Exhaled Breath Analysis by Secondary Electrospray Ionization - Mass Spectrometry in Children and Adolescents

Official title

Exhaled Breath Analysis by Secondary Electrospray Ionization - Mass Spectrometry in Children and Adolescents (EBECA)

Overview

This study is to investigate breath analysis (breath metabolomics) combined with established bioinformatic tools as a platform for companion diagnostics.

Detailed description

Therapeutic drug monitoring (TDM) is defined as measuring concentrations of a drug at one or more time points in a biological matrix after a dose. The purpose of TDM is to individualize the drug dose to achieve maximum efficacy and at the same time minimize toxicity. The concept of TDM could potentially be even more valuable if in addition to drug concentrations, other drug-regulated and drug-related metabolites could be included in the models to define optimal dosage. There exists a clinical need to stratify patients with better precision to improve current clinical and therapeutic management. Breath analysis offers an opportunity to non-invasively retrieve relevant information on the ongoing internal biochemical processes, as well as to monitor the respiratory system itself. For breath analysis, a Secondary Electrospray ionization - mass spectrometry (SESI-MS) breath analysis platform will be used to capture disease-related, drug-regulated and drug-related metabolites (breath metabolomics) in exhaled breath. This information, retrieved in parallel to standard of care clinical co-variates, could have the potential to provide a more personalized therapeutic management of patients.

Interventions

• Diagnostic test Real-time SESI-MS breath analysis
  Participants will be asked to refrain from eating, drinking, chewing gum use or brushing their teeth at least 1 hour before the measurements will be performed. Room temperature and lighting will be set at the same level for all measurements. Participants will exhale through a disposable mouthpiece into a commercially available SESI source (FIT S.L., Spain). While performing full exhalations, the subjects will keep the pressure through the sampling line at a fixed value monitored by a digital man
• Diagnostic test Off-line breath analysis
  In young children below the age of 4 not capable of completing the on-line exhalation maneuvers, or in cases when the patient needs cannot approach the mass spectrometer, the sample will be collected off-line. They will be asked to exhale into a bag that will be transported to the lab and deflated into the mass spectrometer for analysis. Exhaled breath of patients under anesthesia will also collected using available ventilation system in the operation theatre.
• Diagnostic test Blood analysis
  Blood analysis done in patients who undergo regular blood sampling needed for clinical routine laboratory controls. This includes i) children and adolescents receiving medications which require TDM ii) patients with acute diseases such as TD1 and pneumonia and iii) patients with chronic diseases such as asthma bronchiale. For those patients where a blood sample is drawn during the clinical routine, an additional blood sample consisting of only several blood drops will be collected using the same
• Diagnostic test Saliva analysis
  During the diagnostic and therapeutic work-up of T1D patients, saliva samples are collected during the clinical routine. For those patients, additional samples will be obtained by clinically trained investigators.
• Diagnostic test Urine analysis
  During the diagnostic and therapeutic work-up of T1D patients, urine samples are collected during the clinical routine. For those patients, additional samples will be obtained by clinically trained investigators.

Primary outcome measures

• Days of hospitalization [Time frame: approx 30 days (from beginn hospitalisation to discharge date)]
• Change in Mass spectrometric profile of exhaled breath patterns [Time frame: Week 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)]
• Change in Concentration of exhaled metabolites of pharmacotherapy [Time frame: Week 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)]

Secondary outcome measures (5)

• Identification of chemical structure of exhaled molecules (acetone, glucose) [Time frame: approx 30 days (from begin hospitalisation to discharge date)]
• Correlations of identified molecules (acetone, glucose) in exhaled breath with body fluids (blood, saliva, urine) for T1D acute disease (mmol/l) [Time frame: 0h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h, 72h (h =hours after hospital admission)]
• Change in clinical endpoint lung function (Forced Expiratory Pressure in 1 Second FEV1 l/s) for correlation between clinical endpoint and the abundance of exhaled metabolites [Time frame: approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)]
• Change in clinical endpoint (body temperature, Celsius) for correlation between clinical endpoint and the abundance of exhaled metabolites [Time frame: approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)]
• Change in clinical endpoint (blood pressure, mmHg) for correlation between clinical endpoint and the abundance of exhaled metabolites [Time frame: approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)]

Eligibility criteria

Inclusion criteria

• Age 0 ≤ 22 years at study entry and signed informed consent

Additional inclusion criteria for respiratory disease population:

• Acute disease: - Acute signs for a respiratory disease, indicated by e.g. increased work of breathing (e.g. dyspnea, increased respiratory rate), cough or wheezing.
• Chronic disease: - Suspected or confirmed chronic airway disease (e.g. asthma).

Additional inclusion criteria for neurological disease population:

• Acute disease: - Acute presentation or report within 24 hours of any signs of neurological deficit (motor function, sensoneural, or verbal).
• Chronic disease: - Confirmed chronic neurologic disease (e.g. childhood epilepsy).

Additional inclusion criteria for T1D disease population:

• Acute disease: - Hyperglycemia and/or pH (venous) <7.3, bicarbonate >10 mmol/L, increased levels of acetone in blood or urine in the context of newly diagnosed or known T1D.
• Chronic disease: - Confirmed diagnosis of T1D

Exclusion criteria

• Physical or intellectual impairment precluding protocol adherence.

Additional exclusion criteria for respiratory disease population:

• Known malignancy, active smoker (passive smoke exposure is not an exclusion criterium), known inflammatory diseases (e.g. autoimmune disease) that require medical and/or pharmacological treatment and is associated with an inflammatory response, relevant congenital defects

Additional exclusion criteria for neurological disease population:

• Known malignancy, active smoker (passive smoke exposure is not an exclusion criterium), known inflammatory diseases (e.g. autoimmune disease) that require medical and/or pharmacological treatment and is associated with an inflammatory response, relevant congenital defects.

Additional exclusion criteria for T1D population:

• Known malignancy, active smoker (passive smoke exposure is not an exclusion criterium), relevant congenital defects.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Switzerland · 1 center

• University Children's Hospital Basel (UKBB) — Basel

Publications

• Zeng J, Stankovic N, Singh KD, Steiner R, Frey U, Erb T, Sinues P. Breath Analysis of Propofol and Associated Metabolic Signatures: A Pilot Study Using Secondary Electrospray Ionization-High-resolution Mass Spectrometry. Anesthesiology. 2025 Aug 1;143(2):345-356. doi: 10.1097/ALN.0000000000005531. Epub 2025 Apr 21. PMID 40258137

Identifiers

NCT: NCT04461821 · 2020-00778; ks20Sinues

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗