title: Lung pathology in fatal novel human influenza A (H1N1) infection.
abstract: BACKGROUND
  There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection.
  
  
  OBJECTIVE
  The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure.
  
  
  METHODS
  Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry.
  
  
  RESULTS
  Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diffuse alveolar damage was present in 20 individuals. In six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-gamma and a large number of CD8(+) T cells and granzyme B(+) cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure.
  
  
  CONCLUSIONS
  Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, 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 increasing the understanding of the novel human influenza A (H1N1) infection.
authors.affiliation: Department of Pathology, São Paulo University, Brazil. tmauad@usp.br
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.forename: Ludhmila A
authors.initials: LA
authors.lastname: Hajjar
authors.forename: Giovanna D
authors.initials: GD
authors.lastname: Callegari
authors.forename: Luiz F F
authors.initials: LF
authors.lastname: da Silva
authors.forename: Denise
authors.initials: D
authors.lastname: Schout
authors.forename: Filomena R B G
authors.initials: FR
authors.lastname: Galas
authors.forename: Venancio A F
authors.initials: VA
authors.lastname: Alves
authors.forename: Denise M A C
authors.initials: DM
authors.lastname: Malheiros
authors.forename: Jose O C
authors.initials: JO
authors.lastname: Auler
authors.forename: Aurea F
authors.initials: AF
authors.lastname: Ferreira
authors.forename: Marcela R L
authors.initials: MR
authors.lastname: Borsato
authors.forename: Stephania M
authors.initials: SM
authors.lastname: Bezerra
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Gutierrez
authors.forename: Elia T E G
authors.initials: ET
authors.lastname: Caldini
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pasqualucci
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolhnikoff
authors.forename: Paulo H N
authors.initials: PH
authors.lastname: Saldiva
mesh_terms: D000293:Adolescent; D000368:Aged; D001344:Autopsy; D001990:Bronchiolitis, Viral / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology*; D055815:Young Adult