ENVIRONMENTAL AGENTS AND ASTHMA
NIH GUIDE, Volume 23, Number 16, April 29, 1994
PA NUMBER: PA-94-062
P.T. 34
Keywords:
Asthma
Environmental Effects
National Institute of Environmental Health Sciences
National Institute of Allergy and Infectious Diseases
National Heart, Lung, and Blood Institute
PURPOSE
The National Institute of Environmental Health Sciences (NIEHS), the
National Institute of Allergy and Infectious Diseases (NIAID), and
the National Heart, Lung, and Blood Institute (NHLBI) invite
applications to support research to determine the relationships
between exposure to environmental pollutants and allergens and the
induction and/or exacerbation of asthma in humans and to define the
mechanisms by which such environmental agents contribute to the
disease process of asthmatics.
The NIEHS is the principal Federal funding component to support
research scientifically examining the basic mechanisms by which
exposure to physical and chemical agents in the environment have
deleterious effects on human health and exacerbate human health
problems. Many of these agents are airborne substances that
contribute to and/or exacerbate asthma and atopic diseases in
susceptible individuals. The knowledge of mechanisms by which these
agents act will provide the sound scientific basis on which to
develop therapeutic and prophylactic measures for the treatment and
control of these environmentally-induced health problems.
The NIAID is the principal Federal funding component that supports
fundamental research concerned with the structure and function of the
immune system in health and disease. The acquisition of new and
deeper knowledge about the immune system is requisite to the
development of improved procedures for prevention, diagnosis, and
treatment of immunological diseases and diseases having a major
immunological component such as asthma and atopic diseases.
The NHLBI is the principal funding component that supports research
concerned with the structure and function of the pulmonary system in
health and disease. The acquisition of new knowledge on the impact
of inhaled agents on the respiratory system and their role in the
pathogenesis and exacerbation of asthma is requisite to developing
methods for early diagnosis and prevention of disease as well as to
developing new methods for treatment. The research mission of the
NHLBI extends to health education and outreach programs to examine
the environmental impact on lung complications from asthma.
HEALTHY PEOPLE 2000
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas. This PA,
Environmental Factors and Asthma, is related to the priority areas of
environmental health and diabetes and chronic disabling diseases.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report: Stock No. 017-001-00474-0) or "Healthy People 2000"
(Summary Report: Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-0325 (telephone 202-783-3238).
ELIGIBILITY REQUIREMENTS
Research grant applications may be submitted by domestic and foreign,
for-profit and non-profit organizations, public and private, such as
universities, colleges, hospitals, laboratories, units of State or
local governments, and eligible agencies of the Federal government.
Applications from minority individuals and women are encouraged.
Foreign institutions are not eligible to apply for the First
Independent Research Support and Transition (FIRST) Award (R29).
MECHANISM OF SUPPORT
The mechanisms of support will be the individual research project
grant (R01) and the FIRST Award (R29). Multidisciplinary approaches
that involve collaborative efforts among investigators in the fields
of basic and clinical immunology, allergy, pulmonology, biochemistry
and molecular biology are strongly encouraged. Policies that govern
research grant programs of the National Institutes of Health will
prevail.
RESEARCH OBJECTIVES
Background
Asthma is a clinical condition, the symptoms of which include
intermittent shortness of breath and wheezing, chest tightness and
cough. This condition is usually reversible either spontaneously or
as a result of treatment. Asthma may be caused or provoked by
exposure to airborne pollutants encountered in the general
environment or the workplace. Asthma is a common cause of morbidity
and disability, affecting an estimated two to five million children
and 20 million individuals in the USA. Morbidity associated with
asthma accounts for an estimated 8.5 million physician and emergency
room visits annually, this translates into an estimated one million
work days lost that are related to asthma-associated disability.
A large number of agents in the environment and workplace have been
shown to induce asthma and asthma-like syndromes. Although the
proportion of asthma cases and asthma-like illness attributable to
environmental and occupational exposure is currently unknown,
evidence is accumulating that the inhalation of ozone, sulfuric acid,
and nitric acid, by individuals with allergic asthma, significantly
affects their respiratory capacity by decreasing lung volume and peak
flow. The mechanisms responsible for pollutant-induced asthma are
uncertain and the appropriate pharmacologic interventions are
unknown.
A recent report by the Institute of Medicine, supported by the NIAID,
NIEHS, NHLBI and EPA, entitled "The Health Effects of Indoor
Allergens," highlighted the role of indoor allergens in asthma and
provided directions for research to explore this area. The report
reviews recent data suggesting that indoor allergens, notably those
derived from dust mite, cat, and cockroach, are critical factors in
the etiology of asthma, and that individuals spend the vast majority
of their time in an indoor environment, presumably exposed to these
allergens. Indeed, one important, but unproven, theory suggests that
asthma is increasing in prevalence because of changes in house
construction that have made homes "tight," resulting in increased
levels of indoor allergens as well as of other environmental agents
(e.g., irritants such as wood smoke and environmental tobacco smoke).
Outdoor pollutants are relevant as well, since such molecules as
ozone and oxides of nitrogen and sulfur are also present indoors. It
is possible that irritants and pollutants act synergistically with
allergens. The relative importance of these environmental agents are
unknown, but there are several examples of possible interactions
between irritants/pollutants and allergens for influencing both
airway hyperreactivity and immune responses. Ozone and sulfur
dioxide, as mentioned above, are reported to worsen asthma and
increase bronchial hyperreactivity. In animal models these
pollutants (and nitrogen oxides) are said to increase IgE antibody
production. Diesel exhaust particulates apparently enhance IgE
antibody production to allergens. Environmental tobacco exposure not
only reduces pulmonary function, but also appears to enhance IgE
antibody production to allergens. The physicochemical nature of
particulates in the air also are said to regulate IgE antibody
production, perhaps because size, charge, and other properties
influence allergen binding and processing. However, the mechanisms
by which these events occur have not been well characterized. Thus,
this initiative represents a joint effort by NIEHS, NIAID, and NHLBI
to foster research programs to determine such relationships between
exposure to environmental pollutants and allergens and the induction
and/or exacerbation of asthma in humans.
Research Goals and Scope
Areas of research that would be responsive to this Program
Announcement should be focused on mechanistic studies, with both
basic and preclinical investigation, involving animal models,
cultured human cell models, and human patients. These areas may
include, but are not limited to:
o Evaluation of the role of pollutants (including environmental
tobacco smoke, diesel particulates, oxides of nitrogen and sulfur,
and others), in conjunction with allergen on both IgE antibody
production to allergen, and expression of clinical disease.
o Examination of the effects of removal of pollutants and/or
allergen avoidance on reducing IgE antibody responses and preventing
clinical disease.
o Defining the relationship between pollutant-mediated airway
hyperreactivity and allergen-mediated airway hyperreactivity.
o Defining the relationship between outdoor allergens and other
environmental agents in the development and exacerbation of asthma.
o Determining what differences between indoor and outdoor allergens
(and environmental factors such as pollutants) explain why indoor
allergen sensitivity correlates with asthma while outdoor allergen
sensitivity correlates with allergic rhinitis.
o Determining the manner in which pollutants interact with viral
respiratory infections in the induction of asthma.
o Determining the basic mechanisms by which pollutants alter the
inflammatory response in the airways, resulting in airways
hyperreactivity, IgE antibody production and asthma. These studies
could concentrate on the response mechanism which may occur through
the modulation of neural function, epithelial cell function, antigen-
presenting cell function, inflammatory cell function, mediators,
cytokines, receptor modulation, and/or signalling pathways which may
be involved in the pathogenesis of asthma.
STUDY POPULATIONS
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research. This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.
All investigators proposing research involving human subjects read
the "NIH Guidelines For Inclusion of Women and Minorities as Subjects
in Clinical Research," which have been published in the Federal
Register of March 9, 1994 (FR 59 11146-11151) and reprinted in the
NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18,
1994.
Investigators also may obtain copies of the policy for the program
staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.
Animal Welfare Considerations
Investigators are encouraged to consider alternative methods and
approaches in their research applications that do not require the use
of whole animals, use alternative species such as nonmammals or
invertebrates, reduce the number of animals required, and incorporate
refinements to procedures that will result in the elimination or
further minimization of pain and distress to animals.
APPLICATION PROCEDURES
Applications are to be submitted on form PHS 398 (rev. 9/91), which
is available in the office of sponsored research at most academic and
research institutions and from the Office of Grants Information,
Division of Research Grants, National Institutes of Health, Westwood
Building, Room 449, Bethesda, MD 20892, telephone 301/594/-7248. To
identify the application as a response to this program announcement,
check "YES" in Item 2a on the face page of the application and enter
the program announcement title and number. Applications will be
accepted in accordance with the usual receipt dates for new research
grant applications, i.e., February 1, June 1, and October 1. The
earliest possible award dates will be approximately nine months after
the respective receipt dates. Applications received too late for one
cycle of review will be held until the next receipt date.
Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application. FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review. Applications will be received
by the NIH Division of Research Grants (DRG) and referred to an
appropriate study section for scientific and technical merit review.
Institute assignment decisions will be governed by normal
programmatic considerations as specified in the NIH Referral
Guidelines.
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research. If so, a letter of agreement from either the
GCRC program director or principal investigator should be included
with the application.
The original and five copies of the application must be sent to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
REVIEW CONSIDERATIONS
The review criteria customarily employed by the NIH for regular
research grant applications will prevail. Following the initial
scientific review, the applications will be evaluated by the
appropriate National Advisory Council.
AWARD CRITERIA
Applications will compete for available funds with all other approved
applications assigned to that ICD. The following will be considered
in making funding decisions: quality of the proposed project as
determined by peer review, availability of funds, program balance
among research areas of the announcement.
INQUIRIES
Written and telephone inquiries are encouraged. The opportunity to
clarify any issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
George S. Malindzak, Jr., Ph.D.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
104 T.W. Alexander Drive
P.O. Box 12233
Research Triangle Park, NC 27709
Telephone: (919) 541-3289
FAX: (919) 541-2843
Marshall Plaut M.D.
Asthma and Allergy Branch
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A23
Bethesda, MD 20892
Telephone: (301) 496-8973
FAX: (301) 402-2571
Suzanne S. Hurd, Ph.D.
Division of Lung Diseases
National Heart, Lung and Blood Institute
Westwood Building, Room 6416
Bethesda, MD 20892
Telephone: (301) 594-7430
FAX: (301) 594-7408
Direct inquiries regarding fiscal matters to:
David L. Mineo
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233
Research Triangle Park, NC 27709
Telephone: (919) 541-1373
Jeffrey Carow
Immunology Grants Management Section
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B29
Bethesda, MD 20892
Telephone: (301) 496-7075
Mr. Raymond L. Zimmerman
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 4A11C
Bethesda, MD 20892
Telephone: (301) 594-7430
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic
Assistance Numbers 93.112, Characterization of Environmental Health
Hazards, 93.113, Biological Response to Environmental Health Hazards,
and 93.855, Allergy, Immunology and Transplantation Research. Awards
are made under the authority of Section 487, Public Health Service
Act as amended (42 USC 288) and administered under PHS Grants
Policies and Title 42 of the Code of Federal Regulations, Part 66.
This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency
review.
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