The goal of this proposal is to seek continued support to augment and sustain an established Alcohol Research Resource, known as CoPARC (Colorado Pulmonary-Alcohol Research Collaborative). CoPARC's mission is to facilitate research that will prevent the development of alcohol-associated pneumonia, ameliorate its deleterious complications, and ultimately improve clinical outcomes. Alcohol use disorders (AUDs) confer an eight-fold increased risk for community-acquired pneumonia. AUDs also increase morbidity for patients with pneumonia, including increasing the risk of respiratory failure necessitating intensive care unit (ICU) admission and mechanical ventilation. Further, AUD-associated pneumonia is frequently complicated by the development of the acute respiratory distress syndrome (ARDS). Centered at the University of Colorado Denver (UCD) and led by Ellen L. Burnham, MD, MS, the CoPARC infrastructure has enabled enrollment of over 370 ambulatory subjects with and without AUDs, and 237 critically ill patients with pneumonia or burn injury, established ARDS risk factors that are more prevalent in patients with AUDs. Resource materials have originated from institutions with a history of NIAAA-funded translational research in alcohol-related pulmonary diseases, including UCD, Emory University (EU), and Loyola University Chicago (LUC); and from the University of California San Francisco (UCSF) with NHLBI support. Presently, thousands of biospecimens have been collected, including bronchoalveolar lavage (BAL) fluid and cell aliquots; bronchial brushings; and blood specimens. To date, 26 investigators from 11 external institutions have utilized over 6100 biospecimens from 92% of the enrolled subjects. For the renewal, 4 sites (EU, LUC, UCSF, and the University of Nebraska Medical Center) and UCD will collect materials for CoPARC. A Steering Committee comprised of investigators from UCD, EU, LUC, Louisiana State University, UNMC, and Thomas Jefferson University will provide rigorous oversight for CoPARC, including prioritization of biospecimen distribution, and ensuring that milestones promoting use of the Resource are achieved. Innovations that are planned include collection of novel specimens such as whole lung explants; expertise in high-throughput genomics applications; access to administrative data sets enriched in patients with alcohol use; and organization of clinical, inventory, and experimental data to foster cross- investigator sharing.
Aims for the renewal are in line with the NIAAA's strategic plan to identify mechanisms of alcohol action and alcohol-related pathology to more fully understand how alcohol asserts its effects on human health. They include: 1) expand and diversify clinical and biological materials obtained from ambulatory subjects with AUDs and critically ill patients, along with appropriate controls, 2) engage emerging web-based systems to prioritize data and biospecimen sharing, and streamline communications between investigators as well as the Steering Committee and 3) enhance visibility and marketing to promote the distribution, growth, and sustainability of the Resource.
Alcohol use disorders (AUDs) substantially increase the risk of developing pneumonia. In people with AUDs, pneumonia is more severe, mortality is higher, and patients are more likely to develop respiratory failure and the acute respiratory distress syndrome. Understanding the effects of AUDs on the pulmonary immune system can help to develop new strategies to treat patients with pneumonia that will improve health outcomes and decrease the economic burden of this disease.
|Samuelson, Derrick R; Burnham, Ellen L; Maffei, Vincent J et al. (2018) The respiratory tract microbial biogeography in alcohol use disorder. Am J Physiol Lung Cell Mol Physiol 314:L107-L117|
|Afshar, Majid; Burnham, Ellen L; Joyce, Cara et al. (2018) Injury Characteristics and von Willebrand Factor for the Prediction of Acute Respiratory Distress Syndrome in Patients With Burn Injury: Development and Internal Validation. Ann Surg :|
|Frankel, John H; Boe, Devin M; Albright, Joslyn M et al. (2018) Age-related immune responses after burn and inhalation injury are associated with altered clinical outcomes. Exp Gerontol 105:78-86|
|Afshar, Majid; Burnham, Ellen L; Joyce, Cara et al. (2018) Optimal Cut-Points for Phosphatidylethanol Vary by Clinical Setting: Response to Nguyen and Seth's (2018) Letter to the Editor. Alcohol Clin Exp Res 42:2064-2065|
|Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela et al. (2018) Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 66:35-43|
|Maffei, Vincent J; Kim, Sangkyu; Blanchard 4th, Eugene et al. (2017) Biological Aging and the Human Gut Microbiota. J Gerontol A Biol Sci Med Sci 72:1474-1482|
|Fini, Mehdi A; Gaydos, Jeanette; McNally, Alicia et al. (2017) Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity. Am J Physiol Lung Cell Mol Physiol 313:L1047-L1057|
|Aschner, Yael; Burnham, Ellen L (2017) Adjuvant Therapies for ARDS: Not Ready for Prime Time? Ann Am Thorac Soc 14:14-16|
|Sapkota, Muna; Burnham, Ellen L; DeVasure, Jane M et al. (2017) Malondialdehyde-Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies. Alcohol Clin Exp Res 41:2093-2099|
|Nedumaran, Balachandar; Rudra, Pratyaydipta; Gaydos, Jeanette et al. (2017) Impact of Regular Cannabis Use on Biomarkers of Lower Urinary Tract Function. Urology 109:223.e9-223.e16|
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