title: Pulmonary changes in Norwegian fatal cases of pandemic influenza H1N1 (2009) infection: a morphologic and molecular genetic study.
abstract: During the pandemic outbreak of the 2009 swine influenza (A(H1N1)pdm09), 32 fatal cases occurred in Norway and 19 of these were included in this study.
  
  
  
  We characterised pulmonary changes in these fatal Norwegian cases.
  
  
  
  Upon hospitalisation, detailed clinical information and specimens from the upper and lower respiratory pathways were collected. At post-mortem, lung tissue was collected, formalin-fixed and paraffin-embedded. Immunohistochemical and light microscopic examination was performed to visualise the local expression of the A(H1N1)pdm09 virus. Reverse transcription-polymerase chain reaction (RT-PCR) and pyrosequencing of the non-fixed specimens allowed the identification of mutations in the influenza virus surface glycoprotein (haemagglutinin gene) particularly at position 222.
  
  
  
  The overall course of illness lasted from 2 to 40 days (median 9 days). Diffused alveolar damage (DAD) was evident in 11 cases, 4 of which had no apparent underlying illness. Obesity was prominent in 12 cases, where three individuals were classified as otherwise healthy. The HA D222G mutation was detected in six cases, 3 of which had no underlying illness. Immunohistochemistry showed the A(H1N1)pdm09 virus to be prominent at the site of inflammation both in close proximity to and inside alveolar structures in the lung tissue. In addition to a possible role for the HA D222G mutation, our findings indicate that host factors and underlying conditions in the infected individuals are fundamental for disease outcome in many cases. This study increases our understanding of determinants for the clinical outcome of pandemic influenza, which could guide future treatment.
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Voltersvik
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.|K. G. Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Aqrawi
authors.affiliation: WHO National Influenza Centre, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Susanne
authors.initials: S
authors.lastname: Dudman
authors.affiliation: WHO National Influenza Centre, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Hungnes
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Haukeland University Hospital, University of Bergen, Bergen, Norway.
authors.forename: Leif
authors.initials: L
authors.lastname: Bostad
authors.affiliation: The Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Brokstad
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway. Rebecca.Cox@uib.no.|K. G. Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway. Rebecca.Cox@uib.no.|Department of Research and Development, Haukeland University Hospital, Bergen, Norway. Rebecca.Cox@uib.no.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006760:Hospitalization; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D007251:Influenza, Human / Q000150:complications / Q000401:mortality* / Q000473:pathology* / Q000821:virology; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009664:Norway / Q000453:epidemiology; D009765:Obesity / Q000150:complications / Q000821:virology; D058873:Pandemics; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D012367:RNA, Viral
keywords: 2009 pandemic; HA pyrosequencing; immunohistochemistry; influenza; lung