Department of Pathology, São Paulo University, Brazil.
Am J Respir Crit Care Med. 2010 Jan 1;181(1):72-9. doi: 10.1164/rccm.200909-1420OC. Epub 2009 Oct 29.
There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection.
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.
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-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry.
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-gamma 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.
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.
目前尚无关于新型猪源性 H1N1 流感（S-OIV）感染的人体系统性病理学报道。
本研究报道了 21 例经实验室确诊的 S-OIV 感染巴西患者的尸检结果。这些患者均死于南半球 2009 年流感大流行期间，因急性呼吸衰竭死亡。
对肺组织进行病毒学和细菌学分析，采用实时逆转录聚合酶链反应和电子显微镜检测方法。通过免疫组织化学方法检测肺组织中 Toll 样受体（TLR）-3、IFN-γ、肿瘤坏死因子-α、CD8+T 细胞和颗粒酶 B+细胞的表达情况。
患者年龄 168 岁（72%为 3059 岁），男性 12 例。16 例患者存在基础疾病。20 例患者表现为弥漫性肺泡损伤，其中 6 例合并坏死性细支气管炎，5 例合并广泛出血。支气管和肺泡上皮细胞也存在细胞病变效应，同时有气道上皮坏死、增生和鳞状化生。肺组织中 TLR-3 和 IFN-γ表达明显，大量 CD8+T 细胞和颗粒酶 B+细胞浸润。其他器官的改变主要继发于多器官功能衰竭。
尸检显示，S-OIV 感染的主要病变局限于肺部，可识别出三种不同的组织学模式。我们还发现肺部存在持续的异常免疫反应。本研究结果进一步证实了尸检在加深对新型甲型 H1N1 流感感染认识方面的重要性。
