|
Carbon Monoxide
CARDIAC RESPONSE TO MONOXIDE IN THE NATURAL
ENVIRONMENT. Principal Investigator: Steven D.Colome, Sc.D. University of California, Irvine. 1992. A3-138-33.
EFFECTS
OF EXPOSURE TO LOW-LEVEL CARBON MONOXIDE AT SEA LEVEL AND HIGH ALTITUDE IN SENSITIVE SUBJECTS. University of California,
Irvine. 1991. A833-159, A6-203-33, and A3-138-33.
Objectives: To determine whether
the current high-altitude standard for carbon monoxide is justified in view of the fact that the parameters used
in the model calculations for deriving the standard were flawed. To validate with state-of-the-science techniques
some of the variables used in calculating the sea level CO standard. Three studies were funded to address specific
issues involved in order to draw definitive conclusions.
Findings: In patients suffering
from ischemic heart disease, carbon monoxide exposure reduced the time before onset of angina to a greater degree
at a simulated altitude of 7,000 feet than at sea level.
Importance to ARB's Program: The
results indicated the need for a separate high altitude carbon monoxide standard for the State and reconfirmed
the existing sea level standard during the recent review of the standard by ARB.
A COORDINATED MULTIDISCIPLINARY RESEARCH
PROGRAM ON CARBON MONOXIDE HEALTH EFFECTS. Principal Investigator: Michael T. Kleinman, Ph.D. University of California,
Irvine. 1990. A6-203-33.
AN EPIDEMIOLOGICAL SURVEY OF CARBOXYHEMOGLOBIN
IN NONSMOKERS IN LOS ANGELES. Department of Public Health, Berkeley. 1975.
ARB-847
INFLUENCE OF CARBON MONOXIDE ON CARDIAC DYNAMICS IN NORMAL
AND CARDIOVASCULAR STRESSED ANIMALS. Principal Investigator: Steven M. Horvath, Ph.D. University of California,
Santa Barbara. 1974. ARB-2096.
Children's Health
EPIDEMIOLOGIC INVESTIGATION TO IDENTIFY HEALTH EFFECTS OF
AMBIENT AIR POLLUTANTS IN CALIFORNIA. Principal Investigator: John M. Peters, M.D., Sc.D. University of Southern
California. 2004. 94-331.
Objectives: The objectives
of this study are to: 1) determine whether long-term exposure to ambient air pollutants during childhood leads
to changes in lung function or adverse health effects, especially chronic respiratory effects; and 2) quantify
the prevalence and severity of the observed effects, as well as the levels of exposure at which effects occur.
The study will evaluate 5,400 school children residing in 12 southern California communities, 3,600 of which have
already been studied for two years as part of a similar study begun in 1991.
Importance to the ARB:
The ambient air quality standards set by the ARB are determined, in
part, by the reactivity of the population most sensitive to a
particular pollutant (e.g., children, cardiac patients,
asthmatics). However, most of the health studies used to set both
State and federal standards have focused on short-term effects; little
has been done to determine the cumulative effects of long-term
exposure, especially for children growing up in smoggy
environments. The results from this study will be used to
validate and update existing exposure models and evaluate the
effectiveness of current ambient air quality standards.
DETERMINATION OF THE ELEMENTAL CARBON AND ORGANIC CARBON
CONCENTRATIONS DURING THE SOUTHERN CALIFORNIA CHILDREN’S HEALTH STUDY , 1999-2001. Principal Investigator:
Lynn G. Salmon California Institute of Technology, Pasadena. 2004. 01-309.
INTERIM REPORT FOR THE FRESNO ASTHMATIC
CHILDREN'S ENVIRONMENT STUDY (FACES). University of California, Bekerley. 2002.
99-322 & 99-323
DETERMINATION OF THE ELEMENTAL CARBON, ORGANIC COMPOUNDS,
AND SOURCE CONTRIBUTIONS TO ATMOSPHERIC PARTICLES DURING THE SOUTHERN CALIFORNIA CHILDREN’S HEALTH STUDY.
Principal Investigator: Lynn G. Salmon California Institute of Technology.
2000. 98-320.
Objectives: The objectives of this
project are to: 1) analyze all archived quartz fiber filters from the Children’s Health Study, from 1994
and 1996-98, for their organic and elemental carbon content; 2) analyze the 1995 quartz fiber filters for individual
organic compounds that act as tracers for source emissions; and 3) use the resulting organic compound concentration
data to model the source apportionment of the organic aerosol and aerosol mass measured during 1995.
Importance to ARB’s Program: The
attention of health investigators has recently been focused on the impacts of combustion-derived particles on human
health. By determining the concentration of organic carbon compounds and elemental carbon particles in southern
California from 1995-1998, this project will provide an important piece of the information needed to complete the
PM2.5 database for the Children’s Health Study (Contract No. 94-331).
EPIDEMIOLOGIC INVESTIGATION TO IDENTIFY
CHRONIC HEALTH EFFECTS OF AMBIENT AIR POLLUTANTS IN SOUTHERN CALIFORNIA (Three-phase project). Principal Investigator:
John M. Peters, M.D. University of Southern California. 1996. A033-186.
Objectives: The objectives of the
project in its entirety are: 1) to determine whether long-term exposure to southern California's unique mixtures
and concentrations of ambient air pollutants during childhood development leads to changes in lung function or
identifiable adverse health effects, especially chronic respiratory effects; and 2) to quantify the prevalence
and severity of the observed health effects and the levels of exposure to specific pollutants at which the effects
occur.
The primary specific objective of Phase I was to produce a cost-effective research
plan for Phases II and III that offered the greatest likelihood of success in meeting the overall project objectives,
and to develop a final detailed protocol for Phase II.
The specific objectives of Phase II are to verify community exposure classifications,
collect data to be used in personal exposure models, gather baseline health and lifestyle data for the children
under study, perform cross-sectional analyses to determine community differences that are a function of air pollution,
and finalize the Phase III protocol, based on Phase II findings.
Findings: Phase I: 1) Based on
potential long term exposure health effects, and on high ambient concentrations, the project should focus on ozone,
particulate pollution, nitrogen dioxide, and acidic pollutants (nitric, hydrochloric, and organic acids); 2) to
achieve statistically meaningful results, twelve communities with different ratios of these pollutants should be
included in the study; 3) during Phase II, the project should study between-community differences in the health
of school children from the fourth, seventh, and tenth grades, and then follow these children's health status through
their high school graduation (year 2 of Phase II, and Phase III); and 4) a state-of-the-science exposure assessment
program should be implemented to help separate out the effects of one pollutant from another. Phase II: This phase
of the study was recently completed. ARB staff are in the process of reviewing the data for completeness and accuracy.
Importance to ARB's Program: Information
obtained from this project, which is the cornerstone of the ARB's Long-Term Exposure Health Effects Research Program,
will allow, for the first time, quantitative consideration of long-term exposure effects of ambient criteria air
pollutants. The information will have direct application in the review and, if necessary, revision of California's
health-based ambient air quality standards. The project will also provide information necessary to determine the
need for an ambient air quality standard for atmospheric acidity.
DEVELOPMENT OF A PROTOCOL TO TRACE AND
STUDY SCHOOL CHILDREN EXPOSED TO VINYL CHLORIDE. Principal Investigator: Richard Ziskind, Ph. D. Science Applications,
Inc. 1984. A1-082-32.
HEALTH EFFECTS IN CHILDREN EXPOSED TO VINYL
CHLORIDE. Principal Investigator: Richard A. Ziskind, Ph. D. Science Applications, Inc. 1981. 68-2986.
Clinical Studies
ARE MUCIN AND MUCIN RNA RELIABLE MARKERS FOR HYPERSECRETION
IN HUMANS WITH IRRITANT-INDUCED BRONCHITIS? Principal Investigator: Carol Basbaum, Ph.D. University of California,
Irvine. 1992. A933-095.
Objectives: To develop and evaluate
two new test methods for early detection of increased mucus production in the respiratory tract of humans. One
measures an increase in the levels of mucin in airway lining fluid; the other identifies a signal inside the cells
that indicates increased mucus production. Increased mucus production is one of the first signs of chronic bronchitis.
Findings: The study was successful
in developing and validating the new test methods and in assuring a high degree of sensitivity in detecting changes
in mucus production.
Importance to ARB's Program: The
tests have been included for further evaluation in other pollutant exposure studies.
AIR POLLUTION EFFECTS ON NASAL FUNCTION. Principal Investigator:
Homer A. Boushey, M. D. University of California, San Francisco. 1988. A5-163-33.
EFFECTS OF AIR POLLUTION ON AIRWAY FUNCTION. Principal Investigator: J. A. Nadel. 1982. A9-115-30.
DEVELOPMENT AND APPLICATION OF METHODS
FOR ESTIMATING INHALABLE AND FINE PARTICLE CONCENTRATIONS FROM ROUTINE HI - VOL DATA. Principal Investigator: John
Trijonis and Marilyn Davis. Santa FE Research Corporation. 1981.
A0-076-32.
RESPONSE OF INDIVIDUALS WITH REACTIVE AIRWAY DISEASE
TO ATMOSPHERIC POLLUTANTS INCLUDING SULFATES. Principal Investigator: Roger Detels, M. D. UCLA School of Public
Health. 1980. A6-216-30.
PHYSIOLOGICAL EFFECTS OF AIR POLLUTANTS
IN HUMANS SUBJECTED TO SECONDARY STRESS. Principal Investigator: Jack D. Hackney, M. D. Rancho Los Amigos Hospital
Inc. 1974. ARB-2-372.
PHYSIOLOGICAL EFFECTS OF AIR POLLUTANTS DURING LONG AND
SHORT TERM WORK IN 25°C AND 35°C TEMPERATURE. Principal Investigator: Peter B. Raven, Ph.D. University
of California, Santa Barbara. 1974.
ARB-2098.
Fuels
STUDY OF NEUROLOGICAL EFFECTS OF LOW-LEVEL METHANOL EXPOSURE
IN NORMAL AND FOLATE-DEFICIENT SUBJECTS. University of California, San Francisco.
1994. A033-172.
Objectives: To determine the neurological
effects of exposure to methanol vapor using normal and folate-deficient human volunteers. Because methanol is used
as an alternative fuel for motor vehicles, research is needed to determine whether exposure to the vapors is harmful
at the threshold limit value (TLV). TLVs are the maximum allowable concentrations at a work site. Folate-deficient
subjects need to be tested as a sensitive subgroup because folate tends to inhibit the formation of formate, a
toxic metabolite of methanol.
Findings: In normal individuals,
exposure to TLV levels of methanol causes a transient increase in blood methanol levels but no change in formate
levels or in neurological test results. Evaluation of the folate-deficient subjects is currently in progress.
Importance to ARB's Program: The
findings from this project will be used to estimate the health risk posed by methanol vapors during motor vehicle
refueling activities.
DERMAL ABSORPTION OF METHANOL AND METHANOL/GASOLINE MIXTURES.
Principal Investigator: O.G. Raabe, Ph.D. University of California, Davis.
1992. A933-186.
Objectives: To determine whether
the skin absorption of methanol is increased in methanol/gasoline mixtures. Because methanol is used as an alternative
fuel for motor vehicles, research is needed to determine whether skin absorption of methanol from accidental spills
is enhanced by the presence of gasoline in methanol/gasoline mixtures.
Findings: Methanol/gasoline mixtures
with greater than 50 percent gasoline increased the relative degree to which methanol was absorbed by rat skin.
The total amount of methanol absorbed from the mixtures, however, was less than that from pure methanol fuel because
of the lower content of methanol in the mixtures.
Importance to ARB's Program: These
findings helped ARB conclude that accidental spills of methanol/gasoline mixtures that occur in gas stations are
not likely to pose a risk to humans.
General
THE EFFECT OF SMOKE FROM THE BURNING OF RICE STRAW AND OTHER
VEGETABLE MATTER RESIDUE ON AIRWAY INFLAMMATION AND PULMONARY FUNCTION IN HEALTHY, ASTHMATIC AND ALLERGIC INDIVIDUALS.
Principal Investigator: Colin Solomon, Ph.D. University of California, San Francisco. 2003. 97-322.
Objective: The objective
of this project is to investigate the effects on human respiratory health of particles inhaled from common sources
of smoke produced by burning of vegetable matter, specifically by determining the effects of: 1) an acute
exposure at two different concentrations to rice straw smoke on airway inflammation and pulmonary function; 2)
total smoke exposure (single vs. multi-day) on airway inflammation and pulmonary function; and 3) asthma and allergy
status on airway inflammation and pulmonary function responses to smoke from rice straw burning.
Importance to ARB’s Program: Past
epidemiology studies have provided consistent and coherent data linking observed health effects and PM exposure.
However, PM10 is a complex air pollutant made up of many different kinds and sizes of particulates. It is
very likely that different kinds of particles, of varying sizes, from different sources of particulate air pollution,
act by a variety of biological mechanisms to cause the various health effects seen with PM10 exposure. One
source of PM exposure of particular concern in California’s central valley is smoke from the burning of vegetative
matter, including rice straw residues. The results from this study will provide valuable information necessary
to adequately evaluate the existence, nature, and extent of adverse health effects associated with exposure to
this source of particulate air pollution in California. The results of this project may also assist the ARB in
determining whether additional actions, if any, are needed to address burning of agricultural and forest wastes.
CHRONIC TOXICITY OF MIXED AIR POLLUTANTS: OXIDANTS, ACIDS,
AND FINE PARTICLES. Principal Investigator: William. J. Mautz, Ph.D. University of California, Irvine. 1993. A833-104.
Objectives: To determine the adverse
effects resulting from long term (9 months) episodic exposures to low levels of ozone both alone and in combination
with other pollutants, simulating ambient conditions in Los Angeles.
Findings: The effects included
lung structural changes and a breakdown in lung defense mechanisms. The magnitude of adverse effects was greater
in the ozone group than in the clean air group, but was statistically significant only in the group exposed to
ozone with other pollutants. Although the acute effects of air pollution appear to be mainly caused by oxidants,
the chronic effects may be influenced to a large extent by the presence of particulate material and ambient acids.
Importance to ARB's Program: These
findings will be useful in evaluating the chronic effects of air pollution and in estimating the risk from air
pollution for various districts.
A PILOT SURVEY OF HUMAN LUNG TISSUE FOR AIR POLLUTION
EFFECTS IN LOS ANGELES COUNTY. University of Southern California. 1990. A6-202-33.
Objectives: To test the feasibility
of collecting pathological specimens for analysis of lung tissue for air pollution effects from victims of traffic
accidents and homicides and correlating this information with demographic, health, and lifestyle data. This study
was a part of ARB efforts to determine chronic and lifetime effects of exposure to ambient air pollution.
Findings: The method was demonstrated
to be feasible if it includes individuals younger than 15 years. Presence of lung lesions at a young age was higher
than expected. ARB staff recommend further studies to determine whether these findings are linked to air pollution.
Importance to ARB's Program: Most
existing air quality standards are aimed at protecting the public against acute effects. Information on chronic
effects is critical for future review of the standards.
EFFECT OF POLLUTANT EXPOSURE AMBIENT AIR
IN CHILDHOOD AND ADULTHOOD. Principal Investigator: David H. Wegman, Ph.D. University of California, LA. 1987. A4-068-33.
21-DAY EXPOSURE TO MIXED AIR POLLUTANTS:
EFFECTS ON LUNG AIRWAYS AND MACROPHAGES. Principal Investigator: Robert F. Phalen, Ph. D. University of California,
Irvine. 1987.
A6-126-33.
INDUCTION OF ARYL HYDROCARBON HYDROXYLASE
IN CULTURED PERIPHERAL LYMPHOCYTES IN COLLEGE STUDENTS EXPOSED TO AIR POLLUTANTS. Principal Investigator: Robert
W. Teel, Ph.D. University of Loma Linda , CA. 1978. A6-104-30.
HEALTH EFFECTS OF ATMOSPHERIC SALTS AND GASES
OF SULFUR AND NITROGEN IN ASSOCIATION WITH PHOTOCHEMICAL OXIDANT. Principal Investigator: T. Timothy Crocker, M.
D. University of California,
Irvine. 1972.
3-197
Volume I
Volume II
Nitrogen Oxides
EFFECTS OF NITROGEN DIOXIDE ON AIRWAY INFLAMMATION
IN ALLERGIC ASTHMATIC SUBJECTS. Principal Investigator: Colin Solomon, Ph.D. University of California, San Francisco.
2004.
00-337.
THE HEALTH IMPACT OF NITRIC OXIDE: EFFECTS ON LUNG
FUNCTION AND CELLULAR AND BIOCHEMICAL PROCESSES IN HEALTHY HUMANS. University of California, San Francisco.
Principal Investigator: Stephen C. Lazarus, M.D. University of
California, San Francisco. 2001. 97-329.
Objectives: The objectives of this
project are to: 1) review the basic scientific, clinical, and epidemiologic literature relating to nitric oxide
(NO); 2) assess the effects of ambient levels of NO on humans; and 3) evaluate the potential for ambient nitric
oxide to cause or worsen human disease.
Importance to ARB’s Program: There
is reason to suspect that chronic exposure to even low levels of ambient NO may have significant effects in the
body. This concern is supported by epidemiologic studies that indicate an association between ambient concentrations
of nitric oxide and the incidence of adverse health effects in humans, including respiratory infections, croup,
asthma, and bronchitis. It is expected that a comprehensive literature review will provide the ARB with sufficient
information to determine the potential for ambient concentrations of NO to cause or modify human disease.
It will also allow the ARB to determine whether enough data exist to address the concerns regarding ambient NO
exposure and possible adverse human health effects or, if not, what additional studies are needed.
THE EFFECTS OF MULTI-DAY EXPOSURE TO NITROGEN DIOXIDE ON
CELLULAR IMMUNITY: HUMAN MACROPHAGE RESPONSES. Principal Investigator: Michael T. Kleinman. University of California,
Irvine. 1998. 95-311.
Objectives: To determine whether
repeated short-term exposure to nitrogen dioxide (NO2) causes changes in macrophage function such as phagocytic activity and the ability to release
inflammatory substances, and to determine whether NO2 exposure causes macrophage overactivation, which could lead to increased cellular damage.
Findings: The results indicate
that NO2 exposure does not affect
the body's production of macrophages, and that NO2 exposure does not affect the potential ability of macrophage cells to recognize and ingest invading
pathogens such as bacteria or viruses. Nor did NO2 exposure appear to alter the ability of macrophage cells to recruit other infection-fighting cells.
However, following NO2 exposure,
macrophages were found to become "overexcitable" and release more potentially toxic inflammatory chemicals
than normal. This could cause tissue damage in the lungs of humans exposed to NO2 in the ambient environment.
Importance to ARB's Program: Because
oxides of nitrogen are common ambient air pollutants, and because epidemiologic evidence suggests that exposure
to ambient NO2 is associated with
increased incidence of respiratory symptoms, infection, and illness in humans and depressed immune system function
in animals, the ARB needs to determine the actual effects of NO2 on humans so that this knowledge can be used in considering air pollution standards.
THE EFFECTS OF MULTI-DAY EXPOSURE TO NITROGEN DIOXIDE ON
HUMAN CELLULAR IMMUNITY. Principal Investigator: John R. Balmes. University of California San Francisco. 1997.
93-317.
Objectives: To determine whether
extended exposures to nitrogen dioxide (NO2 ) at the current California one-hour ambient air quality standard level (0.25 ppm) can compromise
the human immune system. Recent evidence suggests that low-level NO2 exposures may weaken the immune system, compromising resistance to infections.
Findings: The results of this study,
when viewed with other clinical and epidemiological investigations, do not resolve the uncertainties of NO2 health and immune system impacts. It appears that
NO2 can impact the cellular processes
of the lung by its simple oxidative damage potential as is found with ozone exposure. These oxidative injuries
are reflected by the neutrophil cell increases reported in this study. Further, other studies find that NO 2 appears to produce complex alterations in immune
system function or function of individual cellular components of the immune system. However, the timeframes of
this and other past clinical exposure studies were short, and little change has been found, even -- in this study
-- following exposure to relatively high levels of NO 2. The investigators suggest that more prolonged exposures may impact immune system function.
Such studies area very difficult to perform on human volunteers exposed in experimental chambers.
Importance to ARB's Program: The
study provides the information required by the ARB to establish whether extended exposures to NO2 at the current standard level poses a threat to
public health. It does not support the findings of other studies in which NOx was observed to cause changes in the immune system.
CORRELATIVE AND SENSITIVE DISCRIMANTS FOR AIR QUALITY
CONTROL. Principal Investigator: Russell P. Sherwin, M.D. USC School Of Medicine Los Angeles, CA. 1989. A3-083-33.
EFFECTS OF AMBIENT AIR POLLUTION ON THE
LUNG AND IMMUNE SYSTEM. Principal Investigator: Russell P. Sherwin, M. D. University of Southern California. 1989. A4-160-33.
EFFECTS OF NITROGEN DIOXIDE ON AIRWAY CALIBER
AND REACTIVITY IN ASTHMATIC SUBJECTS; EFFECTS OF NITROGEN DIOXIDE ON LUNG LYMPHOCYTES AND MACROPHAGE PRODUCTS IN
HEALTHY SUBJECTS; NASAL AND BRONCHIAL EFFECTS OF SULFUR DIOXIDE IN ASTHMATIC SUBJECTS. Principal Investigator:
Homer A. Boushey, Jr., M. D. University of California, San Francisco. 1988. A6-200-33.
NITROGEN DIOXIDE EFFECTS ON PROGRESSION
OF MOUSE LYMPHOMA, A BLOOD CELL MALIGNANCY. Principal Investigator: Arnis Richters, Ph.D. School of Medicine Los
Angeles, CA. 1988. A5-162-33.
THE ROLE OF AIR POLLUTANTS IN FACILITATION
OF CANCER CELL METASTASIS. Principal Investigator: Arnis Richters, Ph.D. School of Medicine Los Angeles, CA. 1984. A2-128-33.
NEW APPROACH FOR DETECTION HEALTH HAZARDS
OF NO2 INHALATION. Principal Investigator: Arnis Richters, Ph.D. School of Medicine Los Angeles,
CA. 1983. A0-106-32.
IN VIVO FATE OF NITROGENOUS AIR POLLUTANT DERIVATIVES.
Principal Investigator: Norris J. Parks. University of California, Davis. 1982. A0-031-31.
NEW APPROACH FOR DETECTING HEALTH HAZARDS
OF NO2 INHALATION. Principal Investigator: Arnis Richters, Ph.D. School of Medicine Los Angeles, CA. 1981. A9-076-31.
IN VIVO FATE OF NITROGENOUS AIR POLLUTANT DERIVATIVES.
Principal Investigator: N. J. Parks. University of California, Davis. 1979. A7-190-30.
FATE AND DISTRIBUTION OF INHALED NITROGEN
DIOXIDE IN THE NON - HUMAN PRIMATE. Principal Investigator: Elliot Goldstein, M. D.University of California, Davis.
1974.
ARB-1116.
THE FATE OF NITRIC OXIDE IN THE MAMMALIAN
SYSTEM USING N15
AS TRACER AND ISOTOPIC DILUENT. Principal Investigator: Gustave Freeman,
M. D. and Michael Anbar, Ph.D. Stanford Research Institute. 1973. ARB-2-291.
Ozone
EFFECTS OF CONTROLLED OZONE EXPOSURE IN VOLUNTEERS
WITH CARDIOVASCULAR DISEASE. Principal Investigator: Henry Gong, Jr., M.D. Environmental Health Services. May 2000. 93-327.
Objectives: To conduct a pilot
study to determine whether acute exposure to ozone can adversely affect people suffering from ischemic heart disease
or hypertension.
Findings: The investigators were
unable to locate, enroll, and study an adequate number of patients with ischemia, so the study was performed on
patients with hypertension. While the study reports no clinically manifested adverse consequences of brief ozone
exposure to hypertensives, even though this group is considered to be at risk, it does suggest a physiologic basis
for concern for those with existing cardiovascular disease. Further experimental work of this type will be required
to resolve the issue.
Importance to ARB's Program: In
recent years epidemiological studies have reported a consistent correlation between urban air pollution levels
and an increase in mortality. In addition, it appears that people suffering from cardiac and/or pulmonary disease
are more prone than others to die from effects of air pollution. However, prior to this study, controlled laboratory
studies had not reported any biological response(s) that could explain the mortality effect resulting from ambient
pollutant exposures. This study provides evidence of biological response(s) to ozone that suggest that ozone exposure
added stress to the hearts of people studied. The evidence from this study suggests one mechanism whereby ozone
could impact the well-being of people with existing heart problems. The results provide further justification for
modification of existing public health advisories to explicitly protect people with heart disease.
EFFECTS OF OZONE ON PROTEASES AND PROTEASE INHIBITORS
OF THE HUMAN AND RAT LUNG. Principal Investigator: William B. Mautz, Ph.D.
University of California, Irvine. 2000. A033-175.
Objectives: To perform a detailed
analysis of the biochemical events (changes in proteases and protease inhibitors) that are believed to precede
connective tissue fibrosis (scarring) in lungs following exposure to air pollutants. In this study levels were
measured of connective tissue proteases and protease inhibitors in lung lavage fluid collected from rats and humans
following acute and/or chronic exposures to ozone alone or in combination with nitric acid.
Findings: No changes in protease
levels were found in rats or humans for any of the exposure conditions. The investigators did find that, in both
humans and rats, relatively low-level acute (but not subacute or chronic) ozone exposures resulted in striking
increases in the protease-inhibiting capacity of lung lavage fluid. These increases in protease-inhibiting capacity
were due to extensive cellular membrane damage and the release of intracellular contents and do not imply that
acute ozone exposure offers a protective effect by "increasing" the amount of inhibitory species in lung
fluids. Indeed, over time, because of the potential for permanent tissue damage, exposure to ozone could lead to
an overall reduction in the production of protective inhibitory species. The study confirms that acute ozone exposure
does cause tissue damage; however, it is unclear whether the mechanism leading to pulmonary fibrosis is tied to
changes in protease levels or to the possible reduction over time of protease inhibitory species due to direct
tissue damage.
Importance to ARB's Program: California's
current ambient ozone standard is based on a number of factors that include short-term changes in lung function.
The results of this study will contribute to the determination of whether the standards adequately protect the
public against the long-term effects of ozone exposure.
PULMONARY MACROPHAGE RELEASE OF INFLAMMATORY CYTOKINES AFTER
MULTI-DAY NITRIC ACID VAPOR AND OZONE EXPOSURE. Principal Investigator: Paul Blanc, MD, MSPH. University of California, San Francisco. 2000. 93-331.
Objectives: The magnitude of breathing
capacity declines following acute single exposure to ozone progressively diminishes with successive days of ozone
exposure. The objective of this study was to include additional health effects evaluation parameters (levels of
cytokines) for ARB-funded clinical studies in progress that are evaluating the multi-day exposure effects of ozone
and nitric acid. (Cytokines are biochemical mediators that are indicators of lung injury and are also responsible
for inflammatory changes in the lung.)
Findings: The utility of this work
awaits the completion of the core clinical study. Specific observations made in this study include: (1) Two of
the measured cytokines produced a clear indication of pollution-related response; (2) responses to ozone were found
to be similar in 1-day and 4-day exposure protocols; (3) nitric acid was found to stimulate production of the two
cytokines by itself but cytokine levels were reduced when nitric acid and ozone were administered together. The
findings of this study should prove useful in the interpretation of the results of the core clinical exposure study
-- they provide a mechanistic link among pollutant exposure, observed lung function changes, and injury observations.
Importance to ARB's Program: Adding
cytokine measurements to the ongoing studies will permit better evaluation of multi-day exposure effects of ozone
and/or nitric acid.
RELATIONSHIP BETWEEN ACUTE OZONE RESPONSIVENESS AND THE
CHRONIC LOSS OF LUNG FUNCTION IN RESIDENTS EXPOSED TO RECURRENT OXIDANT AIR POLLUTION. Principal Investigator:
Henry Gong, Jr., M.D. University of California, Los Angeles. 1998. A6-158-33.
Objectives: In the early l970s
a long-term study of chronic obstructive respiratory disease was initiated in Los Angeles County to monitor lung
function responses in residents of three air-polluted areas and one less-polluted site. By the mid-1980s, it was
found that subjects living in the polluted areas exhibited more rapid lung function declines than those living
at the less-polluted site. This study was conducted to retest a subset of the participants of the earlier study
to determine what, if any, changes had occurred in lung function over an additional 5-year period.
Findings: Residents of the most
polluted area exhibited normal rates of lung function loss over the retest period. In a separate set of tests,
subjects with the most severe losses in lung function were found to have the same sensitivity to acute ozone exposures
as subjects with less lung function damage.
Importance to ARB's Program: It
was hoped that this study would shed light on chronic effects of exposure to ambient ozone. It did not prove useful
for clarifying this issue; findings of lung function decline proved equivocal. Uncertainties remain with regard
to the chronic effects of air pollution on human health; It is premature to discount the earlier long-term findings.
These uncertainties can only be resolved through further studies with stable funding.
USE OF SPUTUM INDUCTION TO OBTAIN AIRWAY LINING FLUID AFTER
OZONE EXPOSURE: A PILOT STUDY TO VALIDATE SPUTUM INDUCTION AS AN ALTERNATIVE TO BRONCHOSCOPY. Principal Investigator:
JOHN V. FAHY. University of California,
San Francisco. 1995. 92-340.
Objectives: To validate a simple,
safe method (sputum induction) of collecting samples of airway lining fluid and cells from human lungs after exposure
to ozone. The new method would replace the present complicated and invasive procedure, bronchoscopy.
Findings: Physiological responses
to ozone were evident in the lung function measurements. Biochemical indicators of cellular change were found,
indicating cellular damage. Overall, this pilot-level study supports the use of sputum induction as an alternative
to invasive lavage/biopsy methods.
Importance to ARB's Program: Sputum
induction can now be applied to a small cohort of children participating in the ARB's epidemiological study (contract
no. A033-186, 1996) and other clinical studies to determine the effects of repeated and long-term exposures to
pollutants and to understand the sequential course of changes taking place in human lungs.
EVALUATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS
FOR OZONE SENSITIVITY: VALIDATION OF HEALTH ADVISORIES. Principal Investigator: Henry Gong, Jr. M.D. University
of California, Los Angeles. 1995.
A133-123.
Objectives: To determine whether
people with chronic obstructive pulmonary disease (COPD) are more sensitive than healthy humans to low levels of
ozone exposure such as those commonly observed during smoggy days in the Los Angeles area.
Findings: After low-level ozone
exposure, small but statistically significant changes in FEV1 (forced expiratory volume in one second) were found
in both healthy and COPD subjects. Although these changes were small, the effects on the lung function of emphysemics,
who are already at a decreased lung performance level, are considered adverse, since these changes cannot be accommodated
without a health risk.
Importance to ARB's Program: The
results will be useful in evaluating and, if necessary, modifying the health advisories issued by local air pollution
control districts when pollutant levels reach various alert stages.
THE EFFECTS OF OZONE INHALATION ON FIBROBLAST ACTIVATION
IN THE LUNG: POSSIBLE RELATIONSHIP TO LONG-TERM FIBROTIC LUNG CHANGES. Principal Investigator: Homer Boushey, M.D. University of California, San Francisco. 1994. A133-122.
Objectives: To determine whether
ozone exposure stimulates human fibroblasts. (Fibroblasts are lung cells responsible for fibrotic changes, which
can be harmful. While chronic exposure to ozone is known to cause some fibrotic changes in animal lung, there are
no documented studies that similar changes can occur in humans.)
Findings: Ozone exposures were
associated with increased levels of a substance, cytokine, that is implicated in the pathogenesis of lung fibrosis.
Other measures of cellular changes related to fibrosis were not found to increase following ozone exposure.
Importance to ARB's Program: The
results of this study provide a tool to be used in further studies of chronic effects to humans of ozone exposure.
STUDIES OF YOUNG
ADULT FEMALE RESPONSES TO ACUTE OZONE EXPOSURE. Principal Investigator: William C. Adams, Ph.D. University of California,
Davis. 1992.
A933-096 and A033-176.
Objectives: To determine differences
between lung function responses to ozone in healthy women and men during exercise. To confirm the previous observation
that menstrual cycles are disrupted and that women in the early phase of the cycle (when progesterone levels are
lower) respond more strongly than men to ozone.
Findings: Brief single exposures
to Stage II alert levels of ozone (.30 ppm) disrupted some specific hormone responses in over half the women studied.
The changes included surges in estrogen levels in the latter half of the menstrual cycle and delay in ovulation.
Importance to ARB's Program: Further
research including blood hormone levels is needed to understand the implications of these observations before modifying
the health advisories issued during various alert levels for air pollution on smoggy days in the Los Angeles area.
STUDY OF AIR POLLUTION: EFFECTS OF OZONE
ON NEUROPEPTIDE - MEDIATED RESPONSES IN HUMAN SUBJECTS. Principal Investigator: H. A. Baushey, Jr. , M.D. University
of California, San Francisco. 1991. A833-158.
EFFECTS OF OZONE ON CELLULAR SYNTHESIS
AND VIRAL REPLICATION IN VITRO. Principal Investigator: Yuan Chung Zee. University of California, Davis. 1987. A5-153-33.
RELATIONSHIP BETWEEN AIR QUALITY
AND THE RESPIRATORY STATUS OF ASTHMATICS IN AN AREA OF HIGH OXIDANT POLLUTION IN LOS ANGELES COUNTY. School of
Medicine, Los Angeles, CA. 1987. A1-151-33
AND A4-135-33.
PHYSIOLOGICAL RESPONSES OF HEALTHY HUMAN
SUBJECTS CONSEQUENT TO INHALATION OF NO2, O3, AND NO2 PLUS O3 DURING HEAVY, SUSTAINED EXERCISE. Principal Investigator:
William C, Adams, Ph.D. University of California, Davis. 1986. A4-070-33.
CHANGES IN LUNG FUNCTION & EXPOSURE
TO OXIDANTS. Principal Investigator: Roger Detels, MD, MS. University of California, Los Angeles. 1986. A0-133-32.
THE ROLE OF NO2 AND O3 IN CANCER METASTASIS
AND IN SYSTEMIC ADVERSE EFFECTS. Principal Investigator: Arnis Richters, Ph.D. School of Medicine Los Angeles,
CA. 1986. A4-064-33.
EFFECTS OF OZONE ON THE ASTHMATIC AIRWAY.
Principal Investigator: J. A. Nadel, M. D. University of California, San Francisco. 1985. A3-112-33.
HEALTH EFFECTS FROM THE INHALATION OF OXIDANT
AIR POLLUTANTS AS RELATED TO THE IMMUNE SYSTEM. Principal Investigator: John W. Osebold. University of California,
Davis. 1985.
A2-057-33.
THE INFLUENCE OF EXERCISE ON LUNG INJURY
INDUCED BY OZONE AND NITROGEN DIOXIDE. Principal Investigator: William J. Mautz, Ph.D.University of California,
Irvine. 1984.
A2-129-33.
THE EFFECTS OF HEAVY SUSTAINED EXERCISE
IN COMBINATION WITH LOW LEVELS OF OZONE CONCENTRATION IN INDUCING ACUTE PULMONARY FUNCTION IMPAIRMENT IN HUMANS:
INTERACTION OF AMBIENT HEAT AND MULTIPLE POLLUTANT EXPOSURES. Principal Investigator: William C. Adams, Ph.D. University
of California, Davis. 1984. A1-158-33.
HEALTH EFFECTS FROM THE INHALATION OF OXIDANT
AIR POLLUTANTS AS RELATED TO THE IMMUNE SYSTEM. Principal Investigator: John W. Osebold. University of California,
Davis. 1983.
A1-054-32.
AIRWAY RESPONSES TO ATMOSPHERIC POLLUTANTS:
SULFUR DIOXIDE AND OZONE. Principal Investigator: J. A. Nadel, M. D. University of California, San Francisco. 1983. A1-133-33.
OZONE TOXICITY EFFECTS CONSEQUENT TO PROLONGED, HIGH
INTENSITY EXERCISE IN TRAINED ENDURANCE ATHLETES. Principal Investigator: William C. Adams, Ph.D. and Edward S.
Schelegle, M. A. University of California, Davis. 1982. A0-078-32.
EFFECTS OF OZONE INHALATION DURING EXERCISE ON SELECTED
HEART DISEASE PATIENTS. Principal
Investigator: H. Robert Superko, M. D. University of California, Davis. 1981. A8-120-31.
HEALTH
EFFECTS FROM THE INHALATION OF OXIDANT AIR POLLUTANTS AS RELATED TO THE IMMUNE SYSTEM. Principal Investigator:
John W. Osebold. University of California, Davis. 1981. A7-179-30, A8-122-31, and A9-145-31.
AIRWAY HYPERIRRITABILITY INDUCED BY OZONE.
Principal Investigator: J. A. Nadel, M. D. University of California, San Francisco. 1979. A8-053-30.
AIRWAY HYPERIRRITABILITY INDUCED BY OZONE.
Principal Investigator: J. A. Nadel, M. D. University of California, San Francisco. 1978. A6-215-30.
DEVELOPMENT OF A BIOLOGICAL TEST SYSTEM FOR
QUANTITATING THE RESPIRATORY HAZARD OF AMBIENT CONCENTRATIONS OF AIR POLLUTANTS AND EVALUATION OF VITAMIN E IN
THE PREVENTION OF OXIDANT INDUCED IMPAIRMENT. Principal Investigator: Elliot Goldstein, M. D. University of California,
Davis. 1977. 7-077-1.
HEALTH EFFECTS OF OZONE EXPOSURE IN ASTHMATICS.
Principal Investigator: Jack D, Hackney, M. D. Rancho Los Amigos Hospital Inc. 1975. 4-191.
Particulate Matter
POLYCYCLIC AROMATIC HYDROCARBONS (PAHs): SOURCES
OF AMBIENT QUINONES. Principal Investigator: Janet Arey and Roger Atkinson. University of California, Riverside | 