Abstract
摘要:研究背景:呼吸器相關肺炎(ventilator-associated pneumonia)為重症病患死亡重要原因。早期診斷呼吸器相關肺炎可提供適當治療降低死亡率。發展非侵入性、高準確性之診斷方法有其重要性。研究目的:發展電子鼻診斷呼吸器相關肺炎吐氣試驗。合理性:細菌分解代謝路徑會產生揮發性有機化合物。電子鼻以感應器陣列測量揮發性有機化合物,可辨識不同致病菌產生之揮發性有機化合物。分析呼吸器相關肺炎致病菌所產生之揮發性有機化合物,最佳方式是蒐集肺泡氣體,以避免來自環境空氣的汙染,並可由下呼吸道取得最接近致病菌氣體。藉由分析肺泡氣體,可發展呼吸器相關肺炎呼氣診斷試驗。作業假說:細菌分解代謝過程會產生揮發性有機化合物,呼吸器相關肺炎致病菌會改變呼吸氣體揮發性有機化合物成份,以電子鼻分析揮發性有機化合物,可用於診斷呼吸器相關肺炎。研究方法:我們設計一系列步驟以驗證提出的假說。為發展呼氣試驗診斷呼吸器相關肺炎,需建立呼氣試驗採樣分析標準方法、驗證電子鼻測量結果可再現性、並交叉驗證診斷準確性。目標一:建立以電子鼻進行呼氣試驗標準方法研究將藉由監測呼吸管路二氧化碳濃度,由氣管內管蒐集肺泡氣體。以同一病患進行重復測量,驗證電子鼻測量結果之可重複性;並以電子鼻分析同一氣體樣本,於採樣當天、與採樣隔天進行重復分析,驗證電子鼻感應器反應結果之穩定性。目標二:驗證以電子鼻區辨呼吸器相關肺炎致病菌之準確性以病例對照研究設計,納入150 名呼吸器相關肺炎病患為病例組,以150 名無感染性疾病之使用呼吸器病患為對照組,區辨5 種主要呼吸器相關肺炎致病菌及對照組所產生之揮發性有機化合物差異,以建立以電子鼻診斷呼吸器相關肺炎預測模式,以氣相層析質譜儀分析潛在代謝產物成份。資料將以2:1比例分為訓練數據集與驗證數據集,分別用於預測模式建立、與預測準確性驗證。研究將以取自下呼吸道分泌物之細菌培養結果為黃金標準,驗證呼氣試驗診斷之準確性。預期結果:電子鼻可區辨不同致病菌感染產生之揮發性有機化合物,應用於呼吸器相關肺炎診斷。
Abstract: Background: Ventilator-associated pneumonia (VAP) is a significant cause of mortality in critically illpatients. Early diagnosis of VAP is important to provide appropriate treatment and reduce mortality.Developing a non-invasive and highly accurate diagnostic method is warranted.Objectives: The objective of this study is to develop a breath test for VAP using an electronic nose.Rationale: Bacteria can produce volatile organic compounds (VOCs) via catabolic pathway. An electronicnose uses sensor arrays to measure VOCs and recognize the pattern of VOCs derived from differentpathogens. To measure the VOCs of VAP, the best way is to collect the alveolar air because it originates fromthe lower respiratory airways near pathogens and the method can prevent contamination from ambient air.Analysis of alveolar air could provide a breath test for the diagnosis of VAP.Working hypothesis: Many bacterial species can produce volatile metabolites via catabolic pathways.Pathogens of VAP could alter the VOCs in the breath. The VOCs can be analyzed by an electronic nose todiagnose VAP.Experimental approach: We designed a successive study to test the proposed hypothesis. To apply thebreath test to diagnose VAP, we need to establish a standardized method of sampling and analysis, assess thereproducibility of sensor responses of the electronic nose, and validate the diagnostic accuracy.Aim 1. To establish a standardized breath test using an electronic noseWe will collect alveolar air from endotracheal tubes by visual monitoring of CO2 concentrations in therespiratory flow. We will have repeated measurement in the same study subjects to test the reproducibility oftest results using an electronic nose. We will also assess the within-day and between-day repeatability ofmeasurements of the same air sample to determine the reliability of the electronic nose sensor responses.Aim 2. To validate the accuracy of the electronic nose in discriminating the causative pathogens of VAPWe have designed a case-control study. Study will recruit 150 patients with VAP as the case group and 150ventilated patients without infectious diseases as the control group to discriminate VOCs derived from fivemajor pathogens of VAP. We will build a prediction model for VAP using the electronic nose and analyze theair by gas chromatography/mass spectrometry to explore potential biomarkers. Data will be split into atraining set for model building and a validation set to assess the predictive ability at a ratio of 2:1. Usingmicrobiological diagnosis based on the culture of lower respiratory tract secretions as the gold standard, wewill assess the accuracy of the breath test.Anticipated results: An electronic nose can discriminate the distinct patterns of VOCs derived from differentpathogens and be applied to diagnose VAP.
Keyword(s)
電子鼻
呼氣試驗
呼吸器相關肺炎
揮發性有機化合物
electronic nose
breath test
ventilator-associated pneumonia
volatile organic compounds