[show abstract][hide abstract] ABSTRACT: In April 2010, a NIH workshop was convened to discuss the current state of understanding of lung cell plasticity, including the responses of epithelial cells to injury, with the objectives of summarizing what is known, what the field needs to know, and how to get there. The proximal stimulus for this workshop is the body of recent evidence suggesting that plasticity is a prominent but incompletely characterized property of lung epithelial cells, and that a focus on understanding this aspect of epithelial cell biology in particular, may be an important window into disease pathobiology and pathogenesis. In addition to their many vital functions in maintaining tissue homeostasis, epithelial cells have emerged as both a central target of disease initiation and an active contributor to disease progression, making a workshop to investigate the role of cell plasticity in lung injury and repair timely. The workshop was organized around four major themes: lung epithelial cell plasticity, signaling control of plasticity, fibroblast plasticity and crosstalk, and translation to human disease. Although this breakdown was recognized to be somewhat artificial, it was felt that this approach would promote cross-fertilization among groups that ordinarily do not communicate and lend itself to the generation of new approaches. The summary reports of individual group discussions below are followed by consensus priorities and recommendations of the workshop participants.
Proceedings of the American Thoracic Society 06/2011; 8(3):215-22.
[show abstract][hide abstract] ABSTRACT: The Division of Lung Diseases of the National Heart, Lung and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease (PVD); sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases, (2) injury, regeneration, and repair in the developing lung, (3) PVD in children, (4) development and adaptation of ventilatory responses to postnatal life, (5) nonatopic wheezing: aberrant large airway development or injury? (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases, and (7) predictive and personalized medicine for children.
[show abstract][hide abstract] ABSTRACT: Asthma is a heterogeneous disorder presenting with many phenotypes. Precise phenotypic definition has eluded the medical research community for years, despite recognition of different disease subtypes. Improved phenotypic characterization and knowledge of underlying pathobiology is necessary for linkage of specific genotypes with clinical disease manifestations.
Phenotyping has been difficult because asthma is likely to be comprised of overlapping syndromes with varying origins and heterogeneous pathobiology. Currently, the field is too reliant on classification by trigger or symptoms. Since genotypic and phenotypic heterogeneity are inherent in asthma, patients presenting with different asthma phenotypes may need tailored therapies. Studies have begun to link genetics with disease mechanism and therapeutic response. As disease etiology, onset, progression and severity vary greatly among patients, however, the relative contribution of genetic factors may be difficult to ascertain. Definition of the full array of complex biological consequences of molecular target modulation is a prerequisite for therapies based on this concept.
The advent of targeted therapies for asthma and clinical trials based on phenotype and genotype have raised interest in more accurate description of asthma phenotypes. Therapies based on phenotypic and genotypic characteristics may be useful in asthma management. A variety of factors, however, must be addressed before such approaches become standard.
Current opinion in pulmonary medicine 02/2007; 13(1):19-23. · 3.12 Impact Factor