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Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection

¹ Department of Pathology, ² Department of Anesthesiology, ³ Department of Preventive Medicine, Epidemiology Service, Hospital das Clínicas, ⁴ Laboratory of Pathology—Heart Institute, Hospital das Clínicas, and ⁵ Autopsy Service of Sao Paulo City, São Paulo University, São Paulo, Brazil

Correspondence and requests for reprints should be addressed to Thais Mauad M.D., Ph.D., Department of Pathology, São Paulo University Medical School, Av. Dr. Arnaldo, 455 room 1155, CEP 01246-903 São Paulo SP, Brazil. E-mail: tmauad{at}usp.br

Rationale: There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection.

Objectives: 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-, tumor necrosis factor-, CD8⁺ T cells and granzyme B⁺ cells in the lungs was investigated by immunohistochemistry.

Measurements and Main 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- 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.

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

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Most patients with H1N1 infection present flulike symptoms with a benign course. Patients with comorbidities may have a serious clinical presentation with respiratory failure. The main cause of death is acute respiratory distress syndrome. The pulmonary pathology of patients who died with the H1N1 infection is incompletely described. What This Study Adds to the Field This study shows that the main pathological changes associated with H1N1 infection are localized to the lungs, where three distinct histological patterns can be identified: diffuse alveolar damage (DAD), necrotizing bronchiolitis, and DAD with intense alveolar hemorrhage. There is also evidence of ongoing pulmonary aberrant immune response.

 

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				S. Mukhopadhyay, A. T. Philip, and R. Stoppacher Pathologic Findings in Novel Influenza A (H1N1) Virus ("Swine Flu") Infection: Contrasting Clinical Manifestations and Lung Pathology in Two Fatal Cases Am J Clin Pathol, March 1, 2010; 133(3): 380 - 387. [Abstract] [Full Text] [PDF]