Viral Infections and Airway Microbiome in Young Children With Cystic Fibrosis

Respiratory Viral Infection Clinical Trial

Official title:

The Interaction Between Viral Infections and the Development of the Airway Microbiome in Young Children With Cystic Fibrosis

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06188988
• Other study ID #: 5812
• Status: Enrolling by invitation
• Start date: November 1, 2023
• Est. completion date: October 31, 2025

Study information

• Verified date: November 2023
• Source: University Hospital, Antwerp
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Cystic fibrosis (CF) is the most common hereditary life-threatening condition in Belgium. Because of a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel, chloride is unable to move to the cell surface and mucus becomes more viscous. Consequently, CF patients are not able to clear their lungs efficiently, and trapped bacteria can lead to chronic infection and inflammation of the lungs, and ultimately respiratory failure.

CF lung disease starts at birth due to muco-inflammatory processes and is associated with a significantly altered microbial colonization of the infant airways compared to infants without CF. Additionally, young children with CF suffer from viral infections as often as their healthy peers, but the episodes are more severe and often prolonged. Moreover, frequent viral infections in children with CF contribute towards a more pathogenic airway microbiome at a young age. Although this link has been previously reported, the exact mechanisms by which this occurs need to be elucidated.

A pulmonary exacerbation in CF is characterized by an increase in respiratory symptoms, general symptoms and a decline in lung function. Most young children with CF suffer from a mean of 4 exacerbations per year for which antibiotics are prescribed. Despite the current novel therapies in CF, treatment of respiratory infections stay relevant and is a greater challenge with increasing survival.

The key objective of this study is to gain insights into the mechanisms by which viral infections leading to pulmonary exacerbations induce a more pathogenic microbiome in young children with CF.

About forty participants will be recruited at the paediatric CF clinic of the Antwerp University Hospital. Inclusion criteria are an age of less than 5 years and a diagnosis of CF. There are no exclusion criteria. Duration of the study is 1 year to cover for seasonality of clinical symptoms. Study visits are scheduled at 3-month intervals corresponding with the regular follow up, or unscheduled during an acute pulmonary exacerbation. From all participants, two oropharyngeal swabs (for microbiome analysis and for immunological/mucin analysis) will be collected at set time points. For the linking of the laboratory data to the clinical characteristics, we will examine demographics, environmental exposures, and disease markers of CF. Next to the collection of the oropharyngeal swabs, a history, physical examination, and technical investigations will be performed at the study visits.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 40
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 5 Years

Eligibility

Inclusion Criteria:

• Diagnosis of cystic fibrosis

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Cystic Fibrosis
• Cystic Fibrosis in Children
• Fibrosis
• Infections
• Inflammation
• Pneumonia
• Respiratory Morbidity
• Respiratory Viral Infection
• Virus Diseases

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Antwerp

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	airway microbial profiles of young cystic fibrosis patients	Metagenomic shotgun sequencing after extraction of bacterial DNA from oropharyngeal swabs	1 year
Primary	airway inflammatory profiles of young cystic fibrosis patients	cytokine levels in oropharyngeal swabs, measured by multiplex ELISA	1 year
Primary	Airway mucin profiles of young cystic fibrosis patients	mucin profiles in oropharyngeal samples via qRT-PCR	1 year
Primary	Demographic data of young cystic fibrosis patients	Age (in years), CFTR genotype (description of mutation), Sex (male/female), ethnicity (hispanic or latino/not hispanic or latino), race (american indian or alaska native/asian/black or african american/native hawaiian or other pacific islander/white)	1 year
Primary	Environmental data in young cystic fibrosis patients	Mode of birth delivery (vaginal delivery / caesarian section), birth weight (in kg), feeds in infancy (breastfeeding exclusively/breastfeeding in combination with formula/exclusively formula feeding), smoke exposure (prenatal/postnatal/ongoing), day care (Yes/No), vaccinations (according to schedule/not according to schedule), physical activity (Yes/No), parent education (mother normal or low level, father normal or low level), household income (normal/low level), postcode (number), rural living (yes/no), urban living (Yes/no), season of sampling (spring/summer/autumn/winter), type of medication (name), duration of medication (in weeks), type of antibiotics for pulmonary exacerbation (name), duration time of antibiotics for pumonary exacerbation (in weeks)	1 year
Primary	Disease markers of young cystic fibrosis patients	RR (in /min), SpO2 ( in %), BMI (in kg/m2), temperature (in °C), rhinosinusitis (yes/no), nasal congestion (yes/no), acute otitis media (yes/no), fever (yes/no), decreased activity level (yes/no), dyspnea (Yes/no), cough (Yes/no), sputum production (yes/no), wheezing (yes/no), crackles (yes/no), differential air entry (yes/no), bronchiolitis (yes/no), pneumonia (yes/no), pulmonary exacerbation (yes/no), CFQ-R score, lung function FEV1 (Z-score), lung function LCI (Z-score), bronchiectasis on CT scan (yes/no), wall thichening on CT scan (Yes/no), mucous plugging on CT scan (yes/no), air trapping on CT scan (Yes/No), previously or new relevant (extra)pulmonary conditions/illnesses (name of diagnoses)	1 year
Secondary	Virome profiling in young cystic fibrosis patients during an acute pulmonary exacerbation	Extensive profiling of viruses in young cystic fibrosis patients after taking orpharyngeal sample during an acute pulmonary exacerbation by multiplex qPCR.	1 month