McGowan Institute for Regenerative Medicine
faculty member Derek Angus, MD (pictured), professor and chair in the Department of Critical Care Medicine at the University of Pittsburgh School of Medicine, was the principal investigator of the study which showed important implications for understanding sex differences in life expectancy. The findings indicated the differing biological response to infection between men and women which may explain higher death rates among older men who are hospitalized with community-acquired pneumonia (CAP).
“To our knowledge, this is the largest study comparing biological response to infection between men and women. Our results suggest that immune response to infection may be an important target for interventions to reduce sex disparities in the outcomes of infections,” said Dr. Angus.
The researchers measured blood levels of inflammatory indicators, including tumor necrosis factor (TNF) and interleukins 6 and 10, coagulation indicators including Factor IX, and fibrinolysis indicators including D-dimer concentrations. They found patterns in these biomarkers that suggest men generate a stronger inflammatory and coagulation response and, perhaps, break up blood clots more quickly than women in response to infection. “These differences in inflammatory, coagulation, and fibrinolysis biomarkers among men may explain the reduced short-term and long-term survival,” said Sachin Yende, MD, assistant professor in the Department of Critical Care Medicine at the University of Pittsburgh School of Medicine and corresponding author of the study.
Data were gathered from the multicenter Genetic and Inflammatory Markers of Sepsis (GenIMS) study. Participants were enrolled upon emergency department admission at 28 academic and community hospitals in Pennsylvania, Connecticut, Michigan, and Tennessee from 2001 to 2003. The study included 2,320 subjects, with a mean age of 64.9 years, 1,136 of whom were men. The men were sicker on admission, more likely to be smokers, and had at least one chronic health condition, such as cardiac disease or cancer. Severe sepsis occurred in 588 (31 percent) subjects. Of these, about half had severe sepsis on their first day of hospitalization.
Men had a higher risk than women of death at 30 days (7 percent vs. 4.5 percent), 90 days (11.4 percent vs. 8.6 percent), and 1 year (21 percent vs. 16 percent). “Even compared to women with an equivalent illness severity, men were more likely to die,” Dr. Yende noted. “Survival differences persist up to 1 year after the initial hospitalization, when most patients had recovered from the pneumonia and left the hospital.”
The GenIMS researchers hope to identify whether certain changes in the genes for key inflammatory molecules are associated with the risk of developing pneumonia, and the risk of progression to severe sepsis, septic shock, organ dysfunction, or death. Because pneumonia is the most common cause of sepsis, patients with this infection represent an excellent clinical model for studying sepsis in a relatively homogeneous population.
GenIMS researchers led by Drs. Yende and Angus found that people with certain gene variations associated with higher levels of macrophage migration inhibitory factor, an innate immune response regulator, were less likely to die following CAP.
In future work, the researchers will continue to examine relationships between sex and gene variations in CAP, sepsis, and survival.
Illustration: McGowan Institute for Regenerative Medicine.
University of Pittsburgh Schools of the Health Sciences Media Relations News Release (04/29/09)
Medical News Today (05/05/09)
Bio: Dr. Derek Angus
Abstract (Critical Care Medicine, 2009 May; 37(5):1655-62)
Abstract (The FASEB Journal, 2009 Apr 16. [Epub ahead of print])