EFFECTS OF MIXED DUSTS ON PULMONARY INFLAMMATION, AIRWAY REACTIVITY AND 
SUSCEPTIBILITY TO PULMONARY INFECTION

Release Date:  February 28, 2000

RFA:  OH-00-009

National Institute for Occupational Safety and Health (NIOSH)

Letter of Intent Receipt Date:  March 28, 2000
Application Receipt Date:       April 24, 2000

PURPOSE

The National Institute for Occupational Safety and Health (NIOSH), 
Centers for Disease Control and Prevention (CDC), invites 
applications for a collaborative investigation that will 
contribute information concerning the adverse pulmonary effects of 
mixed dusts (such as, welding fume, boiler ash, diesel exhaust 
particles, etc.).  The overall goal of this program is to foster 
multidisciplinary studies which integrate molecular, cellular, 
animal and human approaches to determine the role of workplace 
exposure to mixed dusts on the initiation of obstructive lung 
disease and the enhancement of susceptibility to pulmonary 
infection.  Toward this goal, this Request for Applications (RFA) 
encourages scientific investigation to determine the harmful 
components of mixed dusts which contribute to adverse pulmonary 
reactions and to elucidate mechanisms in which pulmonary morbidity 
is initiated.

HEALTHY PEOPLE 2010

CDC is committed to achieving the health promotion and disease 
prevention objectives of AHealthy People 2010,@ a national 
activity to reduce morbidity and mortality and improve the quality 
of life.  This announcement is related to the focus area of 
occupational safety and health.  For information on the conference 
on AHealthy People 2010,@  visit the internet site: 
http://www.health.gov/healthypeople.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by public and private nonprofit and 
for-profit organizations and by governments and their agencies, 
that is, universities, colleges, research institutions, hospitals, 
other public and private nonprofit and for-profit organizations, 
State and local governments or their bona fide agents, including 
small, minority and/or women-owned businesses.  Applications from 
minority and women investigators are encouraged.

For foreign organizations, special review criteria apply.  Refer 
to the following internet site: 
http://grants.nih.gov/grants/policy/gps/app4.htm

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for this 
program will be a cooperative agreement (U01), an "assistance" 
mechanism (rather than an "acquisition" mechanism), in which 
substantial NIOSH scientific and/or programmatic involvement with 
the awardee is anticipated during performance of the activity.  
The awardee will be responsible for the planning, direction, and 
execution of the proposed project and interrelated activities.  
The NIOSH purpose is to support and/or stimulate the recipient"s 
activity by involvement in and otherwise working jointly with the 
award recipient, but it is not to assume direction, prime 
responsibility, or a dominant role in the activity.  Details of 
the responsibilities, relationships and governance of the study to 
be funded under cooperative agreement(s) are discussed later in 
this document under the section "Terms and Conditions of Award."

The total project period for an application submitted in response 
to this present RFA may not exceed 3 years.  The anticipated award 
date is September 1, 2000.  The award and level of support depends 
on receipt of applications of high scientific merit. 

FUNDS AVAILABLE

Approximately $200,000  is available in FY 2000 to fund one award. 

Continuation award within an approved project period will be made 
on the basis of satisfactory progress as evidenced by required 
reports and the availability of funds.

USE OF FUNDS

Recipient should allocate funds for travel for two project staff 
to attend semiannual one-to two-day meetings in Morgantown, West 
Virginia for each year of the project.   

PREAPPLICATION CONFERENCE

Applicants are invited by NIOSH to attend a pre-application 
technical assistance conference on Wednesday, March 15, 2000 at 
1:00 PM (Eastern time) to discuss:  programmatic issues regarding 
this program, including suggested research partners, how to apply, 
and questions regarding the content of the RFA.  This conference 
is expected to last approximately two hours.  The conference will 
be held in Room L3B, Health Effects Laboratory Division, NIOSH, 
located at 1095 Willowdale Road, Morgantown, West Virginia 26505. 
Applicants may also participate by telephone.  The conference name 
is ANIOSH Mixed Dusts.@  The telephone bridge number is (800) 311-
3437.  Participants will need the conference code, 301248, to be 
connected.

RESEARCH OBJECTIVES

Background

The National Occupational Research Agenda states that workers in 
numerous occupations are commonly exposed to mixed dusts.  
Examples of mixed dusts include: welding fumes, boiler ash, diesel 
exhaust particles, etc.  At present, knowledge concerning the 
potential adverse pulmonary effects of exposure to mixed dusts is 
limited.  In addition, understanding is limited with respect to 
the possible synergistic effects of the particulate and chemical 
components of mixed dusts.

Epidemiologic studies have suggested a link between pulmonary 
morbidity and exposure to ambient particulate matter.  Pulmonary 
effects include: exacerbation of obstructive lung diseases, such 
as asthma and bronchitis, and an increased susceptibility to 
pulmonary infections.  However, explanations as to the reason(s) 
why exposure to particulate matter at relatively low (ambient) 
levels leads to such adverse pulmonary effects are lacking.  
Current research efforts have concentrated on possible chemical 
components associated with ambient particulate matter.  Hypotheses 
concerning the etiologic components include: metals, organic 
chemicals, and acidity associated with respirable particles from 
various sources.  It has been proposed that such components of 
mixed dusts may enhance cell damage and induce the production of 
inflammatory cytokines in the airways.  Oxidant injury and 
inflammation have been associated with increased mucus production 
and/or increased airway smooth muscle reactivity related to 
bronchitis and asthma, respectively.  Other studies have suggested 
that components of mixed dusts can impair bacterial killing by 
lung phagocytes and may lead to an increased incidence of 
pulmonary infections.  Clearly more information is needed to 
elucidate the role of these components and understand mechanisms 
which lead to pulmonary disease.

Data discussed above suggest that exposure to mixed dusts at 
ambient levels is a pulmonary health concern,  therefore, workers 
exposed to much higher levels of mixed dusts may be at risk.  
Estimates indicate that as many as 1 million US workers in 
construction, transportation, mining, and other industries have at 
least part-time exposures to mixed dusts.  There is a need to 
evaluate exposures of various working cohorts, determine the 
components associated with these mixed dusts, and document if 
adverse pulmonary effects are prevalent in exposed workers.  Data 
gaps also exist in elucidating which particulate components are 
important and determining the molecular and cellular mechanisms 
involved in initiation and progression of adverse pulmonary 
effects.  Cellular and animal models may be useful in developing 
mechanistic frameworks which can be extrapolated to humans.

Research Goals and Objectives

The objective of this RFA is to foster research to determine the 
pulmonary effects of exposure of a worker population to mixed 
dusts(s).  Pulmonary effects of concern include but are not 
limited to initiation of obstructive lung diseases and enhancement 
of susceptibility to pulmonary infection.  Of interest is the 
collection of human data on a worker cohort which would assist in 
determining which components of mixed dusts play a role in human 
disease initiation or exacerbation.  Also of interest is 
information concerning the relationship between dose/duration in 
pulmonary response in these exposed workers.  Evaluation of 
indices of inflammation in biological samples (e.g. nasal lavage, 
blood, sputum, exhaled air, etc.) may be useful in elucidation of 
mechanisms of action.  It is anticipated the integration of human 
studies with complimentary molecular, cellular and/or animal 
studies would be valuable in elucidating etiologic components and 
pathologic mechanisms.  Therefore, a multidisciplinary approach is 
encouraged.

SPECIAL REQUIREMENTS

Applicants must document the availability of a cohort of workers 
exposed to mixed dusts.  In addition, applications taking 
advantage of existing worker populations are encouraged.

TERMS AND CONDITIONS OF AWARD

The Terms and Conditions of Award, below, will be incorporated in 
all awards issued as a result of this RFA.  It is critical that 
each applicant include specific plans for responding to these 
terms.  These special Terms of Award are in addition to and not in 
lieu of otherwise applicable OMB administrative guidelines, HHS 
Grant Administration Regulations at 45 CFR Parts 74 and 92, and 
PHS Grants Policy Statement.  The administrative and funding 
instrument used for this program will be a cooperative agreement 
(U01), an "assistance" mechanism (rather than an "acquisition" 
mechanism) in which substantial NIOSH scientific and/or 
programmatic involvement with the awardee is anticipated during 
performance of the activity.

Under the cooperative agreement, the NIOSH purpose is to support 
and/or stimulate the recipient"s activity by involvement in and 
otherwise working jointly with the award recipient in a partner 
role, but it is not to assume direction, prime responsibility, or 
a dominant role in the activity.  Consistent with this concept, 
the dominant role and prime responsibility for the activity 
resides with the awardee for the project as a whole, although 
specific tasks and activities in carrying out the studies may be 
shared among the awardee and the NIOSH Project Scientist where 
appropriate, including the following:

1. Recipient Responsibilities

The recipient will coordinate project activities, scientifically 
and administratively, at the awardee institution and at other 
sites that may be supported by sub-contractors to this award.  The 
recipient will have primary authority and responsibility to define 
objectives and approaches, and to plan, conduct, analyze, and 
publish results, interpretations, and conclusions of studies 
conducted under the terms and conditions of the cooperative 
agreement award.  Recipient will: 

a.  enroll and follow-up the study participants and establish and 
maintain mechanisms to ensure that data collection and management 
procedures have necessary quality control and confidentiality of 
data,				

b.  provide study participants with individual notification 
letters when medical tests are performed, 

c.  develop and submit semiannual progress reports,

d.  disseminate the scientific findings,  				

e.  provide program management and oversight for the project, 

f.  notify study participants of the overall study results, and 

g.  participate in semi-annual meetings to provide information on 
program status. 

2.  NIOSH Responsibilities

The NIOSH Project Scientist may, at the request of the recipient, 
provide substantial scientific-programmatic involvement during 
conduct of this activity, through technical assistance, advice, 
and coordination.  

a.  provide expert consultation in the area of exposure 
monitoring, particle analysis, and pulmonary toxicology,

b.  provide technical advice on monitoring of dust levels, airway 
reactivity, pulmonary inflammation, and antimicrobial potency,

c.  facilitate collaborative efforts to compile and disseminate 
program results through presentations and publications,

d.  assist in the development of human subjects protocols for the 
CDC Institutional Review Board (if required) and in the 
preparation of OMB (and other) clearances that may be required 
during the conduct of the study.

PAPERWORK REDUCTION ACT

Projects that involve the collection of information from 10 or 
more individuals and funded by cooperative agreement will be 
subject to review and approval by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act.

HUMAN SUBJECTS REQUIREMENTS

If a project involves research on human subjects, assurance (in 
accordance with Department of Health and Human Services 
Regulations, 45 CFR Part 46) of the protection of human subjects 
is required.  In addition to other applicable committees, Indian 
Health Service (IHS) institutional review committees also must 
review the project if any component of IHS will be involved with 
or will support the research.  If any American Indian community is 
involved, its tribal government must also approve that portion of 
the project applicable to it.  Unless the awardee holds a Multiple 
Project Assurance, a Single Project Assurance is required, as well 
as an assurance for each subcontractor or cooperating institution 
that has immediate responsibility for human subjects.  The Office 
for Protection from Research Risks (OPRR) at the National 
Institutes of Health negotiates assurances for all activities 
involving human subjects that are supported by the Department of 
Health and Human Services.

ANIMAL SUBJECTS REQUIREMENTS

If the proposed project involves research on animal subjects, 
compliance with the "PHS Policy on Humane Care and Use of 
Laboratory Animals by Awardee Institutions" is required.  An 
applicant (as well as each subcontractor or cooperating 
institution that has immediate responsibility for animal subjects) 
proposing to use vertebrate animals in CDC-supported activities 
must file (or have on file) the Animal Welfare Assurance with the 
Office for the Protection from Research Risks (OPRR) at the 
National Institutes of Health. The applicant must provide in the 
application the assurance of compliance number and evidence of 
review and approval (including the date of the most recent 
approval) by the Institutional Care and Use Committee (IACUC).

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN 
SUBJECTS

It is the policy of the Centers for Disease Control and Prevention 
(CDC) to ensure that individuals of both sexes and the various 
racial and ethnic groups will be included in CDC-supported 
research projects involving human subjects, whenever feasible and 
appropriate. Racial and ethnic groups are those defined in OMB 
Directive No. 15 and include American Indian or Alaska Native, 
Asian, Black or African American, Hispanic or Latino, Native 
Hawaiian or Other Pacific Islander.  Applicants shall ensure that 
women, racial and ethnic minority populations are appropriately 
represented in applications for research involving human subjects. 
 Where clear and compelling rationale exist that inclusion is 
inappropriate or not feasible, this situation must be explained as 
part of the application.  This policy does not apply to research 
studies when the investigator cannot control the race, ethnicity, 
and/or sex of subjects.  Further guidance to this policy is 
contained in the Federal Register, Vol. 60, No. 179, pages 
47947-47951, and dated Friday, September 15, 1995. 

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS 
PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the 
age of 21) must be included in all human subjects research, 
conducted or supported by NIH, unless there are clear and 
compelling reasons not to include them.  This policy applies to 
all initial (Type 1) applications submitted for receipt dates 
after October 1, 1998.  This policy will be followed by NIOSH for 
this announcement. 

All investigators proposing research involving human subjects 
should read the "NIH Policy and Guidelines on the Inclusion of 
Children as Participants in Research Involving Human Subjects" 
that was published in the NIH Guide for Grants and Contracts, 
March 6, 1998, and is available at the following URL address:  
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators may also obtain copies of the policy from the 
program staff listed under INQUIRIES.  Program staff may also 
provide additional relevant information concerning the policy.

LETTER OF INTENT 

Prospective applicants are asked to submit, by March 28, 2000, a 
letter of intent that includes a descriptive title of the proposed 
research, name, address, and telephone number of the Principal 
Investigator, identities of other key personnel and participating 
institutions, and number and title of the RFA in response to which 
the application may be submitted.

Although a letter of intent is not required, is not binding, and 
does not enter into the review of subsequent applications, the 
information allows NIOSH staff to estimate the potential review 
workload and to avoid conflict of interest in the review.

The letter of intent is to be sent to: 

Ann M. Cronin
National Institute for Occupational Safety and Health (NIOSH)
Centers for Disease Control and Prevention (CDC) 
1600 Clifton Road, NE
Mailstop D40

Building 1, Room 3070B
Atlanta, GA 30333
Telephone: 404/639-2277
Fax: 404/639-0035
Email: [email protected]

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be 
used in applying for this cooperative agreement.  Applications 
kits are available at most institutional offices of sponsored 
research and may be obtained from the Division of Extramural 
Outreach and Information Resources, National Institutes of Health, 
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 
301/710-0267, E-mail: [email protected].  Applications are also 
available on the web at: http://grants.nih.gov/grants/forms.htm.

The RFA label available in the PHS 398 (rev. 4/98) application 
form must be affixed to the bottom of the face page of the 
application.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the 
review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the 
application form and the YES box must be marked.

A sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been 
modified to allow for this change.  Please note this is in pdf 
format.

A detailed timetable for the proposed study must be included in 
the application.

Submit a signed, typewritten original of the application, 
including the Checklist, and three signed photocopies, in one 
package to:

CENTER FOR SCIENTIFIC REVIEW (CSR)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the 
application must also be sent to:

Ann M. Cronin
National Institute for Occupational Safety and Health (NIOSH)
Centers for Disease Control and Prevention (CDC) 
1600 Clifton Road, NE
Mailstop D40
Building 1, Room 3070B
Atlanta, GA 30333

Applications must be received by April 24, 2000.  If an 
application is received after that date, it will be returned to 
the applicant without review.  The Center for Scientific Review 
(CSR) will not accept any application in response to this RFA that 
is essentially the same as one currently pending initial review, 
unless the applicant withdraws the pending application.  CSR will 
not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of a 
substantial revision of an application already reviewed, but such 
an application must follow the guidance in the PHS Form 398 
application instructions for the preparation of revised 
applications, including an introduction addressing the previous 
critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by 
CSR and responsiveness by NIOSH.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.  Those applications that are complete and 
responsive will undergo further scientific merit review in 
accordance with the criteria stated below for scientific/technical 
merit by an appropriate peer review group convened by NIOSH.  The 
second level of review will be provided by the NIOSH Secondary 
Review Panel. 

All applications will be judged on the basis of the scientific 
merit of the proposed project and the documented ability of the 
investigators to meet the RESEARCH OBJECTIVES of the RFA.  
Although the technical merit of the proposed protocol is 
important, it will not be the sole criterion for evaluation of a 
study.  Access to the study population and ability to achieve the 
initiative=s goals will also be part of the evaluation criteria.  

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 NIOSH Secondary Review Panel. 

PEER REVIEW CRITERIA  

Applicants are encouraged to submit and describe their own ideas 
about how best to meet the goals of the RFA, and are expected to 
address issues identified under "SPECIAL REQUIREMENTS FOR THE 
RFA."  The peer review group will assess the merit of the 
applications and related factors as follows:  

Significance:  Does the proposed research project satisfy an 
important public health, occupational health, or infection control 
need?   Is the study population of appropriate size to address the 
question? Has the applicant attempted to address issues related to 
airway obstruction and/or susceptibility to infection?  Has the 
applicant proposed studies which integrate human responses with 
mechanistic studies at the molecular, cellular, and animal level?

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 approaches?  Is the worker 
cohort(s) adequate for the studies proposed?  Have confounding 
exposures been eliminated?   Does the applicant justify the 
proposed sample size and statistical power calculations?  Is the 
timetable for the proposed studies appropriate?  

Innovation:  Does the project employ novel concepts, approaches, 
or methods?  Is the project original and innovative?  Does the 
project develop new methodologies?   Does the project employ the 
latest molecular approaches to elucidate mechanisms?

Investigators:  Are the principal investigator and her/his 
collaborators appropriately trained and well-suited to carry out 
this work?  Do they have adequate experience in the areas of 
pulmonary medicine, particle analysis, molecular biology, cellular 
toxicology, epidemiology, and project management to carry out this 
work?  Is the work proposed appropriate to the experience level of 
the Principal Investigator and her/his collaborators? 

Environment:  Are the applicant=s facilities, equipment, and other 
resources adequate for the performance of this project?  Does the 
PI have the facilities necessary to monitor dust levels and 
measure dust components?

In addition to the above criteria, all applications will also be 
reviewed with respect to the following:

The reasonableness of the proposed budget and duration in relation 
to the proposed research.

The adequacy of plans to include both genders, minorities and 
their subgroups, and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated.

The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by 
the project proposed in the application.

AWARD CRITERIA

Applications recommended by the NIOSH Secondary Review Panel will 
be considered for award based upon (a) scientific and technical 
merit and (b) availability of funds.

SCHEDULE

Letter of Intent Receipt Date: March 28, 2000 
Application Receipt Date:      April 24, 2000 
Anticipated Award Date:        September 1, 2000  

INQUIRIES

Written and telephone inquiries concerning this RFA are 
encouraged.  The opportunity to clarify any issues or questions 
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Michael J. Galvin, Jr., Ph.D
Research Grants Program
Centers for Disease Control and Prevention (CDC)
1600 Clifton Road, NE
Building 1, Room 3065, MS D30
Atlanta, Georgia 30333
Email address: [email protected]

Direct inquiries regarding grants management matters to:

Sheryl L. Heard, Grants Management Specialist
Grants Management Branch, Procurement and Grants Office
Announcement 00052
Centers for Disease Control and Prevention (CDC)
2920 Brandywine Road, Mail Stop E-13
Atlanta, Georgia 30341
Telephone: (770) 488-2723
Email address: [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic 
Assistance No.93.262.  Awards are made under authorization of the 
Public Health Service Act, 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 42 CFR Parts 52 
and 45 CFR Part 74 [and Part 92 when applicable for State and 
Local governments].

LOBBYING RESTRICTIONS

Applicants should be aware of restrictions on the use of HHS funds 
for lobbying of Federal or State legislative bodies. Under the 
provisions of 31 U.S.C. Section 1352, recipients (and their sub-
tier contractors) are prohibited from using appropriated Federal 
funds (other than profits from a Federal contract) for lobbying 
congress or any Federal agency in connection with the award of a 
particular contract, grant, cooperative agreement, or loan. This 
includes grants/cooperative agreements that, in whole or in part, 
involve conferences for which Federal funds cannot be used 
directly or indirectly to encourage participants to lobby or to 
instruct participants on how to lobby.

In addition,  no part of CDC appropriated funds shall be used, 
other than for normal and recognized executive-legislative 
relationships, for publicity or propaganda purposes, for the 
preparation, distribution, or use of any kit, pamphlet, booklet, 
publication, radio, television, or video presentation designed to 
support or defeat legislation pending before the Congress or any 
State or local legislature, except in presentation to the Congress 
or any State or local legislature itself. No part of the 
appropriated funds shall be used to pay the salary or expenses of 
any grant or contract recipient, or agent acting for such 
recipient, related to any activity designed to influence 
legislation or appropriations pending before the Congress or any 
State or local legislature.

SMOKE-FREE WORKPLACE

The CDC strongly encourages all grant and contract recipients to 
provide a smoke-free workplace and promote the non-use of all 
tobacco products.  In addition, Public Law 103-227, the 
Pro-Children Act of 1994, prohibits smoking in certain facilities 
(or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is 
consistent with the CDC mission to protect and advance the 
physical and mental health of the American people.

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