Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine-origin influenza type A/H1N1 and acute respiratory failure

Capelozzi, Vera Luiza; Parra, Edwin Roger; Ximenes, Manoel; Bammann, Ricardo Helbert; Barbas, Carmen Silvia Valente; Duarte, Marid Irmd Seixas

Recently, a novel swine-origin influenza A (H1N1) virus with molecular features of North American and Eurasian swine, avian, and human influenza viruses [1] [2] [3] [4] has been associated with an outbreak of respiratory disease. According to the World Health Organization (WHO), between 25 April and 11 October 2009, 399,232 confirmed cases of H1N1 influenza virus and 4,735 deaths occurred throughout the world. 5 Brazil reported 1,528 deaths up to 10 November 2009. 6 Swine-origin influenza A (H1N1) virus infection can cause severe acute respiratory failure (ARF), requiring admission to an intensive care unit (ICU) in 15-30% of previously healthy young to middle-aged people. 3, 4, 7, 8 Death may occur when co-infections or lung injury prevail over the immune response, resulting in a progressive worsening of lung function (low compliance and oxygenation). Early diagnosis and a complete understanding of the pathological features of the H1N1 virus are important to help to improve treatment and the prognosis of this lethal disease. Analysis of the lung tissue from an open lung biopsy (OLB) of these severe cases can help in understanding the pathogenesis of this severe and sometimes fatal development. Until now, no reports of OLB findings used to guide the treatment of patients with H1N1 pneumonitis have been published, although according to many authors OLB is safe and diagnostically useful in patients with ARF, enabling appropriate therapy. [9] [10] [11] [12] The pathogenesis of ARF associated with swine-origin influenza virus (S-OIV) infection in humans is unknown. The influenza virus triggers pulmonary inflammation owing to an infiltration of inflammatory cells and an immune response. Bronchial epithelial cells are the primary target and the principal host for the virus. 13, 14 Normally, influenza viruses are recognized and destroyed by innate immune mechanisms which involve macrophages, interferon (IFN) a, b and other cytokines, natural killer (NK) cells and complement. When influenza viruses escape from these early defense mechanisms, they are captured and eliminated by adaptive immune mechanisms, where T and B cells and their antigen-specific effectors (cytotoxic T lymphocytes, cytokines such as IFNc and antibodies) target the virus. Additionally, antigen-specific memory cells (T and B cells) are involved in the prevention of the subsequent viral infection. 14 Thus, pathological findings obtained by an OLB, coupled to ultrastructural and immunologic analysis, may have an impact on decisions about changes in treatment strategies employed for these critically ill patients, and also provide a greater understanding of the pathophysiology of S-OIV infection. The objective of this study was to analyze pathologically and ultrastructurally S-OIV lung infection and the pulmonary immune response in a series of five cases with OLB.