BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in the United Kingdom. The five-year survival rate from CRC is only 10% when discovered at a late stage, but can exceed 90% if diagnosed early. Symptoms related to CRC can be non-specific, and therefore the decision to refer for a colonoscopy can be challenging. Breath analysis potentially offers a simple and quick method to detect CRC specific volatile organic compounds (VOCs) in breath. This protocol describes the COBRA2 study which aims to develop and validate the clinical prediction model (CPM) in the detection of CRC based on the breath test. An exploratory comparison between the breath test and faecal immunochemical test (FIT) will also be carried out to assess whether combining both tests improves diagnostic performance. METHODS: The COBRA2 study is a multicentre, case-control development and validation study. Breath samples will be collected from participants attending hospital for a planned colonoscopy (control group) or from participants with histologically confirmed colorectal adenocarcinoma (CRC group). A total of 720 participants (470 controls, 250 CRC) will be recruited. All participants will maintain a clear fluid diet for a minimum of 4-6 h prior to sampling, which will take place at outpatient clinics to avoid bowel preparation. The FIT result will be recorded where available. Breath samples will be analysed using gas chromatography-mass spectrometry to identify the VOCs present. Relationships between VOCs of interest and presence of CRC will be explored, and the CPM will be developed using statistical and machine learning methods. We will also assess whether incorporating FIT into the CPM improves diagnostic performance. The CPM will be subsequently validated in an independent sample of up to 250 participants (125 controls, 125 CRC) using the same case-control design and the potential clinical utility of decision rules for triaging will be assessed. If successful, broad validation in an unselected target population of symptomatic patients is required. DISCUSSION: The non-invasive breath test may provide direct patient benefit through earlier and accurate detection of CRC, and higher patient acceptability. It can help ensure timely secondary care referral, potentially translating to improved curative treatment and survival for patients. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT05844514).

• Klíčová slova
• Biomarkers, Breath test, Colorectal cancer, Detection, Diagnostic model, Volatile organic compounds,
• MeSH
• časná detekce nádoru * metody   MeSH
• dechové testy metody   MeSH
• kolonoskopie MeSH
• kolorektální nádory * diagnóza   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• studie případů a kontrol MeSH
• těkavé organické sloučeniny * analýza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• těkavé organické sloučeniny * MeSH

Growing evidence suggests that specific volatile organic compound (VOC) profiles may reflect key pathophysiological processes in Parkinson's disease (PD), including alterations in the microbiome, metabolism, and oxidative stress. Identifying reliable VOC biomarkers could enable non-invasive tests for early diagnosis, disease monitoring, and therapy evaluation. This review examines VOC analysis in biological matrices such as breath, skin, and stool, outlining current research and future applications in PD. We evaluate analytical techniques based on sensitivity, specificity, and clinical applicability. Additionally, we classify VOCs identified in previous studies alongside their proposed biological origins. Special attention is given to short-chain fatty acids, produced by the gut microbiome, a novel target in PD research. Our findings highlight the need for larger cohort studies and standardized protocols to advance VOC-based diagnostics in PD. Understanding the interplay between VOCs and PD may facilitate biomarker discovery, enhancing non-invasive diagnostic strategies and personalized disease management.

• Publikační typ
• časopisecké články MeSH

Selected ion flow tube mass spectrometry (SIFT-MS) is now recognized as the most versatile analytical technique for the identification and quantification of trace gases down to the parts-per-trillion by volume, pptv, range. This statement is supported by the wide reach of its applications, from real-time analysis, obviating sample collection of very humid exhaled breath, to its adoption in industrial scenarios for air quality monitoring. This review touches on the recent extensions to the underpinning ion chemistry kinetics library and the alternative challenge of using nitrogen carrier gas instead of helium. The addition of reagent anions in the Voice200 series of SIFT-MS instruments has enhanced the analytical capability, thus allowing analyses of volatile trace compounds in humid air that cannot be analyzed using reagent cations alone, as clarified by outlining the anion chemistry involved. Case studies are reviewed of breath analysis and bacterial culture volatile organic compound (VOC), emissions, environmental applications such as air, water, and soil analysis, workplace safety such as transport container fumigants, airborne contamination in semiconductor fabrication, food flavor and spoilage, drugs contamination and VOC emissions from packaging to demonstrate the stated qualities and uniqueness of the new generation SIFT-MS instrumentation. Finally, some advancements that can be made to improve the analytical capability and reach of SIFT-MS are mentioned.

• Klíčová slova
• SIFT‐MS, VOCs, cation and anion gas phase chemistry, nitrogen carrier gas, selected ion flow tube mass spectrometry, volatile organic compounds,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.

• MeSH
• dechové testy metody   MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• těkavé organické sloučeniny * analýza   MeSH
• tělesné tekutiny * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• těkavé organické sloučeniny * MeSH