While there are some optimistic reports, the mortality for ARDS remains near 50%. Of the patients who die, one half survive beyond the first three days. In these patients who survive more than 3 days, signs of persistent lung and systemic inflammation are associated with increased mortality. Early autopsy series detected a large number of unsuspected cases of bacterial infection of the lung in persons dying with ARDS. In more recent clinical studies culture of bronchoscopic samples from live patients without clinical signs of pneumonia have not yielded a high prevalence of results that meet strict criteria for pneumonia. However, a large fraction of samples did contain bacteria and the prevalence of samples with bacteria increased with time on the ventilator. In addition to bacterial colonization of the lung itself, translocation of bacteria across the intestinal wall occurs in severely ill patients, and especially those with shock. The use of broad spectrum antibiotics in patients with ARDS limits the sensitivity of strict quantitative culture criteria to accurately quantify the bacterial burden in ARDS patients. We hypothesize that a significant portion of the persistent acute inflammation present in the lungs of ARDS patients derives from bacteria which colonize the lung surfaces and/or translocate into the blood stream. In the case of bacteria which translocate into the blood stream the primed lung becomes the subject of a response similar to the Shwartzman phenomenon. Recent studies have not detected high levels of lung colonization or blood stream invasion by bacteria because of the ubiquitous use of broad spectrum antibiotics. We will measure bacterial burden in the lung and blood stream of ARDS patients using PCR for bacterial DNA, the sensitivity of which is not as limited by the presence of antibiotics. We will determine if the bacterial burden in the lung and blood as an independent predictor of mortality and if it correlates with indices of acute inflammation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
1P50HL060316-01
Application #
6110988
Study Section
Project Start
1998-09-30
Project End
1999-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Nyunoya, Toru; Monick, Martha M; Klingelhutz, Aloysius L et al. (2009) Cigarette smoke induces cellular senescence via Werner's syndrome protein down-regulation. Am J Respir Crit Care Med 179:279-87
Monick, Martha M; Powers, Linda S; Barrett, Christopher W et al. (2008) Constitutive ERK MAPK activity regulates macrophage ATP production and mitochondrial integrity. J Immunol 180:7485-96
Hansdottir, Sif; Monick, Martha M; Hinde, Sara L et al. (2008) Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 181:7090-9
Groskreutz, Dayna J; Monick, Martha M; Yarovinsky, Timur O et al. (2007) Respiratory syncytial virus decreases p53 protein to prolong survival of airway epithelial cells. J Immunol 179:2741-7
Monick, Martha M; Powers, Linda S; Hassan, Ihab et al. (2007) Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC/CCL17. J Immunol 179:1648-58
Ashare, Alix; Monick, Martha M; Nymon, Amanda B et al. (2007) Pseudomonas aeruginosa delays Kupffer cell death via stabilization of the X-chromosome-linked inhibitor of apoptosis protein. J Immunol 179:505-13
Monick, Martha M; Powers, Linda S; Gross, Thomas J et al. (2006) Active ERK contributes to protein translation by preventing JNK-dependent inhibition of protein phosphatase 1. J Immunol 177:1636-45
Flaherty, Dawn M; Monick, Martha M; Hinde, Sara L (2006) Human alveolar macrophages are deficient in PTEN. The role of endogenous oxidants. J Biol Chem 281:5058-64
Groskreutz, Dayna J; Monick, Martha M; Powers, Linda S et al. (2006) Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. J Immunol 176:1733-40
Nyunoya, Toru; Monick, Martha M; Klingelhutz, Aloysius et al. (2006) Cigarette smoke induces cellular senescence. Am J Respir Cell Mol Biol 35:681-8

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