Older Men More Likely to Die from Pneumonia than
Women; Differing Response to Infection
Results suggest immune response to infection may be
important target to reduce sex disparities
April 29, 2009 - Old men are more likely do die
after being hospitalized with community-acquired pneumonia (CAP) than
are older women, according to new research that suggests the reason may
be differing biological response to infection between men and women.
Study of seniors finds physical activity, good
dietary habits, not smoking and light alcohol use lowers diabetes risk
by 82%; four in five new cases attributable to not having these low-risk
factors.
The findings, published online in the Critical
Care Medicine journal, may have important implications for
understanding sex differences in life expectancy, according to the
researchers.
"Our study found that men with CAP were less likely
to survive after an infection compared to women and this was not
explained by differences in demographics, health behavior, chronic
health conditions or quality of care," said Sachin Yende, M.D.,
assistant professor in the Department of Critical Care Medicine at the
University of Pittsburgh School of Medicine and corresponding author of
the study.
The researchers measured blood levels of
inflammatory indicators, coagulation indicators and fibrinolysis
indicators. 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 Dr. Yende.
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
● one 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 one year after the initial hospitalization,
when most patients had recovered from the pneumonia and left the
hospital."
"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 senior author Derek C. Angus, M.D., professor and
chair in the Department of Critical Care Medicine at the University of
Pittsburgh School of Medicine and principal investigator of the study.
"More studies will be needed to determine why the
biological response differs between men and women," said Dr. Yende.
"A clearer understanding may be useful toward
designing interventions specifically targeted to men or women."
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.
In a paper published online on April 3 in The
FASEB Journal, 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.
"Macrophage migration inhibitory factor is a
molecule that plays an important role in inflammation and has been shown
to worsen outcomes in animal models of sepsis. Our results are
intriguing in light of these findings and as other research groups are
trying to design human studies to block this molecule in sepsis," said
Dr. Yende. In future work, the researchers will continue to examine
relationships between sex and gene variations in CAP, sepsis and
survival.
Background by Information Source:
GenIMS is supported in part by the National
Institute of General Medical Science with additional support from
GlaxoSmithKline and Diagnostic Products Corporation. GenIMS was led by
several investigators in the Department of Critical Care Medicine and in
collaboration with other departments at the University of Pittsburgh,
including Emergency Medicine, Human Genetics and Biostatistics.
As one of the nation's leading academic centers
for biomedical research, the University of Pittsburgh School of Medicine
integrates advanced technology with basic science across a broad range
of disciplines in a continuous quest to harness the power of new
knowledge and improve the human condition.
Driven mainly by the School of Medicine and its
affiliates, Pitt has ranked among the top 10 recipients of funding from
the National Institutes of Health since 1997 and currently ranks fifth
in the nation, according to preliminary data for fiscal year 2008.
Likewise, the School of Medicine is equally committed to advancing the
quality and strength of its medical and graduate education programs, for
which it is recognized as an innovative leader, and to training highly
skilled, compassionate clinicians and creative scientists well-equipped
to engage in world-class research. The School of Medicine is the
academic partner of UPMC, which has collaborated with the University to
raise the standard of medical excellence in Pittsburgh and to position
health care as a driving force behind the region's economy. For more
information about the School of Medicine, see
www.medschool.pitt.edu.
Keep up with the latest news for senior citizens, baby
boomers
April 29, 2009 - Old men are more likely do die
after being hospitalized with community-acquired pneumonia (CAP) than
are older women, according to new research that suggests the reason may
be differing biological response to infection between men and women.