The Role of VOCs, Airway Mucins and Airway Microbiome in Bronchopulmonary Dysplasia

Bronchopulmonary Dysplasia Clinical Trial

— INFANCY  

Official title:

The Role of Volatile Organic Compounds (VOCs), Airway Mucins and Microbiome in the Development of Bronchopulmonary Dysplasia and the Feasibility of Exhaled Breath VOCs Analysis as an Early Detection Tool

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06342752
• Other study ID #: 6007
• Status: Not yet recruiting
• Start date: April 2024
• Est. completion date: September 2027

Study information

• Verified date: March 2024
• Source: University Hospital, Antwerp
• Contact: Inès Ghys, MD
• Phone: +32 3 265 26 32
• Email: ines.ghys[@]uantwerpen.be
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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. Infants diagnosed with BPD will undergo a one-time capillary (or venous) blood gas test 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 months corrected age, a chest CT will be performed in severe BPD-cases to assess lung structure.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: September 2027
• Est. primary completion date: September 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Days to 3 Days

Eligibility

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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia

Intervention

Diagnostic Test:
• 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.

Other:
• 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.
• 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.
• Vaginal swab
A vaginal swab will be taken before birth for microbiome analysis.
• Endotracheal aspirates
Collection of aspirates, as part of routine care, to detect mucin expression and the lung microbiome.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Antwerp

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exhaled breath Volatile Organic Compounds (VOCs)	Abbundance of VOCs in breath samples to distinguish BPD from preterm controls by means of GC-MS	first 4 weeks of life
Primary	Airway mucin profiles	Genetic expression of airway mucins in BPD and preterm controls on oropharyngeal samples via qRT-PCR	first 4 weeks of life
Primary	Airway microbial profiles	Metagenomic shotgun sequencing after extraction of bacterial DNA from oropharyngeal swabs in BPD and preterm controls	first 4 weeks of life
Secondary	Placental headspace VOCs	Abbundance of VOCs in the headspace of placental samples to distinguish BPD from preterm controls	at delivery
Secondary	Placental microbiome	Metagenomic shotgun sequencing after extraction of bacterial DNA from samples and subamniotic swabs after birth	at delivery
Secondary	Vaginal microbiome	Metagenomic shotgun sequencing after extraction of bacterial DNA from vaginal swabs after birth	right before delivery
Secondary	Follow-up structural lung imaging	Chest CT scan in severe BPD cases	9 months
Secondary	Hypercapnia	BPD patients will undergo a blood gas test to assess the degree of lung damage severity	3 months