Mechanical and Aerospace Engineering, University of California Davis, Davis, California, USA.
Veterans Affairs Northern California Health Care System, Mather, California, USA.
J Infect Dis. 2021 Nov 22;224(10):1742-1750. doi: 10.1093/infdis/jiab205.
Respiratory viral infections are common and potentially devastating to patients with underlying lung disease. Diagnosing viral infections often requires invasive sampling, and interpretation often requires specialized laboratory equipment. Here, we test the hypothesis that a breath test could diagnose influenza and rhinovirus infections using an in vitro model of the human airway.
Cultured primary human tracheobronchial epithelial cells were infected with either influenza A H1N1 or rhinovirus 1B and compared with healthy control cells. Headspace volatile metabolite measurements of cell cultures were made at 12-hour time points postinfection using a thermal desorption-gas chromatography-mass spectrometry method.
Based on 54 compounds, statistical models distinguished volatile organic compound profiles of influenza- and rhinovirus-infected cells from healthy counterparts. Area under the curve values were 0.94 for influenza, 0.90 for rhinovirus, and 0.75 for controls. Regression analysis predicted how many hours prior cells became infected with a root mean square error of 6.35 hours for influenza- and 3.32 hours for rhinovirus-infected cells.
Volatile biomarkers released by bronchial epithelial cells could not only be used to diagnose whether cells were infected, but also the timing of infection. Our model supports the hypothesis that a breath test could serve to diagnose viral infections.
呼吸道病毒感染很常见,对于患有基础肺部疾病的患者来说,这些感染可能具有潜在的破坏性。诊断病毒感染通常需要进行有创性采样,而解释结果通常需要专门的实验室设备。在这里,我们通过体外人呼吸道模型来检验以下假设,即呼吸测试能否用于诊断流感和鼻病毒感染。
用甲型 H1N1 流感病毒或鼻病毒 1B 感染培养的原代人气管支气管上皮细胞,并与健康对照细胞进行比较。在感染后 12 小时的时间点,使用热解吸-气相色谱-质谱法对细胞培养物的顶空挥发性代谢物进行测量。
基于 54 种化合物,统计模型区分了流感病毒和鼻病毒感染细胞与健康对照细胞的挥发性有机化合物图谱。流感病毒的曲线下面积值为 0.94,鼻病毒为 0.90,对照为 0.75。回归分析预测了细胞被感染前的时间,对于流感病毒和鼻病毒感染的细胞,其均方根误差分别为 6.35 小时和 3.32 小时。
支气管上皮细胞释放的挥发性生物标志物不仅可用于诊断细胞是否受到感染,还可用于诊断感染发生的时间。我们的模型支持了这样一种假设,即呼吸测试可用于诊断病毒感染。