United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
Research and Development
EPA-600/S1-81-033 June 1981
Project Summary
Effects of Participate
Air Pollution on
Asthmatic Subjects
Robert A. Kinsman, Hyman Chai, David W. Dickey, Richard Jones, Callis G.
Morrill, Ginger B. Perry, Sheldon L. Spector, and Philip C. Weiser
While much remains to be under-
stood, individuals with respiratory
disease appear to be affected by high
levels of air pollution as indicated by
subjective reports, clinic and hospital
visits, and morbidity. Suspended
particulates make up a substantial part
of urban air pollution, and specific
components of particulates, such as
sulfates and nitrates, when combined
with moisture, form acids with
properties potentially irritating to the
lung. The available research literature
has not clearly implicated the
components of suspended particu-
lates which do exert an immediate
effect upon the health status of
individuals with respiratory disease.
The present study focuses upon the
acute or short-term effects of sus-
pended particulates upon asthmatic
individuals. It has incorporated several
unique features. Extensive medical
characterization of each subject's
asthma was available, and individuals
with other respiratory or medical
conditions were not included. Recent
advances in methods of particulate
measurement, based upon dichoto-
mous sampling of particulates via
virtual impactor techniques, were
incorporated in the study. The daily
health status of the asthmatic subjects
was considered to be a concept that is
best defined by employing three
different types of measurements,
selected in order to triangulate on the
more immediate health effects of air
pollution upon the asthmatic subjects.
Of all the atmospheric pollutants
studied, only the fine IPM nitrate
fraction gave any indication of a rela-
tionship to the health status of
ashtmatic subjects.
This Project Summary was develop-
ed by EPA's Health Effects Research
Laboratory, Research Triangle Park,
NC, to announce key findings of the
research project that is fully docu-
mented in a separate report of the
same title (see Project Report ordering
information at back).
Introduction
The time period of the study consider-
ed here is from January through March
1 979, when the pollutants to be meas-
ured were at their highest and most
fluctuating levels in Denver, where the
study took place.
Screening of the subjects prior to
study included: confirmation of peren-
nial asthma symptoms, methacholine
inhalation challenge, twice-daily peak
expiratory flow rate during a 5- to 7-day
period, medical history, physical
examination, prick tests, chest x-ray,
electrocardiogram, and use of the
Panic-Fear Personality Scale to identify
and exclude patients with excessively
high characterological anxiety known to
be associated with medication overuse
and arbitrary use.
Of 41 well-characterized asthmatic
subjects selected for the study, 24 met
the criterion of 60% complete data
within the target period January 1979
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through March 1979, after the elimina-
tion of daily measurement periods when
upper respiratory infections were
reported and periods when subjects
were out of the Denver metropolitan
area for more than three hours during a
12-hour measurement period. All
subsequent analyses focused upon
these 24 subjects, 9 males and 15
females. All lived within 2.5 miles of one
of two air quality monitoring stations.
All were taking a theophylline
preparation or an oral beta agonist on a
regular schedule as a basic
bronchodilator, while 8 subjects also
supplemented this medication regimen
with daily or alternate-day oral cortico-
steroids. In addition, all subjects tookan
aerosolized bronchodilator on a discre-
tionary, as-needed basis to relieve
episodes of acute breathing difficulty.
Study Parameters
Exposure measurements recorded at
the two monitoring stations included:
fine fractions (< 2.5 /urn) and coarse
fractions (between 2.5//mand 15jum)of
inhaled particulate matter (IPM), includ-
ing mass, nitrates, and sulfates, sulfur
dioxide, carbon monoxide, ozone,
ambient temperature, and barometric
pressure. Subject responses to expo-
sure were evaluated by obtaining twice
daily measurements of three health
status variables: peak expiratory flow
rate (PEFR) measured by Mini-Wright
Peak Flow Meter, usage of as-needed
aerosolized bronchodilators recorded by
nebulizer chronolog with concurrent
manual recording of time and amount
for each use, and subject rating of nine
discrete symptoms of breathing diffi-
culty
The objectives of the statistical
analyses were to test the study's null
hypotheses pertaining to the effects of
air pollution upon each of the three
health status measurements, namely
that:
• Elevated pollution levels do not
significantly increase'the severity
of reported airways obstruction
symptoms,
• Elevated pollution levels do not
significantly decrease peak expir-
atory flow rates, and
• Elevated pollution levels do not
significantly increase the usage of
as-needed aerosolized broncho-
dilators.
These hypotheses were tested by
LEAPS AND BOUNDS Multiple Linear
Regression Analyses (including corre-
lation analyses, multiple linear regres-
sion analyses for individuals, and
aggregate multiple linear regression
analyses for groups) and by the applica-
tion of a random effects model.
Results
For both air quality monitoring
stations, average values for fine and
coarse IPM were high and variable dur-
ing the months of January and February
compared with March levels. In general,
the East Denver station had notably
higher 7 AM fine IPM mass levels than
the West Denver station, a difference
that was particularly noticeable in
January and February. For the IPM com-
ponents, fine and coarse IPM sulfates
and fine IPM nitrates were also general-
ly higher for the 7 AM collection period,
and higher at the East than the West
Denver station. For these variables, a
continuous decrease in monthly mean
levels was discernible from January
through March. Average coarse IPM
nitrate levels were generally low
throughout the study period and at both
stations. Mean carbon monoxide and
sulfur dioxide levels reflected certain
tendencies similar to those of the IPM
variables, showing higher levels at the
East Denver station. These levels gener-
ally were decreasing from January
through March. By contrast, mean
levels of ozone, while consistently low,
show a definite increase across months.
Morning temperatures rose from an
average of -9°C to +1 °C, while average
evening temperatures increased from
-7°C to +5°C during the same period.
Monthly average morning and evening
barometric pressures were consistently
at approximately 29.9 in. Hg across the
three months.
A correlation matrix for the environ-
mental and meteorologic variables for
both stations during the 71 days avail-
able for the three-month period studied
shows that fine and coarse IPM mass
shared approximately 25% common
variance. Fine IPM mass was also
moderately related to the gaseous air
quality variables (inversely to ozone)
and to fine IPM sulfate and nitrate levels
at both stations. The relationships of
coarse IPM mass to fine and coarse IPM
sulfates and nitrates were consistently
low. Fine IPM mass values were always
correlated with temperature, coarse
IPM mass levels were nearly indepen-
dent of temperature.
While certain moderate relationships
exist among the health status measure-
ments, there is actually notable varia-
tion in the magnitude of the relation-
ships. The average relationships
between nebulizer usage and the
objective measurements of airways
obstruction were always negative and
quite low. Nebulizer usage was some-
what more reliably related to subjective
ratings of airways obstruction than to
PEFR, indicating a tendency for subjects
to use their nebulizers more frequently
when they reported more airways
obstruction.
Univanate correlational analyses
showed an inconsistency in the pattern
of correlations among the health status
measurements across both stations.
This inconsistency obtained for each of
the environmental and meteorologic
variables, although Fisher's tests indi-
cated that a significant relationship
obtained among the associated p-
values for the correlations for coarse
IPM sulfates and fine IPM nitrates. On
the basis of these preliminary analyses,
both fractions of IPM sulfates and
nitrates were retained for the subse-
quent multiple linear regression
analyses, while gaseous air quality, '
meteorologic, and fine and coarse IPM
mass variables were all excluded.
LEAPS AND BOUNDS multiple linear
regression analyses by individual sub-
jects included no predictor variables
that improved upon no regression or the
best univariate regression. This was
true for each health status measure-
ment. Most notably, IPM measurements
of fine and coarse sulfates and nitrates
rarely predicted the health status of
individual subjects and generally were
inconsistent in direction among individ-
uals when they appeared at all. In the
aggregate LEAPS AND BOUNDS
multiple linear regression analyses, the
12 subjects assigned to each station
were considered as a group. For each of
the three health status measurements
there are four aggregate regressions
defined by two stations and two time
periods. In all cases, the model con-
formed to the analyses for individuals,
using the previous health status
measurement, and fine and coarse IPM
sulfates and nitrates as the predictor
variables. Only two of the IPM compon-
ents appeared as best predictors ir
these analyses. Coarse IPM sulfates
were positively associated with PEFF
for the 7 AM period and negatively
associated with nebulizer usage for the
7 PM period at the West Denver station
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The paradoxical nature of these rela-
tionships and the failure of coarse IPM
sulfates to appear within the regres-
sions at the East Denver station or at the
other time period suggest that the
relationships are due to chance. Fine
IPM nitrates appeared as a best predic-
tor three times, negatively for 7 AM
PEFR, positively for 7 PM nebulizer
usage at the West station, and positively
for the? PM subjective report of airways
obstruction at the East station. Results
of application of the Random Effects
Model support the LEAPS AND
BOUNDS multiple linear regression
analyses, suggesting that fine IPM
nitrates may have influenced nebulizer
usage and symptom reports, while no
other air pollutant adversely affected
health status.
Robert A. Kinsman, Hyman Chai, David W. Dickey, Richard Jones, Callis G.
Morrill, Ginger B. Perry, Sheldon L. Spector, and Philip C. Weiser are with the
National Jewish Hospital/National Asthma Center, Denver, CO.
Dorothy Calafiore is the EPA Project Officer (see below).
The complete report, entitled "Effects of Paniculate Air Pollution on Asthmatic
Subjects," (Order No. PB 81-190 514; Cost: $9.50, subject to change) will be
available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Conclusion
Of all the atmospheric pollutants
studied, only the fine IPM nitrate
fraction gave any indication of a rela-
tionship to the health status of the
asthmatic subjects. In the final series of
analyses, increased fine IPM nitrates
tended to be associated with increased
subjective reports of airways obstruc-
tion and increased aerosolized broncho-
dilator usage when all subjects were
combined. Because of the number of
comparisons made, these results, while
in the expected direction indicative of an
effect, may well be attributed to chance.
We did, however, select a conservative
approach to help guard against chance
results by using two-tailed statistical
tests for clearly directional a priori
hypotheses. Neither any other fraction
of IPM, any gaseous air quality variable,
nor any meteorologic measurement
produced any consistent effect on the
health status of asthmatic subjects. The
determination of any threshold at which
a change in health status occurs is thus
precluded by the nature of these results.
* US GOVERNMENT PRINTING OFFICE 1981-757-012/7139
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