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

NCT ID: NCT06342752

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 140 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-14
• Study Completion Date: 2027-09-30

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.

Detailed Description

After birth, a swab and samples will be collected from the placenta, next to a maternal vaginal swab for microbiome analysis. Breath samples, two oropharyngeal swabs and endotracheal aspirates - in case intubated - will be collected from the infant on different days in the first 28 days of life.

At 36 weeks PMA, BPD is diagnosed if the infant still requires respiratory support. An oxygen reduction test will also be performed to determine if the infant can maintain saturations within a predetermined target range (90-96% in our hospital) during a stepwise reduction of oxygen, while closely monitoring the neonate. At 36 weeks PMA, infants diagnosed with BPD - as well as controls - will undergo a one-time capillary (or venous) blood gas test, which will be mostly done as part of routine care. The blood gas test will be combined with a continuous transcutaneous capnography (tcPCO2) for 24 hours to assess the degree of severity of lung damage, i.e. grade of alveolar hypoventilation by means of hypercapnia.

All enrolled participants, regardless of BPD diagnosis, will have two clinical follow-up study visits after discharge to home, at 6 and at 12 months corrected age. Another oropharyngeal swab will be collected at these visits for microbiome analysis. To assess lung function in all BPD patients, a multiple breath washout test during natural sleep after the administration of melatonin, will be performed at 6 and 12 months corrected age. At 6 and 12 months corrected age, a chest CT will be performed in severe BPD-cases to assess lung structure. Results of follow-up investigations, clinical data, as well as respiratory questionnaires will be used to correlate to findings of the analysis of all samples taken in the NICU. With this approach, it is not only possible to explore if possible biomarkers found in the early weeks of life could predict BPD at 36 weeks PML, but also respiratory/pulmonary outcome at 6 and 12 months corrected age.

Conditions

Bronchopulmonary Dysplasia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Breath test

Intervention Type: 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.

Throat swabs

Intervention Type: 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.

Endotracheal aspirates

Intervention Type: OTHER

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

Mothers of preterm infants

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

Placental samples

Intervention Type: OTHER

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

Vaginal swab

Intervention Type: OTHER

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

Interventions

Breath 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.

Intervention Type: DIAGNOSTIC_TEST

Throat swabs

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.

Intervention Type: OTHER

Placental samples

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

Intervention Type: OTHER

Vaginal swab

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

Intervention Type: OTHER

Endotracheal aspirates

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

Intervention Type: OTHER

Other Intervention Names

Exhaled breath analysis; Volatomics; Exhaled Volatile Organic Compounds; Exhaled VOCs; Placental headspace VOCs analysis; Placental swabs; Aspirates

Eligibility Criteria

Inclusion Criteria

• Born at a gestational age < 30 weeks

Exclusion Criteria

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

• Minimum Eligible Age: 0 Days
• Maximum Eligible Age: 3 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonius Mulder, MD, PhD,prof

Role: PRINCIPAL_INVESTIGATOR

University Hospital Antwerp, Belgium

Stijn L Verhulst, MD, PhD,prof

Role: STUDY_DIRECTOR

University Hospital Antwerp, Belgium

Locations

University Hospital Antwerp

Edegem, Antwerp, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Inès Ghys, MD

Role: CONTACT

ines.ghys@uantwerpen.be

+3232655230

Kristien Vanhaverbeke, MD, PhD

Role: CONTACT

Facility Contacts

Inès Ghys

Role: primary

ines.ghys@uantwerpen.be

Other Identifiers

6007

Identifier Type: -

Identifier Source: org_study_id