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Many scientists subscribe to the theory that novel viruses (like the 1918 pandemic, H5N1, and now novel H1N1) can unleash what is known as a `cytokine storm’ in some patients with a robust immune system.
Last February, in part 2 of my 3-part look at the Baskin Influenza Pathogenesis study I wrote this description of how we think a cytokine storm comes about.
Our innate immune system throws just about everything but the kitchen sink at an unrecognized infection.
In response our bodies spike a fever while natural killer cells and phagocytes rush to fight the infection. Our bodies produce protein and cytokine rich fluids at the site of the infection and cells throughout our body release inflammatory mediators.
Generally all of these things are good things, as they help fight the invading pathogen, although they are what make us so miserable when we have an infection.
Unfortunately, it is possible to have too much of a good thing.
On very rare occasions the body's innate immune system can overreact, go into overdrive, and overwhelm and damage the body's own organs - sometimes resulting in death.
This process is commonly called a `Cytokine Storm', although it is actually a poorly understood phenomenon, and not without controversy.
Cytokines, broadly speaking, are a category of signaling molecules that are used extensively in cellular communication.
They are often released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.
This `Cytokine Storm' has been described as a positive feedback loop, where immune cells - encountering a pathogen - secrete signaling cytokines which call more immune cells to the site of infection - which in turn secrete more cytokines - which call even more immune cells to join in the fight . . .
This cascade of immune cells rushing to the infection can, in rare instances, literally kill the patient. Their lungs can fill with fluid (which makes a terrific medium for a bacterial co-infection), and cells in the lungs (Type 1 & Type II Pneumocytes) can sustain severe damage.
Today, we’ve a press release in advance of the publication of a study to appear next month in American Thoracic Society's American Journal of Respiratory and Critical Care Medicine, that looks at the autopsy results of 21 pandemic flu victims.
Researchers found three separate types of severe lung damage, and point to signs of a cytokine storm response in some of these cases.
This from the American Thoracic Society.
Contact: Keely Savoie
ksavoie@thoracic.org
212-311-58620
American Thoracic Society
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 São 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 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, 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.
More pieces of the puzzle that will, in time, hopefully give us a better understanding how this novel virus, and perhaps other pandemic strains, affect their hosts.
For a better understanding of the pathogenesis of influenza, the innate immune system, and the role of cytokines I would invite you to read my 3-part look at the Baskin study.
Dissecting the Influenza Pathogenesis Study Pt. 1
