Epidemiological evidence indicates an association between obesity and acute lung injury (ALI), but the molecular mechanisms mediating this association are poorly understood. Adiponectin is an adipose tissue-derived hormone that is present in high concentration in serum of humans and rodents and has well-documented anti-inflammatory and vascular protective properties in murine lung. Moreover, we recently demonstrated adiponectin to protect against development of LPS-induced ALI in mice and showed higher circulating levels are linked to increased mortality in patients with established acute respiratory failure of diverse etiologies. Together, these data support the notion that adiponectin plays an important role in lung homeostasis and disease. In this program, we will leverage existing clinical data and bio-specimens collected as part of the NIH ARDSNet Fluid and Catheter Treatment Trial in order to spearhead investigation into role of adiponectin in acute lung injury. This project will investigate the hypotheses that: 1) higher circulating levels f adiponectin in patients with ALI are linked to a more severe lung injury phenotype;and 2) higher plasma levels of adiponectin are associated with increased mortality. Overall, we believe these studies will establish adiponectin as a novel prognostic marker in ALI and will provide the foundation for future more mechanistic studies into the role of adiponectin in ALI.

Public Health Relevance

Acute lung injury is a syndrome that represents a major public health problem, affecting 200,000 people in the Unites States each year with a mortality rate of 30-40%. Recent evidence points to obesity as an important risk factor for development of ALI, but the molecular mechanisms mediating this association are unclear. Human and animal studies support a role for the adipose tissue-derived factor adiponectin in the pathogenesis of acute lung injury. Utilizing pre-existing data and stored biological specimens, this program will define associations between circulating levels of adiponectin and clinical outcomes in acute lung injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL112672-02
Application #
8466369
Study Section
Special Emphasis Panel (ZHL1-CSR-P (F2))
Program Officer
Wagner, Elizabeth
Project Start
2012-05-04
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$116,882
Indirect Cost
$45,482
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Walkey, Allan J; Demissie, Serkalem; Shah, Dilip et al. (2014) Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome. PLoS One 9:e108561
Stevenson, Elizabeth K; Rubenstein, Amanda R; Radin, Gregory T et al. (2014) Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*. Crit Care Med 42:625-31
Walkey, Allan J; Ambrus, Daniel; Benjamin, Emelia J (2013) The role of arrhythmias in defining cardiac dysfunction during sepsis. Am J Respir Crit Care Med 188:751
Walkey, Allan J; Wiener, Renda Soylemez (2013) Use of noninvasive ventilation in patients with acute respiratory failure, 2000-2009: a population-based study. Ann Am Thorac Soc 10:10-7