Department Respiratory Medicine, Amsterdam University Medical Centres - loc. AMC, University of Amsterdam, Amsterdam, Netherlands.
Department Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam University Medical Centres, Amsterdam, the Netherlands.
J Cyst Fibros. 2022 Jan;21(1):e28-e34. doi: 10.1016/j.jcf.2021.04.015. Epub 2021 May 18.
Pseudomonas aeruginosa (PA) is an important respiratory pathogen for cystic fibrosis (CF) patients. Routine microbiology surveillance is time-consuming, and is best performed on expectorated sputum. As alternative, volatile organic compounds (VOCs) may be indicative of PA colonisation. In this study, we aimed to identify VOCs associated with PA in literature and perform targeted exhaled breath analysis to recognize PA positive CF patients non-invasively.
This study consisted of 1) a literature review to select VOCs of interest, and 2) a cross-sectional CF study. Definitions used: A) PA positive, PA culture at visit/chronically; B) PA free, no PA culture in ≥12 months. Exhaled VOCs were identified via quadrupole MS. The primary endpoint was the area under the receiver operating characteristics curve (AUROCC) of individual VOCs as well as combined VOCs against PA culture.
241 VOCs were identified in literature, of which 56 were further evaluated, and 13 could be detected in exhaled breath in our cohort. Exhaled breath of 25 pediatric and 28 adult CF patients, PA positive (n=16) and free (n=28) was available. 3/13 VOCs were significantly (p<0.05) different between PA groups in children; none were in adults. Notably, a composite model based on 5 or 1 VOC(s) showed an AUROCC of 0.86 (CI 0.71-1.0) and 0.87 (CI 0.72-1.0) for adults and children, respectively.
Targeted VOC analysis appears to discriminate children and adults with and without PA positive cultures with clinically acceptable sensitivity values.
铜绿假单胞菌（PA）是囊性纤维化（CF）患者的重要呼吸道病原体。常规微生物学监测既耗时又费力，最好在咳出的痰液上进行。作为替代方法，挥发性有机化合物（VOCs）可能是 PA 定植的指示物。在这项研究中，我们旨在确定文献中与 PA 相关的 VOCs，并进行靶向呼气分析，以无创方式识别 PA 阳性 CF 患者。
本研究包括 1）文献综述以选择有意义的 VOCs，和 2）一项 CF 的横断面研究。使用以下定义：A）PA 阳性，就诊/慢性时 PA 培养阳性；B）PA 阴性，≥12 个月内无 PA 培养。通过四级杆 MS 鉴定呼气 VOCs。主要终点是个体 VOCs 以及组合 VOCs 对 PA 培养的接受者操作特征曲线（AUROCC）的曲线下面积（AUROCC）。
在文献中确定了 241 种 VOCs，其中 56 种进一步进行了评估，并且在我们的队列中可以检测到 13 种在呼气中。25 名儿科和 28 名成年 CF 患者的呼气，PA 阳性（n=16）和 PA 阴性（n=28）可用。在儿童中，有 3/13 VOCs 在 PA 组之间有显著差异（p<0.05）；在成人中没有。值得注意的是，基于 5 种或 1 种 VOC(s)的综合模型在成人和儿童中的 AUROCC 分别为 0.86（CI 0.71-1.0）和 0.87（CI 0.72-1.0）。
靶向 VOC 分析似乎可以区分有和没有 PA 阳性培养的儿童和成人，具有可接受的临床灵敏度值。
