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

NCT07352462 | Not Yet Recruiting

• 2 other identifiers: 69HCL25_06002025-A01544-45
• Study Type: interventional
• Target: 777
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

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

Keywords

Pandemic preparedness; Volatilome; Breath research; Respiratory infections; Diagnosis

Outcome Measures

Primary Outcomes (1)

• Description of the breath composition based on the area under each peak of exhaled air according to three levels of classification

  Levels of classification : * Patients with bacterial or viral respiratory infection vs. no respiratory infection (healthy subjects = control group) * Patients with viral vs. bacterial respiratory infection vs. undetermined respiratory infection vs. healthy subjects * Patients with respiratory infection due to Legionella spp vs another bacterium vs SARS-CoV-2 vs influenza vs another virus vs undetermined respiratory infection vs healthy subjects

  day one

Secondary Outcomes (11)

• Comparison of the overall properties of the test on exhaled air with the clinical classification of a severe respiratory infection used in practice. The test will therefore aim to differentiate patients with a respiratory infection who are hospitalized w

  Day one

• Differentiation of the three groups of participants-those with a viral respiratory infection, those with a bacterial respiratory infection, and healthy subjects-will be evaluated using the area under the curve (AUC), in order to assess the performance

  Day one

• Evaluation of viral load in respiratory samples will be performed by retesting all nasopharyngeal samples positive for an influenza virus, SARS-CoV-2, or Legionella. This criterion will correspond to the breath composition associated with viral load.

  Day one

• Description of the breath composition based on the AUC of each peak

  Day one

• Description of the breath composition based on the AUC of each peak

  Day one

Study Arms (4)

Bacterial respiratory infection

EXPERIMENTAL

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)

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

Viral respiratory infection

EXPERIMENTAL

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.

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

Undetermined respiratory infection

EXPERIMENTAL

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

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

Healthy patients

PLACEBO COMPARATOR

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.

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

Interventions

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

The collection and analysis of exhaled air for VOC detection is a non-invasive, painless procedure carried out offline. It can be summarised as follows: 1. Collection of 0.5-1 litre of exhaled air in a single-use Tedlar® bag 2. Transfer the exhaled air sample to a thermodesorption tube. The thermodesorption tube will be sent to the laboratory responsible for the analysis within 1-5 days of collection. 3. The breath sample will be analysed in the laboratory using thermal desorption-GC/MS. 4. Processing of the raw data to determine the chemical composition of VOCs and identify the compounds present in the exhaled air sample. 5. Statistical analysis of all generated data will be performed to identify interesting VOC profiles.

Bacterial respiratory infection; Healthy patients; Undetermined respiratory infection; Viral respiratory infection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (7)

Emergency department (Hôpital de la Croix-Rousse, Hospices Civils de Lyon)

Lyon, 69004, France

Location

Infectious Disease Service of Hôpital de la Croix-Rousse (Hospices Civils de Lyon)

Lyon, 69004, France

Location

Intensive Care Unit of Hôpital de la Croix-Rousse (Hospices Civils de Lyon)

Lyon, 69004, France

Location

Intensive Care Unit of Hôpital Lyon Sud (Hospices Civils de Lyon)

Lyon, 69004, France

Location

Internal Medecine Unit of Hôpital de la Croix-Rousse (Hospices Civils de Lyon)

Lyon, 69004, France

Location

National reference center for respiratory viruses (Hôpital de la Croix-Rousse, Hospices Civils de Lyon)

Lyon, 69004, France

Location

Pneumology Unit of Hôpital de la Croix-Rousse (Hospices Civils de Lyon)

Lyon, 69004, France

Location

MeSH Terms

Conditions

Respiratory Tract Infections; COVID-19; Legionnaires' Disease; Disease

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Legionellosis; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr Alexandre GAYMARD

CONTACT

+4 72 07 10 53; alexandre.gaymard@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a cross-sectional diagnostic study using case-control sampling, where the number of cases and non-cases is fixed in advance, and a gold standard comparison is used. 0

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: January 20, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): February 3, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)