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.

The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment.

RATIONALE: Pulmonary lymphangioleiomyomatosis is a progressive cystic lung disease that is associated with infiltration of atypical smooth muscle-like cells. Previous descriptions of clinical characteristics of subjects with lymphangioleiomyomatosis have been based on a limited number of patients. OBJECTIVES: To describe the clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms. METHODS: Over a 3-yr period, from 1998 to 2001, 243 subjects with pulmonary lymphangioleiomyomatosis were enrolled into a national registry; 13 subjects who had already undergone lung transplantation were excluded for the purposes of this report. MEASUREMENTS AND MAIN RESULTS: All 230 subjects were women, aged 18 to 76 yr (mean +/- SE, 44.5 +/- 0.65 yr). The average age at onset of symptoms was 38.9 +/- 0.73 yr and at diagnosis was 41.0 +/- 0.65 yr. Tuberous sclerosis complex was present in 14.8% of subjects. Pulmonary manifestations, most commonly spontaneous pneumothorax, were the primary events leading to the diagnosis in 86.5% of cases. Nearly 55% of the subjects were being treated with a progesterone derivative. An obstructive pattern on pulmonary function testing was observed in 57.3% of the subjects, whereas 33.9% had normal spirometric results. Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form. CONCLUSIONS: The age range of women afflicted with pulmonary lymphangioleiomyomatosis is broader than previously appreciated and the degree of pulmonary function can be quite variable, with one-third of subjects having normal spirometry at enrollment into this registry.

Progress and new directions in genetics of tuberculosis: an NHLBI working group report.

Tuberculosis (TB), along with AIDS and malaria, is one of the three major killers among infectious diseases. New approaches to preventing, diagnosing, and curing TB are needed, which depend on a better understanding of Mycobacterium tuberculosis and the host. The National Heart, Lung, and Blood Institute convened a working group to develop recommendations for future TB research, including genetic aspects of the disease. The following areas were identified: (1) animal model research to improve understanding of persistence, reactivation, and granulomatous reactions; (2) preclinical studies aimed at shortening treatment of TB; (3) new resources for manipulating and characterizing the M. tuberculosis genome, proteome chips for more specific diagnoses, and studies of genes that appear to be essential but whose functions are not known; (4) prospective studies associated with clinical trials in populations with or at risk of TB to advance development of diagnostics and prognostics; (5) new quantitative and bioinformatic approaches to study the interaction between M. tuberculosis and the infected host and how this influences the infection process; (6) molecular characterization of M. tuberculosis genome diversity and phylogenetic analysis; (7) coordinated studies of human genome scans; (8) genetic epidemiology studies; (9) activities to foster knowledge dissemination, education, and training; and (10) coordination between the National Institutes of Health, the Gates Foundation, the Global Alliance for Tuberculosis Drug Development, and other organizations.

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.