Researchers in Brazil who carried out the first autopsy study of victims who died of H1N1 swine flu to establish the precise causes of death, have discovered some new patterns of the disease.

Their research appears as a paper in the 1 January 2010 print issue of the American Journal of Respiratory and Critical Care Medicine.

Lead author, Dr Thais Mauad, associate professor of the Department of Pathology at São Paulo University, told the media why we need to understand more about the novel H1N1 swine flu virus:

“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.”

For the study, Mauad and colleagues examined the bodies of 21 patients mostly aged between 30 and 59 when they died in São Paulo with confirmed H1N1 infection during July and August 2009.

All the patients had presented a progressive and rapidly fatal form of the disease: 76 per cent of the patients had underlying medical conditions such as cancer or heart disease, but the others had no clear complicating medical condition.

Mauad explained that while research shows that most patients with a non-fatal infection of H1N1 swine flu have fever, cough and achiness (myalgia):

“Most patients with a fatal form of the disease presented with difficulty breathing (dyspnea), with fever and myalgia being less frequently present.”

He said they found that all the patients had died of severe acute lung injury, but there appeared to be three distinctly different patterns of damage to the lungs. In some patients the prodominant pattern was acute lung injury, but in the others they found this was either associated with “necrotizing bronchiolitis (NB)” or with a “hemorrhagic pattern”.

Mauad explained that patients with NB were more likely to have a bacterial co-infection, while patients with heart disease and cancer were 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 Mauad, adding that in these patients, H1N1 swine flu is potentially fatal, and they need early and prompt intensive care, protective ventilation 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,” said Mauad.

The researchers also found that some patients showed traces of a “cytokine storm”, where their immune systems had over-reacted, causing an inflammatory response that spilled over and damaged lung tissue, which led to the acute lung injury and fatal respiratory failure.

They said further studies should now be done to find out exactly why some patients infected with H1N1 progress and succumb rapidly to a fatal form of the disease, while most people only have mild symptoms with no lasting effects.

“We would like to deepen our efforts into the understanding of the immune responses in cases of severe infection,” said Mauad, explaining that such an understanding would help develop new therapies for such patients.

“Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection.”
Thais Mauad, Ludhmila A. Hajjar, Giovanna D. Callegari, Luiz F. F. da Silva, Denise Schout, Filomena R. B. G. Galas, Venancio A. F. Alves, Denise M. A. C. Malheiros, Jose O. C. Auler, Jr., Aurea F. Ferreira, Marcela R. L. Borsato, Stephania M. Bezerra, Paulo S. Gutierrez, Elia T. E. G. Caldini, Carlos A. Pasqualucci, Marisa Dolhnikoff, and Paulo H. N. Saldiva.
Am J Respir Crit Care Med, Jan 2010; 181: 72 – 7
DOI:10.1164/rccm.200909-1420OC

Source: American Thoracic Society.

Written by: Catharine Paddock, PhD