Full Text PA-97-078
 
INFLAMMATION IN ASTHMA AND ALLERGY
 
NIH GUIDE, Volume 26, Number 24, July 25, 1997
 
PA NUMBER:  PA-97-078
 
P.T. 34

Keywords: 
  Asthma 
  Inflammation 
  Hypersensitivity 

 
National Institutes of Health
 
PURPOSE
 
The purpose of this asthma and allergy research Program Announcement
(PA) is to inform the scientific community of the interests of NIH
Institutes in stimulating a wide range of basic and clinical studies
to: characterize the role of tissue inflammation in the pathogenesis
of asthma and allergic diseases; identify factors responsible for the
initiation and maintenance of inflammation in asthma and allergic
diseases; and, based on this knowledge, develop new and improved
approaches to treat and prevent these disorders.  The funding
mechanisms to be used to support research under this PA are R01s and
R29s.
 
HEALTHY PEOPLE 2000
 
Each NIH PA addresses one or more of 22 Health Promotion and Disease
Prevention priority areas identified.  These areas can be found via
the WWW at URL:  http://www/crisny.org/health/us/health7.html
 
ELIGIBILITY
 
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 and local
governments, and eligible agencies of the Federal government. Foreign
institutions are not eligible for FIRST awards (R29).  Racial/ethnic
minority individuals, women, and persons with disabilities are
encouraged to apply as Principal Investigators.
 
MECHANISM OF SUPPORT
 
Traditional research project grant (R01) and FIRST award (R29)
applications may be submitted in response to this program
announcement.  Applications for R01 grants may request up to five
years of support and applications for R29 grants must request five
years of support.  Responsibility for the planning, direction, and
execution of the proposed research for all applicable mechanisms of
support will be solely that of the applicant.
RESEARCH OBJECTIVES
 
Background
 
This PA will support studies of the underlying mechanisms of
inflammation in asthma and allergic diseases. Chronic inflammation of
the airways is now recognized as a primary factor in the development
of asthma and anti-inflammatory medications, especially inhaled
steroids, have become a mainstay of asthma therapy.  However, even
medically well-controlled asthmatics are subject to exacerbations
that are difficult to treat, and it is likely that insights into the
pathogenesis of inflammation will lead to more effective and safer
therapies for asthma and allergic diseases.
 
Research Objectives and Scope
 
Recent studies have demonstrated the importance of previously
unrecognized pathways leading to tissue inflammation in asthma and
allergic diseases.  For example, "upper" respiratory viral infections
were recently shown to induce widespread airway inflammation in
humans and are now known to be the most common cause of severe
asthmatic exacerbations.  However, the cellular and molecular
mechanisms by which viruses elicit airway inflammation are largely
unknown.  In epidemiologic and genetic studies, investigators have
identified a number of promising candidate genes and genetic loci
that are related to asthma, airway hyperresponsiveness, and atopy.
In several instances, the candidate genes encode proteins known to be
involved in the evolution of inflammatory responses.  Thus, genetic
studies may help to identify new therapeutic targets for asthma and
allergic diseases.  In addition, genetic approaches may ultimately
enable clinicians to target individual therapies more selectively in
specific patient populations and to develop mechanism-based
strategies for primary prevention.
 
Certain technological advances and recently developed tools can also
be expected to facilitate progress in these areas. These include: (1)
the ability to directly visualize the airways by fiberoptic
bronchoscopy and to routinely obtain bronchoalveolar lavage fluids
and inflammatory cells for study; (2) the advent of better animal
models that more closely mimic the altered immune function in human
asthma; and (3) the availability of transgenic and gene knockout
animals to test the importance of specific mediators, receptors, and
signaling pathways in the induction of tissue inflammation.
 
Examples of research topics of interest include, but are not limited
to, the following:
 
Allergic Mechanisms
 
o identification and characterization of genes that regulate the
production of IgE and the clinical expression of asthma and atopy;
 
o structural analysis and recombinant molecular engineering of
allergen epitopes to develop new approaches for immune modulation;
 
Non-Allergic Mechanisms
 
o studies to define the immune mechanisms of virus-mediated airway
inflammation and bronchial hyperactivity in asthma;
 
o studies on the role of environmental agents, including aromatic
hydrocarbons, ozone, and nitrogen dioxide, in the induction of airway
inflammation and their role in asthma;
 
Combined Allergic and Non-Allergic Mechanisms
 
o studies of chemokines in asthma;
 
o studies to determine the mechanisms that lead to differential
induction of Th1 and Th2 responses, and development of strategies to
manipulate Th1 and Th2 responses for treatment or prevention of
asthma and allergic diseases;
o studies on the induction and primary prevention of asthma; and
 
o research on factors that control the persistence or cessation of
inflammation in the context of asthma and allergic diseases.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
See NIH Guide of March 18, 1994 for requirements for inclusion of
Women and Minorities in research.  It is available via the WWW at
URL: http://www.nih.gov/grants (select NIH Guide for Grants and
Contracts).
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application for PHS 398
(rev. 5/95) and will be accepted on the standard application
deadlines as indicated on the application kit.  Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Office of Extramural Outreach and Information,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone (301) 710-0267, email:
asknih@odrockm1.nih.gov.  The PHS 398 application kit can be accessed
from the World Wide Web at the following URL:
http://www.nih.gov/grants/funding/phs398/phs398.html
 
For purposes of identification and processing, item 2 on the face
page of the application must be marked "YES".  The PA number, the PA
title must be typed in section 2.
 
The completed, signed original and five legible, single-sided copies
of the application must be sent or delivered to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817-7710 (for express/courier service)
 
R29 applications must include at least three (3) sealed letters of
reference attached to the face page of the original application.
FIRST applications submitted without the required number of reference
letters will be considered incomplete and will be returned without
review.
 
ALL APPLICANTS REQUESTING $500,000 OR MORE IN ANNUAL DIRECT COSTS.
The NIH Policy Update on Acceptance for Review of Unsolicited
Applications that Request More Than $500,000 Direct Cost for Any One
Year applies to applications in response to this PA.  The Policy
Update was published in the NIH Guide for Grants and Contracts,
Volume 25, No. 14, May 3, 1996, and became effective June 1, 1996.
Potential applicants must contact the appropriate program staff
listed in INQUIRIES below to initiate clearance processes for
acceptance of their applications.
 Applicants from institutions that have a General Clinical Research
Centers (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the Center as a resource for
conducting the proposed research.  If so, a letter of agreement from
the GCRC Program Director must be included in the application
material.
 
REVIEW CONSIDERATIONS
 
Review Procedures
 
Applications will be assigned to NIH Institutes and Centers on the
basis of established PHS referral guidelines. Upon receipt,
applications will be reviewed for completeness by the NIH Division of
Research Grants.  Incomplete applications will be returned to the
applicant without further consideration.
 
Applications will be reviewed for scientific and technical merit by
study sections of the Division of Research Grants, NIH, in accordance
with the standard NIH peer review procedures.  As part of the initial
merit review, all applications will receive a written critique and
undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed, assigned a priority score, and
receive a second level review by the appropriate national advisory
council.
 
Review Criteria
 
The five criteria to be used in the evaluation of grant applications
are listed below.
 
The goals of NIH-supported research are to advance our understanding
of biological systems, improve the control of disease, and enhance
health.  The reviewers will be asked to comment on the following
aspects of the application in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of
these goals.  Each of these criteria will be addressed and considered
by the reviewers in assigning the overall score weighting them as
appropriate for each application.  Note that the application does not
need to be strong in all categories to be judged likely to have a
major scientific impact and thus deserve a high priority score.  For
example, an investigator may propose to carry out important work that
by its nature is not innovative but is essential to move a field
forward.
 
1.  SIGNIFICANCE.  Does this study address an important problem? If
the aims of the application are achieved, how will scientific
knowledge be advanced?  What will be the effect of these studies on
the concepts or methods that drive this field?
 
2.  APPROACH.  Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to
the aims of the project?  Does the applicant acknowledge potential
problem areas and consider alternative tactics?
 
3.  INNOVATION.  Does the project employ novel concepts, approaches
or method?  Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
 
4.  INVESTIGATOR.  Is the investigator appropriately trained and well
suited to carry out this work?  Is the work proposed appropriate to
the experience level of the principal investigator and other
researchers (if any)?
 
5.  ENVIRONMENT.  Does the scientific environment in which the work
will be done contribute to the probability of success?  Do the
proposed experiments take advantage of unique features of the
scientific environment or employ useful collaborative arrangements?
Is there evidence of institutional support?
 
The initial review group will also examine: the appropriateness of
proposed project budget and duration;  the adequacy of plans to
include both genders and minorities and their subgroups as
appropriate for the scientific goals of the research and plans for
the recruitment and retention of subjects; the provisions for the
protection of human and animal subjects; and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other
favorably recommended applications.  The following will be considered
when making funding decisions: quality of the proposed project as
determined by peer review, program balance, and availability of
funds.
 
SPONSORS AND INQUIRIES
 
Each sponsoring Institute/Center is identified below.  A staff
contact for electronic and telephone is listed and inquiries
regarding programmatic (research scope, eligibility and
responsiveness) issues are encouraged.  The opportunity to clarify
any issues or answer questions from potential applicants is welcome.
 
National Institute of Allergy and Infectious Diseases
Daniel Rotrosen, M.D.
Telephone: (301) 496-8974
Fax:       (301) 402-0175
Email:     dr17g@nih.gov
 
National Heart, Lung, and Blood Institute
Susan Banks-Schlegel, Ph.D.
Telephone: (301) 435-0202
Fax:         (301) 480-3557
Email:  Susan_Banks-Schlegel@nih.gov
 
National Institute of Environmental Health Sciences
George S. Malindzak, Jr., Ph.D.
Telephone:  (919) 541-3289
Telefax:    (919) 541-2843
Email Address:  gm26f@nih.gov
 
AUTHORITY AND REGULATIONS
 
Research under this announcement will be supported under program
cited in the Catalog of Federal Assistance (CFDA).  The PHS portion
of the CFDA is available at URL:
http://odphp.osophs.dhhs.gov/cfda/index.htm
 
Awards will be administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74.  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems review.
 
The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.
 
.

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