Researchers find new patterns in H1N1 deaths

[Ronan Kelly]

Researchers find new patterns in H1N1 deaths
Brazilian 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 S?o Paulo University, in Brazil.

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 S?o 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, but there was no clear complicating medical condition in the remaining quarter. 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 therapy."

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 approaches."


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http://www.eurekalert.org/pub_releases/2009-12/ats-rfn121609.php

 

[Ronan Kelly]

Re: Researchers find new patterns in H1N1 deaths

Autopsies Reveal Three Patterns of H1N1 Death
By Michael Smith, North American Correspondent, MedPage Today
Published: December 23, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco. Earn CME/CE credit
for reading medical news


Brazilian researchers have found three distinct patterns of lung damage in patients who died of the H1N1 pandemic flu.

They also found evidence of a so-called "cytokine storm," a runaway immune response associated with the lung damage, according to Thais Mauad, MD, PhD, of Sao Paulo University Medical School, and colleagues.
The findings come from the first autopsy series of patients who succumbed to the pandemic influenza strain, Mauad and colleagues wrote in the Jan. 1 issue of the American Journal of Respiratory and Critical Care Medicine.

The researchers reported on autopsies of 21 patients performed during July and August of 2009, the winter flu season in the Southern Hemisphere.
Action Points
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■Note that this series of autopsies found three distinct patterns of lung damage in patients who died of H1N1 flu.


■Be aware that while most patients with the H1N1 strain do not have shortness of breath, it was a common symptom among those patients whose infection was fatal.


Most patients with an H1N1 infection have standard flu-like symptoms that include fever, cough, and myalgia and a "benign course," the researchers said.

But 86% of the patients in this series presented with shortness of breath, as well as cough, fever, and muscle aches, they found.

In addition, they said, 16 of the 21 had preexisting medical conditions, including chronic cardiovascular diseases and cancer. Relatively few had chronic respiratory disease, diabetes, or obesity -- about 10% for all conditions.

All patients had respiratory failure and needed mechanical ventilation, while 15 had acute respiratory distress syndrome (ARDS). The remaining six had acute lung damage that did not meet all the criteria for ARDS, the researchers reported.

But not all cases of lung damage were the same:

?Nine patients had classic exudative diffuse alveolar damage (DAD), characterized by alveolar and interstitial edema, alveolar fibrinous exudate with hyaline membranes, and reactive pneumocytes.
?Six patients had DAD along with severe necrotizing bronchiolitis, characterized by extensive necrosis of the bronchiolar wall and a bronchiolar lumen densely infiltrated by neutrophils.
?And five patients had exudative DAD with an intense hemorrhagic component.
?The remaining patient had no interstitial changes induced by the virus. Death in that case -- a patient with laryngeal cancer -- was caused by pulmonary thromboembolism and bacterial pneumonia.

A large fraction of the patients (38%) had evidence of bacterial coinfection, the researchers found, suggesting that antibiotic therapy might have clinical value.

In addition, there were high circulating levels of toll-like receptor-3 and interferon-gamma, as well as a large number of CD8-positive T cells and granzyme B-positive cells in the lung tissue.

The researchers said in the journal that the results imply that "viral overload leads to altered innate immune responses" that lead to inflammation in the lung tissue.

Indeed, the study "suggests that an overly vigorous host inflammatory response triggered by the viral infection may spill over to and damage lung tissue," according to John Heffner, MD, of Providence Health and Services in Portland, Ore.

That process could lead to "acute lung injury and fatal respiratory failure," Heffner said in a statement. Heffner, a former president of the American Thoracic Society, was not part of the research team.

The researchers did not report any external support for the study or any financial conflicts.


Primary source: American Journal of Respiratory and Critical Care Medicine
Source reference:
Mauad T, et al "Lung pathology in fatal novel human influenza A (H1N1) infection" Am J Respir Crit Care Med 2010; 181: 1?8.

http://www.eurekalert.org/pub_releases/2009-12/ats-rfn121609.php