Clinical trial NCT06342752: The Role of Volatile Organic Compounds (VOCs), Airway Mucins and the Microbiome in the Early Prediction of Bronchopulmonary Dysplasia (BPD)
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 140
Sex: ALL
Minimum age (years): 0
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Exhaled breath Volatile Organic Compounds (VOCs)
timeFrame: first 4 weeks of life
measure: Vaginal microbiome
timeFrame: right before delivery
measure: Placental microbiome
timeFrame: at delivery
measure: Placental headspace VOCs
timeFrame: at delivery
measure: Airway mucin profiles
timeFrame: first 4 weeks of life
measure: Airway microbial profiles
timeFrame: 12 months
Secondary outcomes:
measure: Hypercapnia
timeFrame: 3 months
measure: Follow-up structural lung imaging
timeFrame: 12 months
measure: Pulmonary function
timeFrame: 12 months
measure: Chronic lung disease outcome 6 months corrected age
timeFrame: 6 months
measure: Chronic lung disease outcome 12 months corrected age
timeFrame: 12 months
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: University Hospital Antwerp
state: Antwerp
Study officials:
affiliation: University Hospital Antwerp, Belgium
name: Antonius Mulder, MD, PhD,prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Antwerp, Belgium
name: Stijn L Verhulst, MD, PhD,prof
role: STUDY_DIRECTOR
References: