PROJECT 3:This project will elucidate basic mechanisms linking sleep disordered breathing with accelerated decline inpulmonary and systemic manifestations of COPD. Its overall hypothesis is that sleep disorderedbreathing in COPD triggers pulmonary and systemic inflammatory responses, which can bemitigated by a novel therapeutic strategy. A combination of human and murine models will be utilized toaddress this hypothesis. Human studies are designed to elucidate unique physiologic mechanisms of sleepdisordered breathing in COPD, characterize its impact on nocturnal oxygenation and systemic inflammation,and pilot novel therapy to prevent accelerated decline in COPD. These human studies will derive crucialsupport from parallel SCCOR studies of inflammatory profiles and therapeutic trials in COPD patients. Incomplementary murine studies, this project will model the effects of intermittent hypoxemia in sleepdisordered breathing, and in concert with basic lung biologists involved in this SCCOR program, will dissectfundamental molecular antimorphogenic and proinflammatory mechanisms of COPD progression. Ourproposal has immediate clinical implications for the patient with COPD. It will provide new non-invasivephysiologic and serum markers of disease progression. These markers may be used to stratify COPDpatients at increased risk of morbidity and mortality, target particular patient subgroups for early intervention,and monitor therapeutic responses. This project will provide fundamental molecular, physiologic andtherapeutic insights from a unique combination of human and murine studies, which will ultimately improvehealth outcomes in COPD.
| Robert, H Brown; Robert, A Wise; Kirk, Gregory et al. (2015) Lung density changes with growth and inflation. Chest 148:995-1002 |
| Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C et al. (2014) Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia. J Appl Physiol (1985) 117:765-76 |
| Sussan, Thomas E; Ingole, Vijendra; Kim, Jung-Hyun et al. (2014) Source of biomass cooking fuel determines pulmonary response to household air pollution. Am J Respir Cell Mol Biol 50:538-48 |
| McGrath-Morrow, Sharon A; Lauer, Thomas; Collaco, Joseph M et al. (2014) Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status. Cytokine 65:4-9 |
| Mundel, Toby; Feng, Sheng; Tatkov, Stanislav et al. (2013) Mechanisms of nasal high flow on ventilation during wakefulness and sleep. J Appl Physiol (1985) 114:1058-65 |
| Yao, Qiaoling; Shin, Mi-Kyung; Jun, Jonathan C et al. (2013) Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues. J Lipid Res 54:1058-65 |
| Aggarwal, Neil R; D'Alessio, Franco R; Eto, Yoshiki et al. (2013) Macrophage A2A adenosinergic receptor modulates oxygen-induced augmentation of murine lung injury. Am J Respir Cell Mol Biol 48:635-46 |
| Putcha, Nirupama; Puhan, Milo A; Hansel, Nadia N et al. (2013) Impact of co-morbidities on self-rated health in self-reported COPD: an analysis of NHANES 2001-2008. COPD 10:324-32 |
| Nilius, Georg; Franke, Karl-Josef; Domanski, Ulrike et al. (2013) Effects of nasal insufflation on arterial gas exchange and breathing pattern in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure. Adv Exp Med Biol 755:27-34 |
| Lockett, Angelia D; Kimani, Samuel; Ddungu, Godfrey et al. (2013) ??-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-?. Am J Respir Cell Mol Biol 49:143-50 |
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