Use of an Electronic Nose to Evaluate Disease Activity in Ulcerative Colitis
使用電子鼻評估潰瘍性結腸炎的疾病活動
Zibing J. Woodward, Kevin Piro, Sarah Lee, Emile Latour, Jodi Lapidus, Suni Wilson,
David Lieberman, Judith Collins, Kian Keyashian, Nir Modiano
Background and AimsAssessment of disease activity in inflammatory bowel disease (IBD) reflects a major challenge in clinical practice, relying on invasive endoscopic evaluation, expensive imaging tests and biomarkers that are difficult to obtain in a timely fashion. Cyranose 320 is an electronic nose that senses volatile organic compounds; it has been previously used to distinguish between malignancies, inflammatory states and infections. In this proof of concept study, we analyzed the urine headspace of active and inactive ulcerative colitis (AUC, IAUC) patients (pts) as well as non-IBD controls with Cyranose in an effort to differentiate between groups to enable real-time disease assessment. Methods Urine samples were collected from consecutive UC pts seen in IBD clinic and during inpatient admissions; control subjects were those undergoing outpatient upper endoscopy for nonmalignant indications. AUC pts were those with moderate activity classified as a Partial Mayo score of ³ 5 or Full Mayo score of ³ 6, inactive UC were those with a Partial Mayo score of 0 or 1 and endoscopic Mayo Score of 0 or 1. The urine samples were stored in a-70°C freezer until the analysis was carried out. At that time, samples were thawed in a 40°C water bath and handled in a tissue culture laminar flow hood; urine headspace was analyzed by Cyranose according to machine protocol. The raw data collected from the 32 proprietary sensors were then analyzed using one-way analysis of variance (ANOVA), Canonical discriminant analysis (CDA) and logistic regression.
炎癥性腸病(IBD)疾病活動評估反映了臨床實踐中的一個主要挑戰，依賴于侵入性內鏡評估、昂貴的成像測試和難以及時獲得的生物標志物。Cyranose 320是一種電子鼻，能感知揮發性有機化合物；它以前被用來區分惡性腫瘤、炎癥狀態和感染。在這項概念驗證研究中，我們分析了活動性和非活動性潰瘍性結腸炎(AUC，IAUC)患者(PTS)和非IBD對照者使用Cyranose 320電子鼻尿液頂空分析，以區分各組，以便進行實時疾病評估。方法從IBD門診及住院期間連續出現的UC患者中采集尿液標本，對照組為非惡性適應癥門診上內鏡檢查。AUC評分為中度活動組，部分梅奧評分為3.5分或全部梅奧評分為3.6分；非活動組，部分梅奧評分為0或1分，內鏡梅奧評分為0或1分。尿液樣本儲存在-70°C的冷凍室中，直到進行分析。當時，樣品在40°C水浴中解凍，并在組織培養層流罩中處理；根據機器方案，用Cyranose尿液頂空分析。然后采用方差分析(ANOVA)、標準判別分析(CDA)和邏輯回歸對32個專有傳感器的原始數據進行分析。
Results A total of 41 samples were analyzed: 12 pts with AUC, 14 with IAUC and 15 controls. One-way ANOVA showed a statistically significant difference between group means for sensors 5-9, 11, 23, 29 and 31. False discovery rate was calculated to be < 1.0% for sensors 6 and 31, indicating a significant difference between group means using these sensors. The importance of sensors 6 and 31 was also shown using Random forest, a recursive partitioning approach. Canonical discriminant analysis shows a significant separation between the three groups (Figure 1). Logistic regressions using only sensors 6 and 31 were able to differentiate between pts with AUC and IAUC with good accuracy (Area under the Receiver Operating Characteristic curve - AUROC = 0.80). Similarly, these sensors were also able to distinguish between AUC and control pts (AUROC = 0.85), IAUC and controls (AUROC = 0.86) as well as UC pts as a whole and controls (AUROC = 0.78; Figure 2).
共分析41個樣本：12個AUC患者，14個IAUC患者和15個對照組。單因素方差分析顯示，傳感器5-9、11、23、29和31的組間平均值存在統計學顯著差異。對于傳感器6和31，錯誤發現率計算為<1.0%，表明使用這些傳感器的組間平均值存在顯著差異。傳感器6和31的重要性是還顯示了使用隨機林的遞歸分區方法。典型判別分析顯示三組之間存在顯著的分離(圖1)。僅使用傳感器6和31的邏輯回歸能夠很好地區分具有AUC和IAUC的PTS(接收器操作特性曲線下的面積-AUROC=0.80)。同樣，這些傳感器還能夠區分AUC和對照組(AUROC=0.85)、IAUC和對照組(AUROC=0.86)以及UC整體和對照組(AUROC=0.78；圖2)。
Conclusion Cyranose 320 is a novel technology for analyzing volatile organic compound profiles. This study shows it can be used to distinguish between pts with active and inactive UC as well as those without IBD. Cyranose may become a useful tool for point-of-care assessment of IBD disease activity. Larger studies are required to validate these findings.
Cyranose 320是一種分析揮發性有機化合物分布的新技術。這項研究表明，它可以用來區分有活動和不活動UC的PTS以及沒有IBD的PTS。需要更多的研究來驗證Cyranose 成為護理點評估IBD疾病活動新工具
