Volatile Organic Compounds Analysis by GC-MS for Diagnostic of Hospitalised Patients With Respiratory Infections Using Exhaled Breath (VORTEX-2)

Civil Hospices of Lyon

Status: Not yet enrolling

Conditions: COVID-19; Respiratory Infections; Influenza Virus Infection; Legionella Pneumophila Infections

Treatments: Device: Volatile Organic compounds (VOC) analysis in Exhaled breath using GC-MS

Study type: Interventional

Funder types: Other

Identifiers

NCT07352462

2025-A01544-45 (Other Identifier)

69HCL25_0600

Details and patient eligibility

About

Emerging respiratory diseases represent a global threat. Viruses such as influenza and coronaviruses have been the main drivers of pandemics over the past century. More broadly, the impact of these respiratory infections is not limited to pandemic risks. Indeed, some of them also trigger seasonal epidemics with a significant medical and economic burden. Consequently, it is essential to strengthen global surveillance, and diagnostic capacities for the pathogens responsible for respiratory infections.

The diagnosis of respiratory infections is even more important in cases of severe infection, as it helps guide and adapt patient management according to the responsible pathogen.

A promising and well-recognized approach is the analysis of exhaled breath, 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, and can be disrupted by the presence of a pathogen.

A parallel clinical study, VORTEX-1, aims to establish the performance of breath analysis for the diagnosis of respiratory infections in the context of the general population, or patient triage in emergency wards. This study targets patients with non-severe respiratory infections, mostly caused by viral pathogens.

Thanks to a specific technique, the VORTEX-1 study will make it possible to test a direct on-site sampling and analysis process, painless and with real-time chemical detection.

This methodology, highly suited to triage situations, remains difficult to apply in the case of respiratory infections requiring hospitalization. Indeed, hospitalized patients are usually admitted to different units depending on their clinical status, risk factors, or bed availability. This diversity of settings makes it impossible to implement a process that depends on an instrument which cannot be available or moved in real time across all units. To address this challenge, the investigators will use an alternative method.

In the VORTEX-2 trial, samples of exhaled gases will be collected directly at the patient's bedside using a single-use device for breath collection. The samples will then be transferred to a laboratory for analysis. This approach is more suitable for severe respiratory infections.

To be as comprehensive as possible in the study of the volatilome in the context of respiratory infections, it is important to include hospitalized patients and to develop a system that can also be implemented in routine clinical practice.

The link between the two studies (VORTEX-1 and VORTEX-2) will be established through a "control" group, consisting of healthy subjects (without respiratory infections or severe/chronic diseases), whose breath will be collected using both approaches.

Enrollment: 777 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years old
• Having signed a written informed consent
• Presenting a NEWS-2 score of 5 (>4) or one of the individual score criteria rated 3
• Hospitalized in one of the HCL (Hospices Civils de Lyon) departments participating in the study
• 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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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777 participants in 4 patient groups, including a placebo group

Bacterial respiratory infection

Experimental group

Description:

To classify patients, an adjudication committee will base its decision on a range of clinical and biological factors: * The ICD-10 code (International Classification of Diseases, 10th revision) assigned to the patient during their treatment * Radiological examination indicating bacterial pneumonia (community-acquired pneumonia or CAP) * Biological results: * Microbiological diagnostic tools (RT-PCR tests, culture) indicating a bacterial infection. * Procalcitonin measurement (indicating a bacterial infection if \> 0.1 µg/L)

Treatment:

Device: Volatile Organic compounds (VOC) analysis in Exhaled breath using GC-MS

Viral respiratory infection

Experimental group

Description:

To classify patients, an adjudication committee will base its decision on a range of clinical and biological factors: * The ICD-10 code (International Classification of Diseases, 10th revision) assigned to the patient during their treatment * Radiological examination not indicating bacterial pneumonia * Biological results: * Microbiological diagnostic tools (RT-PCR tests, culture) indicating a viral infection. For example, respiratory infections will be attributed to a virus if at least one of the diagnostic tests used is positive for a virus or if the interferon test shows a very high score.

Treatment:

Device: Volatile Organic compounds (VOC) analysis in Exhaled breath using GC-MS

Undetermined respiratory infection

Experimental group

Description:

All patients who matched the inclusion criteria and could not be classified into groups 1 or 2 by an adjudication committee.

Treatment:

Device: Volatile Organic compounds (VOC) analysis in Exhaled breath using GC-MS

Healthy patients

Placebo Comparator group

Description:

The group of healthy volunteers, serving as the control group, will be composed of adult subjects with no respiratory symptoms or known acute or chronic pathology at the time of inclusion. They will be sampled using the same methods as the other groups in order to enable a reliable comparison of the metabolic signatures obtained.

Treatment:

Device: Volatile Organic compounds (VOC) analysis in Exhaled breath using GC-MS