title: Lung histopathological findings in fatal pandemic influenza A (H1N1).
abstract: OBJECTIVE
  To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue.
  
  
  METHODS
  Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens.
  
  
  RESULTS
  Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy.
  
  
  CONCLUSIONS
  Lung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes.
authors.affiliation: Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Nin
authors.forename: C
authors.initials: C
authors.lastname: Sánchez-Rodríguez
authors.forename: L S
authors.initials: LS
authors.lastname: Ver
authors.forename: P
authors.initials: P
authors.lastname: Cardinal
authors.forename: A
authors.initials: A
authors.lastname: Ferruelo
authors.forename: L
authors.initials: L
authors.lastname: Soto
authors.forename: A
authors.initials: A
authors.lastname: Deicas
authors.forename: N
authors.initials: N
authors.lastname: Campos
authors.forename: O
authors.initials: O
authors.lastname: Rocha
authors.forename: D H
authors.initials: DH
authors.lastname: Ceraso
authors.forename: M
authors.initials: M
authors.lastname: El-Assar
authors.forename: J
authors.initials: J
authors.lastname: Ortín
authors.forename: P
authors.initials: P
authors.lastname: Fernández-Segoviano
authors.forename: A
authors.initials: A
authors.lastname: Esteban
authors.forename: J A
authors.initials: JA
authors.lastname: Lorente
mesh_terms: D000293:Adolescent; D000328:Adult; D056809:Alveolar Epithelial Cells / Q000821:virology; D000998:Antiviral Agents / Q000627:therapeutic use; D016384:Consensus Sequence; D003429:Cross Reactions; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D008168:Lung / Q000473:pathology* / Q000821:virology; D008264:Macrophages / Q000821:virology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D019590:Nucleocapsid Proteins; D018384:Oxidative Stress; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology / Q000821:virology; D016601:RNA-Binding Proteins / Q000032:analysis / Q000276:immunology; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014758:Viral Core Proteins / Q000032:analysis / Q000276:immunology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II