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

-------
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

-------
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

-------
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Postage and
Fees Paid
Environmental
Protection
Agency
EPA 335
Official Business
Penalty for Private Use $300
       PS   0000329
       U  S  ENVIR  PROTECTION  AGENCi
       REGION  5 LIBRARY
       230  & DEARBORN STREET
       CHICAGO  IL  60604

-------