Lung histopathological findings in fatal pandemic influenza A (H1N1)

Med Intensiva. 2012 Jan-Feb;36(1):24-31. doi: 10.1016/j.medin.2011.10.005. Epub 2011 Dec 10.

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 and patients: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alveolar Epithelial Cells / virology
  • Antiviral Agents / therapeutic use
  • Consensus Sequence
  • Cross Reactions
  • Fatal Outcome
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype* / immunology
  • Influenza A Virus, H1N1 Subtype* / isolation & purification
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza, Human / complications
  • Influenza, Human / drug therapy
  • Influenza, Human / pathology*
  • Influenza, Human / virology
  • Lung / pathology*
  • Lung / virology
  • Macrophages / virology
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Nitric Oxide Synthase Type II / analysis
  • Nucleocapsid Proteins
  • Oxidative Stress
  • Pregnancy
  • Pregnancy Complications, Infectious / pathology
  • Pregnancy Complications, Infectious / virology
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / immunology
  • Respiration, Artificial
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / pathology
  • Respiratory Distress Syndrome / therapy
  • Respiratory Distress Syndrome / virology
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Viral Core Proteins / analysis
  • Viral Core Proteins / immunology
  • Young Adult

Substances

  • Antiviral Agents
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • RNA-Binding Proteins
  • Viral Core Proteins
  • 3-nitrotyrosine
  • Tyrosine
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II