The Role of Volatile Organic Compounds (VOCs), Airway Mucins and the Microbiome in the Early Prediction of Bronchopulmonary Dysplasia (BPD)

NCT06342752 | Recruiting

• 1 other identifier: 6007
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Bronchopulmonary dysplasia (BPD), the most common respiratory complication of extremely preterm birth, significantly impacts healthcare with high morbidity and mortality rates. Despite the well-established primordial role of inflammation and oxidative stress in the development of BPD, clinical practice does not incorporate the testing for biomarkers associated with the development of BPD. The diagnosis of BPD based on required respiratory support at 36 weeks PML, stresses the need for an early prediction tool which could identify patients with high levels of these biomarkers. This on its turn, could also improve treatment approaches in clinical practice which are currently mostly supportive or non-specific and do not target underlying pathophysiologic pathways. Secondly, mucin expression aim to play a rol in other respiratory diseases, whereas in BPD only the potential role of MUC1 was explored. Thirdly, the composition of the airway microbial composition of an infant is assumed to be influenced by different factors. From early on in pregnancy the airway microbiome of the infant is formed, offering a protective role against pathologies. On the other hand, the role of the airway microbiome in the development of BPD remains unclear and needs to be elucidated. The threefold aim of this study is as follows: I. The development of a non-invasive breath test that allows early detection of bronchopulmonary dysplasia, using the potential of VOCs in exhaled breath as biomarkers for inflammation and oxidative stress. II. The exploration of the composition and diversity of the airway microbiome in infants with BPD, their association with exhaled VOCs and the exploration of the placental and vaginal microbiome. III. The detection of potential alterations in airway mucin expression in BPD patients. Through this comprehensive approach, we seek to gain a deeper understanding of how these mutual associations may contribute to the later development of BPD. In total 140 preterm infants, including 70 BPD patients and 70 preterm controls, born below 30 weeks' gestation at the Antwerp University Hospital will be included.

Conditions

Bronchopulmonary Dysplasia

Keywords

Volatile Organic Compounds; Preterm birth; Airway microbiome; Airway mucins; Exhaled breath analysis; Placental microbiome; Vaginal microbiome; Early prediction of BPD; Inflammation Lungs; Respiratory morbidity; multiple breath washout test

Outcome Measures

Primary Outcomes (6)

• Exhaled breath Volatile Organic Compounds (VOCs)

  Abbundance of VOCs in breath samples to distinguish BPD from preterm controls by means of GC-MS: direct samples in the respiratory circuit as well as indirect samples from air in the incubator

  first 4 weeks of life

• Vaginal microbiome

  Metagenomic shotgun sequencing after extraction of bacterial DNA from vaginal swabs after birth

  right before delivery

• Placental microbiome

  Metagenomic shotgun sequencing after extraction of bacterial DNA from samples and subamniotic swabs after birth

  at delivery

• Placental headspace VOCs

  Abbundance of VOCs in the headspace of placental samples to distinguish BPD from preterm controls

  at delivery

• Airway mucin profiles

  Genetic expression of airway mucins in BPD and preterm controls on oropharyngeal samples via qRT-PCR

  first 4 weeks of life

• Airway microbial profiles

  16S RNA sequencing or metagenomic shotgun sequencing after extraction of bacterial DNA from oropharyngeal swabs and aspirates in BPD and preterm controls

  12 months

Secondary Outcomes (5)

• Hypercapnia

  3 months

• Follow-up structural lung imaging

  12 months

• Pulmonary function

  12 months

• Chronic lung disease outcome 6 months corrected age

  6 months

• Chronic lung disease outcome 12 months corrected age

  12 months

Study Arms (2)

Preterm infants

all included infants will undergo a breath test and two throat swabs, in case the infant is intubated also endotracheal aspirates will be collected

Diagnostic Test: Breath test; Other: Throat swabs; Other: Endotracheal aspirates

Mothers of preterm infants

placental biopsies, a placental swab and a vaginal swab will be taken after birth

Other: Placental samples; Other: Vaginal swab

Interventions

Breath test DIAGNOSTIC_TEST

Early detection of volatile organic compounds (VOCs) in breath from preterm infants, collected at several timepoints within the first 4 weeks of life to predict BPD before diagnosis is made at 36 weeks PMA.

Also known as: Exhaled breath analysis, Volatomics, Exhaled Volatile Organic Compounds, Exhaled VOCs

Preterm infants

Throat swabs OTHER

A throat swab will be taken on several timepoints within the first 4 weeks of life to detect airway mucin expression. A second throat swab will be taken as proxy for the airway microbiome.

Preterm infants

Placental samples OTHER

After birth, placental biopsies will be collected for headspace VOCs analysis. A placental swab and a biopsy will be taken for microbiome analysis.

Also known as: Placental headspace VOCs analysis, Placental swabs

Mothers of preterm infants

Vaginal swab OTHER

A vaginal swab will be taken before birth for microbiome analysis.

Mothers of preterm infants

Endotracheal aspirates OTHER

Collection of aspirates, as part of routine care, to detect mucin expression and the lung microbiome.

Also known as: Aspirates

Preterm infants

Eligibility Criteria

• Age: 0 Days - 3 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Newborn infants born preterm \< 30 weeks gestational age at the Antwerp University Hospital and admitted to the neonatal intensive care unit.

You may qualify if:

• Born at a gestational age \< 30 weeks

You may not qualify if:

• Major congenital defect or disorder
• Patients with an unstable general condition as deemed by the attending neonatologist

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

University Hospital Antwerp

Edegem, Antwerp, 2650, Belgium

RECRUITING

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth; Pneumonia

Interventions

Breath Tests

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Antonius Mulder, MD, PhD,prof

  University Hospital Antwerp, Belgium

  PRINCIPAL INVESTIGATOR

• Stijn L Verhulst, MD, PhD,prof

  University Hospital Antwerp, Belgium

  STUDY DIRECTOR

Central Study Contacts

Inès Ghys, MD

CONTACT

+3232655230; ines.ghys@uantwerpen.be

Kristien Vanhaverbeke, MD, PhD

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: April 2, 2024
• Study Start: June 14, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)