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1.  Malfolded Protein Structure and Proteostasis in Lung Diseases 
Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on “Malformed Protein Structure and Proteostasis in Lung Diseases” was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment.
doi:10.1164/rccm.201306-1164WS
PMCID: PMC3919126  PMID: 24033344
protein misfolding; post-translational processing; proteosome; ubiquitination; pulmonary health
3.  Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research 
Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI.
doi:10.1093/jnci/djp023
PMCID: PMC2669099  PMID: 19351920
5.  Long-term Oxygen Treatment in Chronic Obstructive Pulmonary Disease: Recommendations for Future Research 
Long-term oxygen treatment (LTOT) prolongs life in patients with chronic obstructive pulmonary disease (COPD) and severe resting hypoxemia. Although this benefit is proven by clinical trials, scientific research has not provided definitive guidance regarding who should receive LTOT and how it should be delivered. Deficiencies in knowledge and in current research activity related to LTOT are especially striking in comparison to the importance of LTOT in the management of COPD and the associated costs. The National Heart, Lung, and Blood Institute, in collaboration with the Centers for Medicare and Medicaid Services, convened a working group to discuss research on LTOT. Participants in this meeting identified specific areas in which further investigation would likely lead to improvements in the care of patients with COPD or reductions in the cost of their care. The group recommended four clinical trials in subjects with COPD: (1) efficacy of ambulatory O2 supplementation in subjects who experience oxyhemoglobin desaturation during physical activity but are not severely hypoxemic at rest; (2) efficacy of LTOT in subjects with severe COPD and only moderate hypoxemia; (3) efficacy of nocturnal O2 supplementation in subjects who show episodic desaturation during sleep that is not attributable to obstructive sleep apnea; and (4) effectiveness of an activity-dependent prescription for O2 flow rate that is based on clinical tests performed at rest, during exercise, and during sleep.
doi:10.1164/rccm.200507-1161WS
PMCID: PMC2648117  PMID: 16614349
chronic bronchitis; hypoxia, therapy; lung diseases, obstructive; oxygen inhalation therapy; pulmonary emphysema

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