以吐氣代謝體學偵測氣喘學童之呼吸危害研究

Abstract

空氣污染是環境中對健康的一個主要危害來源。高濃度的空氣污染物會危害人們的健康，並造成許多疾病。尤其對於肺功能差的氣喘兒童而言更為危險。但是目前空氣污染成分（揮發性有機化合物（VOC））對於健康的危害仍需要採取進一步研究。藉由人體呼出的VOC作為代謝體學的生物標誌物可以評估暴露汙染或呼吸道病理與生理變化，作為協助診斷的工具。本研究包括兩個研究目的：（1）透過氣喘兒童進行人體吐氣分析來評估VOC的暴露情形，（2）探討可能的氣喘生物標誌物，以提供吐氣中目標代謝物特徵的氣喘兒童的診斷及分型參考。 我們在臺灣的兩個研究地點對氣喘學生和健康學生進行了橫斷面研究和病例對照研究。我們收集了空氣污染調查問卷並提供了肺功能與吐氣一氧化氮的測量。接著收集受試者的呼氣，透過氣相層析質譜儀（GC/MS）以目標定量和半定量的方法進行氣體成分及濃度分析。 本研究的吐氣分析可以檢測出暴露於低濃度的空氣污染VOC。我們發現在人體呼出的揮發性有機化合物濃度高低與氣喘的肺功能數值相關症狀之間呈現負相關。在人體吐氣中發現VOC大多來自於室內空氣污染物的暴露。我們發現3,3-二甲基己烷作為氧化壓力的指標，在氣喘兒童的吐氣中有較高的濃度表現（t-test p = 0.000; Fold Change = 3.171, p = 0.001），且超過0.6的曲線下面積具有良好的氣喘預測準確與區辨性（AUC = 0.69, p = 0.000）。我們同時發現3,3-二甲基己烷和異戊二烯在有氣道發炎的較高呼氣一氧化氮濃度和肥胖之氣喘病童呈現正向劑量反應效應（AUC = 0.69, 線性趨勢p value = 0.000; AUC = 0.69, 線性趨勢p value = 0.005）。在控制了空氣污染物引起的汙染物干擾因子後，我們發現2,4-二甲基庚烷在氣喘兒童的吐氣中有較高的濃度表現（t-test p value = 0.001; Fold Change = 7.117, p value = 0.001），可能是氣喘的生物標誌物。 我們提供了低濃度的VOC暴露會影響兒童肺功能的證據，並且透過定量和半定量來分析人體吐氣，評估了氣喘兒童的潛在呼氣生物標誌物，以應用於未來氣喘評估和診斷分型的參考。未來可透過定量環境監測器，進一步評估環境空氣汙染濃度與呼出氣體汙染物之間的直接相關性，並進一步探討氣喘的潛在生物標誌物。

Air pollution is a major environmental hazard to respiratory health. High levels of air pollutants can harm people’s health and cause poor lung function in asthmatic children. However, the component of air pollution level (volatile organic compounds (VOCs)) effect on respiratory health still needs further approach. Exhaled VOCs as a metabolomics biomarker can provide a diagnostic opportunity to assess air pollution exposure and pathophysiological changes in the respiratory system. The aims of our study include two objectives: (1) To assess the respiratory function and the effect of VOC exposure by using exhaled breath analysis in asthmatic children, (2) To develop exhaled breath metabolites as possible biomarkers for the diagnosis and phenotypes classification in asthmatic children. We conducted a cross-sectional study and case-control study between asthmatic students and healthy students in two study sites in Taiwan. We collected air pollution and the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, lung function measurement, and Fractional Exhaled Nitric Oxide (FeNO). The exhaled breath of the subjects was collected then analyzed with the targeted quantitative and semi-quantitative method by gas chromatography /mass spectrometer (GC/MS). A low level of VOC concentrations of air pollutants can be detected by using exhaled breath analysis. We found negative correlations between exhaled VOCs and pulmonary function values. Indoor air pollution plays a role in exhaled-VOC exposure. We found 3,3-dimethylhexane as an oxidative stress marker and correlated asthma severity, which found higher concentration in asthma patients (t-test p = 0.000; Fold Change = 3.171, p = 0.001). The Youden index with area under the curve (AUC) over 0.6 was used to determine the cutoff 3,3-dimethylhexane values (AUC = 0.69, p = 0.000) to predict asthma patients and normal healthy subjects. We found 3,3-dimethylhexane (AUC = 0.69, p for trend = 0.000) and Isoprene (AUC = 0.69, p for trend = 0.005) were positive dose-response association in having higher FeNO and obesity of the asthmatic children. After avoiding the effect of air pollutants-induced VOCs, we found 2,4-dimethylheptane have a higher concentration in the exhaled breath of the asthmatic children (t-test p value = 0.001; Fold Change = 7.117, p value = 0.001), which could be indicated as a potential asthmatic biomarker. We provided evidence of VOC exposure can affect pulmonary function in children. Potential biomarkers of asthmatic children were estimated for asthma assessment and asthma phenotypes classification by conducted exhaled breath with targeted quantitative analysis. In the future, a quantitative environmental monitor can incorporate personal evaluation with exhaled pollutant exposure in asthmatic biomarkers are needed.