Volatile Organic Compounds Analysis by PTR-TOF-MS for Screening Respiratory Infections Using Exhaled Breath.

Official title

Volatile Organic Compounds Analysis for Rapid Testing Using EXhaled Breath for Respiratory Infection

Overview

Emerging respiratory diseases are a global health threat. Viruses such as influenza and coronaviruses have been the main cause of pandemics over the last century. In general, the impact of these respiratory infections is not limited to pandemic risks. Indeed, some pathogens also induce seasonal epidemics with a significant medical and economic burden. It is therefore essential to strengthen global surveillance, warning systems and early diagnosis capabilities for pathogens responsible for respiratory infections. One promising and recognized approach is the analysis of exhaled air, which contains a complex mixture of volatile organic compounds (VOCs), also known as the "volatilome". The volatilome is influenced by the patient's metabolism, immune system and microbiome. It can be disturbed by the presence of a pathogen. A possible approach to study the human volatilome is called the "on-line" method. Among the technologies capable of performing online analysis, analyzers using TOF (time-of-flight) technology separate ions according to velocity differences after acceleration by a fixed potential, and then measure all mass/charge ratios simultaneously. The data obtained takes the form of a mass spectrum composed of a multitude of peaks representing the abundance of each detected chemical species contained in the exhalation. The sensitivity and measurement speed of instruments using PTR-TOF-MS (Proton Transfer Reaction - Time of Flight - Mass spectrometer) technology enable real-time monitoring of the exhalation process, making it possible to analyze exhaled air as a function of time. PTR-TOF-MS instruments are usually compact in design, enabling them to be deployed in environments such as hospital emergency wards or mass screening centers. The aim of the VORTEX-1 study is to include patients presenting with signssymptoms of respiratory infections, irrespective of microbiological etiology, to approximate a routine clinical context, thus including infections of various viral or bacterial origins. In addition, a so-called "control" group will also be sampled, made up ofcomposed by healthy subjects (with nowithout respiratory infections or serious or chronic pathologies at the time of sampling). In parallel with the study of the chemical composition of the exhaled air of these patients, and to further our understanding of the factors influencing the volatilome, a combined exploratory analysis of the respiratory microbiota, the host response at the time of infection, and the pathogen(s) responsible for the infectious episode is required. To date, no such analysis exists in the scientific literature, probably due to the technical and logistical complexity of integrating data from multiple sources and the lack of a multidisciplinary consortium with the necessary expertise.In parallel with the study of the chemical composition of the exhaled air of these patients, and in order to go further in understanding the factors influencing the volatilome, a combined exploratory analysis of the respiratory microbiota, the host response at the time of infection and the pathogen(s) responsible for the infectious episode is required. To date, no such analysis exists in the scientific literature, probably due to the technical and logistical complexity of integrating data from multiple sources, but also to the absence of a multidisciplinary consortium capable of bringing together all the necessary expertise within the same project. The detection of specific VOCs could considerably improve and facilitate the diagnosis of these respiratory diseasesinfections. This research could revolutionize the diagnosis of respiratory infections by offering a rapid, non-invasive and easily scalable alternative to conventional diagnostic methods such as PCR tests, which require nasopharyngeal sampling. In parallel with the study of the chemical composition of the exhaled air of these patients, and to further our understanding of the factors influencing the volatilome, a combined exploratory analysis of the respiratory microbiota, the host response at the time of infection, and the pathogen(s) responsible for the infectious episode is required. To date, no such analysis exists in the scientific literature, probably due to the technical and logistical complexity of integrating data from multiple sources and the lack of a multidisciplinary consortium with the necessary expertise. The detection of specific VOCs could considerably improve and facilitate the diagnosis of these respiratory infections. by offering a rapid, non-invasive and easily scalable alternative to conventional diagnostic methods such as PCR tests.

Interventions

• Device Volatile Organic compounds (VOC) analysis in Exhaled breath using PTR-TOF-MS
  The collection and analysis of exhaled air for VOC detection is a non-invasive, painless procedure that will be carried out online and summarised as follows: . The patient's exhaled air is collected directly in the analyzer using disposable mouthpieces. 2\. Real-time chemical analysis of exhaled air over a few seconds (breath duration) using PTR-TOF-MS. 3\. Processing raw data to establish the chemical composition of VOCs. 4. Statistical analysis of all generated data to identify specific VOC

Primary outcome measures

• Comparison and differentiation between patients presenting symptoms of acute respiratory infection (ARI) and a control group of healthy subjects [Time frame: DAY 1]

Secondary outcome measures (4)

• Validation of descriptive analyses of exhaled air test based on aggregated diagnostic parameters compared with those of the current biological reference standard for respiratory infection. [Time frame: DAY 1]
• Description of the breath composition based on the area under each peak of exhaled air according to six levels of classification [Time frame: DAY 1]
• Description of the breath composition based on the AUC of each peak [Time frame: DAY 1]
• Description of the breath composition based on the AUC of each peak [Time frame: DAY 1]

Eligibility criteria

Eligibility Criteria \*

• Inclusion Criteria \* :

• Age ≥ 18 years old
• Having signed a written informed consent
• With clinical signs of acute respiratory infection, or with a clinical presentation of acute community-acquired pneumonia, nasopharyngitis, angina or laryngitis (except for healthy patients)
• Exclusion Criteria \* :

• Healthy volunteers:
• Age: < 18 years
• Alcohol consumption less than 12 hours
• Person with co-morbidities such as chronic respiratory failure, type II diabetes, cancerous processes, chronic liver disease, chronic kidney disease
• Clinical signs of acute respiratory infection
• Persons who are unable to blow into exhaled-air analysis devices (in accordance with instructions for use)
• Persons under legal protection
• Pregnant women, women in labor or nursing mothers
• Persons deprived of their liberty by judicial or administrative decision
• Persons under psychiatric care
• Persons admitted to a health or social institution for purposes other than research
• Adults under legal protection (guardianship, curatorship)
• Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
• Patients with respiratory symptoms
• Age: < 18 years
• Patients whose symptoms have been present for more than 7 days
• Persons unable to blow into the device for breath analysis (in accordance with the operating instructions)
• Patients suffering from cystic fibrosis
• Patients with severe chronic respiratory insufficiency requiring long-term oxygen therapy or NIV (non-invasive ventilation), excluding CPAP (Continuous Positive Airway Pressure) for sleep apnea
• Patients under legal protection
• Pregnant women, women in labor or nursing mothers
• Persons deprived of their liberty by judicial or administrative decision
• Persons under psychiatric care
• Persons admitted to a health or social institution for purposes other than research
• Adults under legal protection (guardianship, curatorship)
• Persons not affiliated to a social security scheme or beneficiaries of a similar scheme

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 3 centers

• Emergency department (Hôpital de la Croix-Rousse, Hospices Civils de Lyon) Lyon (France) 6 — Lyon
• Maison de Santé Pluriprofessionnelle Universitaire (Hôpital de la Croix-Rousse, Hospices C — Lyon
• National reference center for respiratory viruses (Hôpital de la Croix-Rousse, Hospices Ci — Lyon

Identifiers

NCT: NCT07348380 · 69HCL25-0599 · 2025-A01542-47

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗