National Heart, Lung, and Blood Institute perspective: lung progenitor and stem cells--gaps in knowledge and future opportunities.

Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung. Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung. While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

NHLBI workshop: respiratory medicine-related research training for adult and pediatric fellows.

The pulmonary physician-scientist has a special niche to generate basic research findings and apply them to a clinical disease and perhaps impact its medical care. The availability of new high throughput-based scientific technologies in the "omics era" has made this an opportune time for physician scientists to prepare and embark on an academic career in respiratory disease research. However, maintaining an adequate flow through the research pipeline of physician-scientist investigators studying respiratory system diseases is currently a challenge. There may not be a sufficient workforce emerging to capitalize on current research opportunities. The National Heart, Lung, and Blood Institute (NHLBI) organized a workshop to assess ways to attract and properly train advanced fellows to pursue research careers in adult and pediatric lung diseases. Participants included representatives from the various pulmonary training programs, respiratory-related professional societies, and NHLBI staff. Deliberation centered on present barriers that might affect interest in pursuing research training, devising better incentives to attract more trainees, and how current research support offered by the NHLBI and the Professional Societies (in partnership with Industry and Patient Support groups) might be better coordinated and optimized to ensure a continued pipeline of pulmonary investigators. Major recommendations offered are: (1) Attract trainees to pulmonary/critical care medicine-based research careers by increasing research exposure and opportunities for high school, college, and medical students. (2) Increase awareness of the outstanding physician-scientist role models in the lung community for trainees. (3) Facilitate mechanisms by which the lung community (NHLBI, professional societies, and partners) can better support and bridge senior fellows as they transition from Institutional Training Grants (T32) to Career Series (K) awards in their early faculty career development.

Past achievements and future directions of sarcoidosis research: a NHLBI perspective.

This history of research on sarcoidosis is largely from the perspective of the National Heart, Lung, and Blood Institute of the National Insititutes of Health which has had an interest in this disease since the inception of the Lung Program in 1969. BACKGROUND: Cutaneous sarcoidosis was described over 130 years ago and, subsequently, many reports have documented this illness affecting many organs or body sites. But a definitive cause has remained elusive. Multiple research stimuli converged in the early 1970s to begin an era of active investigation into the immunopathogensis of this granulomatous disease that included: new insights into host cellular immunity and lymphocytes; program analysis of lung research in 1971-72; new technology, especially the fiberoptic bronchoscope; and a focus by the NIH Intramural Pulmonary Branch to conduct research on interstitial lung diseases begun in 1974. During the mid 1970-80s, research into lung cellular immunity of sarcoidosis patients developed rapidly at NIH and at many other centers across the US, England, Europe, and Asia. PRESENT AND FUTURE DIRECTIONS: NHLBI has continued active support of research in sarcoidosis, both basic and clinical, such as the A Case Control Etiologic Study of Sarcoidosis (ACCESS) program, 1995-2003, whose conclusions are continuing to be published. A workshop on "Future Directions in Sarcoidosis Research" provided new research ideas to explore basic immunity mechanisms in human sarcoidosis tissue and search for latent microbial agents in tissue. The organization of sarcoidosis patient support groups has heightened awareness of the need for research on multiple organs affected by the disease in addition to the respiratory tract. In response, a trans-NIH sarcoidosis working group has been formed to assess this need and to better coordinate NIH research efforts.

Interstitial lung diseases--where we started from and are now going.

BACKGROUND AND AIM: Research into mechanisms causing interstitial lung diseases (ILD) began 35 years ago with the advent of cellular immunology and techniques to sample airways for biologic materials. After an analysis of lung research programs by the then National Heart and Lung Institute in 1972 identified as a priority the study of fibrotic and immunologic lung diseases, this began in the Pulmonary Branch (1974) of the Institute's intramural program. The Division of Lung Diseases initiated extramural research support also. ILD research developed quickly at many centers in the US and throughout the world. This review focuses on idiopathic pulmonary fibrosis (IPF) and highlights some of the initial research from the Pulmonary Branch. RECENT RESEARCH PARADIGM: In the 1990s research emphasis changed from a focus on inflammation to alveolar epithelial injury, fibrogenesis in fibroblastic foci, myofibroblast function, cytokine secretion and disordered matrix remodeling. More precise classification of ILD was advocated, especially for IPF. New strategies for therapy of IPF followed, including anti-fibrotic agents and interferon gamma treatment. However, therapy is still not sufficiently effective. Much is still left to do. FUTURE DIRECTIONS: The NHLBI research support continues for ILD, especially IPF. Current programs include: searching for new molecular therapeutic targets; establishing of a clinical network for IPF patients to assess combinations of therapy and new agents as appropriate; identifying genomic and genetic susceptibility factors; and creating a repository for lung tissue and biologic samples to aid investigators.

The pipeline: preparing and training pulmonary scientists for research careers.

New technologies have made this an opportune time to prepare and embark on an academic career in respiratory disease research. The pulmonary physician-scientist has a special advantage to take basic research findings to the patient's illness and impact medical care. But is there a sufficient work force emerging to capitalize on current research opportunities? The aim of this study was to analyze the present workforce of potential clinical investigators available by reviewing the mechanisms of training support as provided by the National Heart Lung and Blood Institute (NHLBI) and by the professional pulmonary societies, including their patient advocacy groups and pharmaceutical partners, and by discussing how support for research training might be improved for advanced clinical fellows. Of the approximately 500 fellows/year in a final training year in Pulmonary/Critical Care Medicine and related programs, about one third are involved mainly in supervised research and of whom about two thirds plan to continue fellowship training for an additional year or more (approximately 100-120 trainees). It seems especially important to encourage his particular group who are planning to extend fellowship for research training. Both the NHLBI and the professional pulmonary societies and their partners provide support for advanced fellowship trainees, but resources are limited. To insure that enough well-trained new clinical investigators will be available to conduct future pulmonary research, funding support and other career inducements should be discussed collectively by the NHLBI and the professional pulmonary societies for the purpose of optimizing support for advanced fellowship trainees.

Future directions in sarcoidosis research: summary of an NHLBI working group.

Sarcoidosis is a systemic granulomatous disease of unknown etiology that primarily affects the lungs. The etiology remains unclear; however, environmental, genetic, ethnic, and familial factors probably modify expression of the disease. As an example, African Americans are at greater risk of mortality and morbidity than are white Americans, and more often have a family history of sarcoidosis. Most patients with sarcoidosis recover spontaneously, but some develop chronic, debilitating disease. Corticosteroids and other drugs, although effective at controlling disease activity, may not influence the overall course of disease. Because of the many uncertainties about the pathogenesis, course, and management of sarcoidosis, the National Heart, Lung, and Blood Institute convened a working group to identify future research directions and opportunities for sarcoidosis. These include developing a tissue bank, using novel methods to identify genetic factors, studying the immunopathogenesis with human tissue and animal models, exploring new approaches to diagnose and manage disease, and, finally, conducting randomized controlled trials to assess new therapies.

Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group.

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose. Although mortality from ALI/ARDS has decreased in the last decade, it remains high. Despite two major advances in treatment, low VT ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause of ALI/ARDS), additional research is needed to develop specific treatments and improve understanding of the pathogenesis of these syndromes. The NHLBI convened a working group to develop specific recommendations for future ALI/ARDS research. Improved understanding of disease heterogeneity through use of evolving biologic, genomic, and genetic approaches should provide major new insights into pathogenesis of ALI. Cellular and molecular methods combined with animal and clinical studies should lead to further progress in the detection and treatment of this complex disease.