Children/adolescents 

are on computers 

daily so smaller 

POTENTIAL ADVANTAGES

children/adolescents, 

is often low for daily

questionnaires

Compliance rate 

unknown until 

attempting to retrieve 

data

daily so smaller 

intrusion in their 

lives 

Compliance checked 

in real time
PAPER VERSION

Paper questionnaires 

require subsequent 

entry with associated 

WEB BASED

Data is directly added 

to data base, minimal 

errors

POTENTIAL ADVANTAGES

entry with associated 

transcription errors

errors

Checks can be made to 

restrict to valid entries

Data can be reviewed 

quickly so participants 

can be contacted for 

questions
SURVEY INSTRUMENT

Section 1 (28 questions)

Details on symptoms, triggers, location and peak 

flow rate

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
The home page contains a login, relevant links, important

announcements, and information. 

These are changed periodically.
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

MEDICAL USE SECTION

Comprehensive medication tracking 

includes time of intake and dosage

A user’s 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

CONCLUSIONS

Web Based Questionnaires are 

feasible for daily entry from 

adolescent and children (grades 4 –

12) – data from 64 students data from 64 students over 2 – 4 

months obtained

Real time monitoring can help 

improve compliance and quality

When combined with telephone/ 

e-mail reminders and incentives
CONCLUSIONS

(continued)

Data entry errors are greatly reduced

Entry can be more rapid than paper –

(only 5 – 10 minutes per day required) 10 minutes per day required)

Has potential for use in large 

epidemiological studies for population 

who typically access computer
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. 
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 subject’s responses were plotted 

chronologically to examine trends in the data 

and for individual data points that differed 

from the previous and next days data. 
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. 
Least Sensitive Subjects (n=12)

Coefficient P-value

SO2 5-minute Daytime 

Maximum 0.006307 NS

Post-hoc sub-group Multivariate analyses

Maximum 0.006307 NS

SO2 Prior Day Mean -0.00048 NS
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