DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NHLBI SPECIAL EMPHASIS PANEL
ON STRATEGIES TO AUGMENT ALVEOLARIZATION

MINUTES OF MEETING 
SEPTEMBER 29, 1997

The meeting of the Special Emphasis Panel on Strategies to
Augment Alveolarization was convened at 9:00 A.M. at the Division
of Lung Diseases Conference Room 10029, 6701 Rockledge Drive,
Bethesda, MD. In accordance with Public law 92-463, the entire
meeting was open to the public.

OPEN MEETING

I.   Call to Order

The meeting was called to order by Dr. Merton Bernfield.  Dr.
Berberich presented the charge to the Panel:  


The Panel was charged with the following tasks:

1.   to identify gaps in our knowledge of the process of          
     alveolarization  

2.   to clarify the science of retinoic acid (RA) action in the   
     lung

3.   to uncover barriers to clinical application

4.   to advise NHLBI on best way to stimulate research into this  
     exciting and important area

II. Review of Confidentiality and Conflict of Interest Procedures 

Dr. Berberich informed the Panel members about the requirement to
read and sign the conflict of interest statement.  All panel
members signed the requisite forms.

III. Discussion of Proposed Concept Areas

The panel's expertise represented the areas of morphogenesis,
differentiation, RA metabolism and clinical experience in RA
metabolism and chronic lung disease.  Brief presentations were
made on the following topics relevant to alveolarization: 
Alveolarization in the Developing Lung; Alveolar Regeneration in
the Adult Lung; Role of RA in Limb Development; Administration of
Retinols to Premature Babies with Vitamin A Deficiency. 
Extensive discussion identified areas where additional
information is required to better understand alveolarization in
the developing and adult lung, in order to assess the
opportunities for pharmacological augmentation of
alveolarization:

1.   Stem cells and markers for septal formation in               
     alveolarization

2.   Genes induced by RA for insight into whether remodeling and  
     development utilize the same pathways

3.   Activity of other retinoid analogues, agonists, and          
     antagonists on alveolarization

4.   Lipid-laden lung fibroblast population in presence and       
     absence of RA 

5.   RA receptors in emphysema model

6.   Characteristics of emphysema in elastase rat models and in   
     adult human smokers

7.   Reversibility of RA effect on increased septation

8    Function of newly formed alveoli

9.   RA use in prevention as well as repair

10.  Other animal models representative of emphysema

11.  Tissue levels of RA in premature infants and in adults

12.  Dose and pharmacology of RA for potential clinical use

13.  Toxicity assessment

14.  Quantification of emphysema by CT scan etc.

15.  Epidemiology and availability of material from other studies

16.  Appropriate measure of outcome for clinical application

Recognizing the potential clinical importance of RA
administration on alveolarization, NHLBI requested the Special
Emphasis Panel (SEP) to determine whether the appropriate steps
are being taken to ensure maximal benefit from this emerging
area.  The discussants acknowledged that since 1992 NHLBI has
invested, and continues to invest, in a broad array of both
investigator- and institute-initiated projects, directed toward
an understanding of the molecular embryology of the lung.  The
goal of these studies is to unravel the complexity of the
integrated network of factors involved in lung development and to
apply this knowledge to the development of rational clinical
interventions to ensure normal development and to alter disease
processes.  The effect of RA on alveolarization in both the
developing and adult lung suggests that developmental processes
may be relevant to repair of the lung following injury.  The SEP
consensus was that investigations into the above list of topics,
in conjunction with the ongoing emphasis on molecular
organogenesis and differentiation, would generate important
findings into regulation, control, and augmentation of
alveolarization in both developing and adult lung.
.