Researchers Find New
Patterns in H1N1 Deaths
researchers have performed the first-ever autopsy study to examine
the precise causes of death in victims of the H1N1 swine flu.
"The lack of information on the pathophysiology of this
novel disease is a limitation that prevents better clinical management
and hinders the development of a therapeutic strategy," said
lead author, Thais Mauad, M.D., Ph.D., associate professor of
the Department of Pathology at São Paulo University, in
The results of their study will be published in the January 1
issue of the American Thoracic Society's American Journal of Respiratory
and Critical Care Medicine.
The researchers examined 21 patients who had died in São
Paulo with confirmed H1N1 infection in July and August, 2009.
Most were between the ages of 30 and 59. They found that three-quarters
(76 percent) of the patients had underlying medical conditions
such as heart disease or cancer, and they all presented a progressive
and rapidly fatal form of the disease.
While previous data has shown that most patients with a non-fatal
infection have fever, cough and achiness (myalgia), Dr. Mauad
noted that "most patients with a fatal form of the disease
presented with difficulty breathing (dyspnea), with fever and
myalgia being less frequently present."
All patients died of severe acute lung injury, but there were
three distinct patterns of the damage to their lungs, indicating
that the infection killed in distinct ways. "All patients
have a picture of acute lung injury," said Dr. Mauad. "In
some patients this is the predominant pattern; in others, acute
lung injury is associated with necrotizing bronchiolitis (NB);
and in others there is a hemorrhagic pattern."
"Patients with NB are more likely to have a bacterial co-infection.
Patients with heart disease and cancer are more likely to have
a hemorrhagic condition in their lungs. It is important to bear
in mind that patients with underlying medical conditions must
be adequately monitored, since they are at greater risk of developing
a severe H1N1 infection," said Dr. Mauad. In these patients,
H1N1 infection may present as a potential fatal disease, requiring
early and prompt intensive care management, including protective
ventilation strategies and adequate hemodynamic management. "We
found that 38 percent of these patients had a bacterial infection
(bronchopneumonia). This has important consequences because these
patients need to receive antibiotic therapy, in addition to antiviral
The researchers also found evidence of an influenza-associated
"cytokine storm," an aberrant immune response in the
lungs of certain individuals, which was almost certainly involved
in the pathogenesis in these fatal cases of the H1N1 infection.
"[This] suggests that an overly vigorous host inflammatory
response triggered by the viral infection may spill over to and
damage lung tissue, thereby causing acute lung injury and fatal
respiratory failure," noted John Heffner, M.D., past president
of the ATS.
Further research is needed to understand precisely how and why
certain patients succumb to a fatal progression when infected
with H1N1. While most patients experience a mild illness with
no lasting effects, this research lays important groundwork for
future efforts by defining the histological patterns associated
with a fatal infection.
"We would like to deepen our efforts into the understanding
of the immune responses in cases of severe infection," said
Dr. Mauad. "This could ultimately lead to new therapeutic
Reference Sources 125
December 23, 2009