NIH GUIDE, Volume 22, Number 2, January 15, 1993

PA NUMBER:  PA-93-37

P.T. 34




  Biology, Molecular 

  Biomedical Research, Multidiscipl 

National Institute of Allergy and Infectious Diseases

National Heart, Lung and Blood Institute


The Division of Allergy, Immunology, and Transplantation (DAIT) of

the National Institute of Allergy and Infectious Diseases (NIAID) and

the Division of Lung Diseases (DLD) of the National Heart, Lung, and

Blood Institute (NHLBI) invite applications for support of basic and

preclinical studies designed to define the role of T cell subsets and

the cytokines that they secrete in the inflammation that is

characteristic of both clinical asthma and the late phase reactions

following bronchial challenge with antigen.


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 Program

Announcement, Asthma as a T-cell-mediated Disease, is related to the

priority area of 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



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 and

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).


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




The etiology of asthma remains poorly understood.  A series of

studies have recently  emphasized that asthma is an inflammatory

disease of the airways, and that reducing inflammation is critical

for successful management of severe asthma.  The inflammatory cells

include increased numbers of eosinophils, basophils and T

lymphocytes.  Of particular interest from the standpoint of new

approaches to the pathogenesis of asthma is the involvement of T

lymphocytes.  In allergic asthma, the inflammatory T cells express

TH2-like lymphokines [i.e., IL-4 and IL-5 but not interferon-~

(IFN)].  Both IL-4 and IL-5 appear to be critically important to

allergic inflammation.

The universality of these findings in all asthmatics is

controversial.  Some data suggest that so-called "intrinsic"

asthmatics (who have low total IgE levels and no IgE antibodies to

known allergens) express the cytokines IL-5 and IFN, that are not

characteristic of known T-cell subsets.  In contrast, other data

indicate that all asthmatics, including non-atopic asthmatics, have

higher total levels of IgE than non-asthmatics; high levels of IgE

presumably are associated with increased production of IL-4.  The

elevated levels of IgE may represent IgE antibody to allergen(s).

Indeed, production of IgE antibodies to specific allergens, notably

indoor allergens derived from dust mite, cat and cockroach, is

characteristic of a substantial proportion of asthmatics and measures

which reduce exposure to these allergens result in asthma


Research Objectives and Scope - To elucidate the importance of T

cells in the etiology of asthma, the NIAID and the NHLBI are

soliciting individual research project grants that are designed to

define the role of T cell subsets and their secreted products in the

inflammatory processes associated with asthma.  Such studies may

include but are not limited to:

o  Biochemical and molecular characterization of bulk and antigen-

specific T lymphocyte populations in lung and blood, including

evaluation of such parameters as T-cell receptors, adhesion

molecules, and patterns of cytokine expression

o  Correlation between T-cell populations and clinical and

immunological patient parameters such as asthma severity, and levels

of antigen-specific and total serum IgE, basophil and eosinophil

accumulation and activation, and airways reactivity.

o  Determination of the effects on T-cell populations of agents

useful in treatment of allergic diseases and asthma, such as allergen

immunotherapy and glucocorticosteroids.

The use of modern, state-of-the-art technology in biochemistry and

molecular biology in these projects would be of great value.





NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women

in study populations so that research findings can be of benefit to

all persons at risk of the disease, disorder or condition under

study; special emphasis must be placed on the need for inclusion of

minorities and women in studies of diseases, disorders and conditions

that disproportionately affect them.  This policy is intended to

apply to males and females of all ages.  If women or minorities are

excluded or inadequately represented in clinical research,

particularly in proposed population-based studies, a clear compelling

rationale must be provided.

The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of

the study.  This information must be included in the form PHS 398 in

items 1-4 of the Research Plan AND summarized in item 5, Human

Subjects.  Applicants are urged to assess carefully the feasibility

of including the broadest possible representation of minority groups.

However, NIH recognizes that it may not be feasible or appropriate in

all research projects to include representation of the full array of

United States racial/ethnic minority populations (i.e., Native

Americans (including American Indians or Alaskan Natives),

Asian/Pacific Islanders, Blacks, Hispanics).  The rationale for

studies on single minority population groups must be provided.

For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology,

prevention (and preventive strategies), diagnosis, or treatment of

diseases, disorders or conditions, including but not limited to

clinical trials.

The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including


If the required information is not contained within the application,

the review will be deferred until the information is provided.  Peer

reviewers will address specifically whether the research plan in the

application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and will be

reflected in assigning the priority score to the application.

All applications for clinical research submitted to NIH are required

to address these policies.  NIH funding components will not award

grants or cooperative agreements that do not comply with these



Applicants are to use the research grant application form PHS 398

(rev. 9/91).  For purposes of identification and processing, check

yes on item 2a of the face page and enter the PA number and title:

"PA-93-37: Asthma as a T-cell-mediated Disease".  Applications will

be accepted in accordance with the standard submission dates for new

applications: February 1, June 1, and October 1.

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.

Application kits are available at most institutional offices of

sponsored research and may be obtained from the Office of Grants

Inquiries, Division of Research Grants, National Institutes of

Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone

(301) 496-7441.

The completed signed original application and five legible copies

must be sent or delivered to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**

For FIRST award (R29) applications, three reference letters (in

sealed envelopes) must be attached to the face page of the original

application and submitted with the application.  Failure to provide

the three reference letters will result in return of the application

to the investigator.


Applications will be assigned on the basis of established PHS

referral guidelines.  Applications will be reviewed for scientific

and technical merit by study sections of the Division of Research

Grants (DRG), NIH, in accordance with the standard NIH peer review

procedures.  Following scientific-technical review, the applications

will receive a second-level review by an appropriate national

advisory council or board.


Applications will compete for available funds with all other approved

applications.  The following will be considered in making funding

decisions: quality of the proposed project as determined by peer

review, availability of funds, and program balance among research

areas of the announcement.


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:

Marshall Plaut, M.D.

Division of Allergy, Immunology and Transplantation

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4A23

Bethesda, MD  20892

Telephone: (301) 496-8973

FAX:  (301) 402-2571

Susan P. Banks-Schlegel, Ph.D.

Division of Lung Diseases

National Heart, Lung and Blood Institute

Westwood Building, Room 6A15

Bethesda, MD  20892

Telephone:  (301) 496-7332

FAX:  (301) 496-9886

Direct inquiries regarding fiscal matters to:

Mr. Jeffrey Carow

Immunology Grants Management Section

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4B29

Bethesda, MD  20892

Telephone:  (301) 496-7075

Tanya McCoy

Division of Extramural Affairs

National Heart, Lung and Blood Institute

Westwood Building, Room 4A17A

Bethesda, MD  20892

Telephone:  (301) 496-4970


This program is described in the Catalog of Federal Domestic

Assistance, No. 93.855 and No. 93.838.  Grants are awarded under the

authority of the Public Health Service Act, Section 301 (42 USC 241)

and Title IV, Part A (Public Law 78-410, as amended by Public Law

99-158, 42 USC 241 and 285) and administered under PHS grants

policies and Federal Regulations, most specifically at 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 Agency review.


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