Monitoring Diurnal Changes in Exhaled Human Breath

The development of noninvasive analytical techniques is of interest to the field of chronobiology, in order to reveal the human metabolome that seems to show temporal patterns and to predict internal body time. We report on the real-time mass spectrometric analysis of human breath as a potential method to be used in this field. The breath of 12 subjects was analyzed during 9 days by secondary electrospray ionization-mass spectrometry (SESI-MS). The samples were collected during four time slots: morning (8:00–11:00), before lunch (11:00–13:00), after lunch (13:00–15:00), and late afternoon (15:00–18:00). A total of 203 mass spectra were statistically analyzed. Univariate analysis revealed a number of features with a marked temporal behavior. Principal component analysis/canonical analysis showed a clear temporal evolution of the breath patterns. A blind cross-validation yielded 84% of correct classifications of the time slot at which the breath samples were collected. We conclude that this approach seems to have potential for the investigation of biological clocks, including the description of internal body time, which may have important implications for the timing of pharmacotherapy.

非侵入性分析技术的研发受到时间生物学（chronobiology）领域的广泛关注，其目标在于揭示呈现出时间节律特征的人类代谢组，并预测机体内部时间。本研究报道了将实时质谱分析技术应用于人类呼气检测的方案，作为该领域的潜在应用方法。研究对12名受试者在9天内的呼气样本进行了检测，采用的技术为二次电喷雾电离质谱（secondary electrospray ionization-mass spectrometry，SESI-MS）。样本采集分为四个时段：上午（8:00–11:00）、午餐前（11:00–13:00）、午餐后（13:00–15:00）及傍晚（15:00–18:00）。最终共纳入203张质谱图进行统计分析。单变量分析结果显示，存在多个具有显著时间节律特征的质谱特征。主成分分析/典范分析显示，呼气代谢模式呈现出明确的时间演化规律。盲法交叉验证结果表明，对呼气样本采集时段的正确分类准确率可达84%。本研究结论认为，该方法在生物节律时钟研究中具备应用潜力，可用于阐释机体内部时间，这一发现对于药物治疗的给药时机选择具有重要指导意义。