Am J Respir Crit Care Med. Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection

[Francoise Ramona]

H1N1: une forme "rapidement fatale" de la maladie ? l'origine des d?c?s

WASHINGTON - Les personnes d?c?d?es de la grippe H1N1 ont contract? une forme "rapidement fatale" de la maladie mais qui tue de diff?rentes mani?res, selon une ?tude publi?e jeudi aux Etats-Unis.
Des chercheurs ont ?tudi? les cas de 21 patients ?g?s de 1 ? 68 ans, d?c?d?s en juillet et ao?t ? Sao Paulo, au Br?sil, des suites de la grippe H1N1.
L'ensemble de ces 21 patients "pr?sentait une forme progressive et rapidement fatale de la maladie", selon cette ?tude ? para?tre dans l'?dition du 1er janvier de l'American journal of Respiratory and Critical Care Medicine, le journal de la soci?t? am?ricaine des maladies du thorax (American Thoracic Society).
Tous ces patients sont morts de l?sions s?v?res des poumons, mais ces l?sions ?taient de trois types diff?rents, selon l'?tude, qui conclut donc que la grippe H1N1 "tue de diff?rentes mani?res".
Certains patients d?c?d?s avaient seulement des l?sions des poumons s?v?res, mais chez d'autres elles ?taient associ?es ? une bronchiolite (inflammation des petites bronches) et chez d'autres encore ? une "tendance h?morragique", explique Tha?s Mauad, professeur associ?e au d?partement de Pathologie de l'universit? de Sao Paulo et principal auteur de l'?tude.
"Il est important d'avoir ? l'esprit le fait que les patients ayant des probl?mes de sant? pr?alables doivent ?tre correctement surveill?s car ils pr?sentent un risque accru d'infection s?v?re par le H1N1", souligne Thais Mauad.
Seize des 21 patients ?tudi?s par son ?quipe souffraient de probl?mes de sant? chroniques, comme des maladies de coeur ou des cancers.
Les chercheurs ont aussi d?couvert une "r?ponse immunitaire aberrante" chez certains patients, ce qui "laisse penser qu'une r?ponse inflammatoire exag?r?e entra?n?e par l'infection virale a pu d?g?n?rer et endommager les tissus pulmonaires, provoquant des l?sions s?v?res des poumons et une insuffisance respiratoire fatale", explique John Heffner, de l'American Thoracic Society.
(?AFP / 24 d?cembre 2009 21h15)

[SIZE=+1]Published ahead of print on October 29, 2009, doi:10.1164/rccm.200909-1420OC[/SIZE]

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</td></tr> </tbody></table> </td></tr></tbody></table> [SIZE=-1] American Journal of Respiratory and Critical Care Medicine Vol 181. pp. 72-79, (2010)
? 2010 American Thoracic Society
doi: 10.1164/rccm.200909-1420OC [/SIZE]
<table cellpadding="0" cellspacing="0"><tbody><tr><td><hr noshade="noshade" size="1">Original Article

</td></tr></tbody></table> Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection

<table border="0" cellpadding="0" cellspacing="0" width="800"><tbody><tr><td valign="TOP" width="670"><nobr>Thais Mauad¹</nobr>, <nobr>Ludhmila A. Hajjar²</nobr>, <nobr>Giovanna D. Callegari¹</nobr>, <nobr>Luiz F. F. da Silva¹</nobr>, <nobr>Denise Schout³</nobr>, <nobr>Filomena R. B. G. Galas²</nobr>, <nobr>Venancio A. F. Alves¹</nobr>, <nobr>Denise M. A. C. Malheiros¹</nobr>, <nobr>Jose O. C. Auler, Jr.²</nobr>, <nobr>Aurea F. Ferreira¹</nobr>, <nobr>Marcela R. L. Borsato¹</nobr>, <nobr>Stephania M. Bezerra¹</nobr>, <nobr>Paulo S. Gutierrez⁴</nobr>, <nobr>Elia T. E. G. Caldini¹</nobr>, <nobr>Carlos A. Pasqualucci¹^,5</nobr>, <nobr>Marisa Dolhnikoff¹</nobr> and <nobr>Paulo H. N. Saldiva¹</nobr> [SIZE=-1] ¹ Department of Pathology, ² Department of Anesthesiology, ³ Department of Preventive Medicine, Epidemiology Service, Hospital das Cl?nicas, ⁴ Laboratory of Pathology?Heart Institute, Hospital das Cl?nicas, and ⁵ Autopsy Service of Sao Paulo City, S?o Paulo University, S?o Paulo, Brazil [/SIZE]
[SIZE=-1]Correspondence and requests for reprints should be addressed to Thais Mauad M.D., Ph.D., Department of Pathology, S?o Paulo University Medical School, Av. Dr. Arnaldo, 455 room 1155, CEP 01246-903 S?o Paulo SP, Brazil. E-mail: tmauad@usp.br<script type="text/javascript"><!-- var u = "tmauad", d = "usp.br"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>[/SIZE]
<!-- ABS --> Rationale: There are no reports of the systemic human pathologyof the novel swine H1N1 influenza (S-OIV) infection.
Objectives: The autopsy findings of 21 Brazilian patients withconfirmed S-OIV infection are presented. These patients diedin the winter of the southern hemisphere 2009 pandemic, withacute respiratory failure.
Methods: Lung tissue was submitted to virologic and bacteriologicanalysis with real-time reverse transcriptase polymerase chainreaction and electron microscopy. Expression of toll-like receptor(TLR)-3, IFN-

, tumor necrosis factor-

, CD8⁺ T cells and granzymeB⁺ cells in the lungs was investigated by immunohistochemistry.
Measurements and Main Results: Patients were aged from 1 to68 years (72% between 30 and 59 yr) and 12 were male. Sixteenpatients had preexisting medical conditions. Diffuse alveolardamage was present in 20 individuals. In six patients, diffusealveolar damage was associated with necrotizing bronchiolitisand in five with extensive hemorrhage. There was also a cytopathiceffect in the bronchial and alveolar epithelial cells, as wellas necrosis, epithelial hyperplasia, and squamous metaplasiaof the large airways. There was marked expression of TLR-3 andIFN-

and a large number of CD8⁺ T cells and granzyme B⁺ cellswithin the lung tissue. Changes in other organs were mainlysecondary to multiple organ failure.
Conclusions: Autopsies have shown that the main pathologicalchanges associated with S-OIV infection are localized to thelungs, where three distinct histological patterns can be identified.We also show evidence of ongoing pulmonary aberrant immune response.Our results reinforce the usefulness of autopsy in increasingthe understanding of the novel human influenza A (H1N1) infection.

Key Words: autopsy ? virus ? diffuse alveolar damage ? bronchiolitis ? innate immunity

<table border="1" cellpadding="10"><tbody><tr bgcolor="#e1e1e1"><td>[SIZE=+1]AT A GLANCE COMMENTARY[/SIZE] Scientific Knowledge on the Subject
Most patients with H1N1infection present flulike symptoms with a benign course. Patientswith comorbidities may have a serious clinical presentationwith respiratory failure. The main cause of death is acute respiratorydistress syndrome. The pulmonary pathology of patients who diedwith the H1N1 infection is incompletely described.
What ThisStudy Adds to the Field
This study shows that the main pathologicalchanges associated with H1N1 infection are localized to thelungs, where three distinct histological patterns can be identified:diffuse alveolar damage (DAD), necrotizing bronchiolitis, andDAD with intense alveolar hemorrhage. There is also evidenceof ongoing pulmonary aberrant immune response
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[Treyfish]

Re: H1N1: une forme "rapidement fatale" de la maladie ? l'origine des d?c?s - American journal of Respiratory and Critical Care Medicine

Re: H1N1: une forme "rapidement fatale" de la maladie ? l'origine des d?c?s - American journal of Respiratory and Critical Care Medicine

A form "rapidly fatal" of H1N1?
NOUVELOBS.COM | 25.12.2009 | 12:37
According to a study published January 1 in the United States, would kill the virus in different ways. 21 cases of victims aged one to 68 years have been studied.



It would form a "rapidly fatal" virus, according to a study published on 1 January in the American Journal of Respiratory and Critical Care Medicine. Here, microscopic view of a culture of the virus H1N1.


(Reuters)
According to a study published Thursday in the U.S., people died of influenza H1N1 have contracted a form of "rapidly fatal" disease, which kills but in different ways. 21 cases of patients aged one to 68 years, died in July and August in Sao Paulo (Brazil) have been studied by researchers. All these 21 cases "presented as a progressive and rapidly fatal disease," according to the study published in the January 1 edition of the Journal of the American Society of Chest Diseases (American Society thracica, TTY) American Journal of Respiratory and Critical Care Medicine.


"Aberrant immune response"
All died due to severe lung damage, but these were of three types, according to the study which concludes that the H1N1 flu "killed in different ways. Some only had severe lung lesions, but in others they were also accompanied with bronchiolitis (inflammation of small airways), and among others, a "bleeding tendency" says Thais Mauad, associate professor at Department of Pathology, University of Sao Paulo, and lead author of the study. "It is important to bear in mind that patients with prior health problems must be properly monitored because they have an increased risk of severe infection with H1N1," said she. Sixteen of 21 patients studied by the research team were suffering from chronic conditions like heart disease or cancer.
An "aberrant immune response" has also been found in some patients, which "suggests that an exaggerated inflammatory response caused by viral infection could escalate and damage lung tissue, causing severe lung damage and respiratory failure fatal, "said John Heffner, ATS. :tiphat:http://tempsreel.nouvelobs.com/spec...724/une_forme_rapidement_fatale_du_h1n1_.html