Bronchial Epithelium of Children With Post-infectious Bronchiolitis Obliterans (e-PIBO)

April 23, 2025 updated by: Institut National de la Santé Et de la Recherche Médicale, France

Morphological and Functional Pilot Study of the Bronchial Epithelium of Children With Post-infectious Bronchiolitis Obliterans

Bronchiolitis obliterans (BO) is an irreversible chronic obstructive pulmonary pathology leading to obstruction and/or obliteration of the small airways. In children, the most common form of BO occurs following a serious lower respiratory tract infection. This is a rare complication; the incidence is unknown. The diagnosis, often late, is made on clinical, spirometric and radiological arguments. The pathophysiology would be linked to damage to the airway epithelium. PIBO is most commonly associated with adenovirus (ADV) infection (serotypes 3, 7, 11 and 21) but also other viruses such as rhinovirus (RV). The treatment of PIBO is not clearly established, it remains empirical.

The research hypothesis is that the morphology of the nasal epithelium of children with ADV or RV infection is different for those progressing to PIBO. The main objective of the proposed observational study is to characterize damage to the respiratory epithelium in these children.

This is a single-center prospective longitudinal study (AP-HM), in children aged 1 month to 6 years, comparing children hospitalized for lower respiratory infection by ADV or RV progressing or not to PIBO. All children included will have a nasal swab and brushing on D0. Children developing PIBO will have nasal brushing with bronchial endoscopy with bronchial biopsies and bronchoalveolar washing at the time of PIBO diagnosis and again at M6 in case of partial response to treatment.

This is therefore a pilot study aimed at defining damage to the respiratory epithelium in children with PIBO following an ADV or RV infection and the role of respiratory epithelial cells in PIBO.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Children from 1 month to 6 years hospitalized at the Timone Enfant University Hospital
  2. Diagnosis of an adenovirus or rhinovirus respiratory infection confirmed on a nasal swab, made upon arrival as part of the child's initial care
  3. Consent form read, understood, approved and signed by parents before any study procedure
  4. Affiliation to a social security scheme or beneficiary of such a scheme

The inclusion criteria for children who were not hospitalized when diagnosed with an adenovirus and rhinovirus respiratory infection at the Timone Enfant University Hospital are:

  1. Children from 1 month to 6 years old transferred to the Timone Enfant University Hospital

  2. Show the following signs:

    has. Clinical: clinical signs persist 6 weeks after a viral infection: tachypnea, wheezing and/or persistent hypoxemia b. Scan: mosaic appearance +/- bronchiectasis, atelectasis vs. +/- EFR if performed: obstructive ventilatory disorder not or only slightly reversible after bronchodilators

  3. Consent form read, understood, approved and signed by parents before any study procedure
  4. Affiliation to a social security scheme or beneficiary of such a scheme

Exclusion Criteria:

  1. Refusal of participation in the study by the family will be a reason for non-inclusion, as well as in the absence of parental authority.
  2. The existence of an underlying chronic pulmonary pathology (e.g. cystic fibrosis, ciliary dyskinesia).
  3. A coagulation pathology.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm non PIBO
children hospitalized for adenovirus or rhinovirus infection with non progressing to PIBO
Diagnostic test: Study morphological and functional of respiratory epithelium
The working's investigators hypothesis is that the morphology and functional of the epithelium of children with ADV or RV respiratory infection is different between those who progress to PIBO and those who do not.
Active Comparator: Arm PIBO
Children hospitalized for adenovirus or rhinovirus infection with progressing to PIBO in evolution.
Diagnostic test: Study morphological and functional of respiratory epithelium
The working's investigators hypothesis is that the morphology and functional of the epithelium of children with ADV or RV respiratory infection is different between those who progress to PIBO and those who do not.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The main objective is to define damage to the respiratory epithelium in children with PIBO following an Adenovirus (ADV) or Rhinovirus (RV) infection.
Time Frame: through study completion, an average of 3 year
The morphology of the nasal and bronchial epithelia of PIBO will be analysed during the course of the disease both ex vivo and in vitro. Several criteria will be analysed, such as cell composition, thickness and epithelial cohesion during the culture of reconstituted nasal and/or bronchial epithelium, using microscopy.
through study completion, an average of 3 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Looking for pro-inflammatory and antiviral mediators involved in remodelling and epithelial-mesenchymal transition or that may be involved in the development of a PIBO.
Time Frame: through study completion, an average of 3 year
Dosage pro-inflammatory and antiviral mediators involved in remodeling and epithelial-mesenchymal transition. Level of expression of adenovirus and rhinovirus receptor: CAR, CD46, ICAM-1.
through study completion, an average of 3 year
Describing the transcriptomic profile of bronchial biopsies from children with PIBO.
Time Frame: through study completion, an average of 3 year
An analysis of the transcriptome at the single-cell level will highlight the cellular heterogeneity of bronchial biopsies from children with OPDP, identify rare cell sub-populations and monitor the dynamics of cell evolution during development or as a function of its environment (cell interactions, pathogens, treatments, etc) by comparing them with databases of 'control' biopsies (FasteQ, Hu-man cell lungatlas).
through study completion, an average of 3 year
Following the morphology of the nasal and bronchial epithelia of PIBO over the course of the disease
Time Frame: through study completion, an average of 3 year
Quantifying the production of pro-inflammatory mediators matory with alarmins (TSLP, IL-33 and IL-25), IL-6 and IL-8) and antivirals (IFN types I and III) with ELISA and western blot, involved in remodeling and epithelial-mesenchymal transition (FGF, EGF, TGF-alpha).
through study completion, an average of 3 year
Evaluating the response of the nasal epithelium to viral stimulation in children with and without PIBO and those who had not developed PIBO after respiratory infection with ADV and/or RV.
Time Frame: through study completion, an average of 3 year

Quantifying the production of pro-inflammatory mediators with alarmins (TSLP, IL-33 and IL-25), cytokines (IL-6 and IL-8) and antivirals (IFN types I and III).

TSLP, IL-33, IL-25, IL-6 and IL-8, IFN types I and III will have the same units of measure.

Assay of PANoptosis markers with apoptosis, pyroptosis and necroptosis: caspase, GSDMD, MKL.
through study completion, an average of 3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Julie MAZENQ, PhD, APHP Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2023

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

October 27, 2023

First Submitted That Met QC Criteria

November 14, 2023

First Posted (Actual)

November 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 25, 2025

Last Update Submitted That Met QC Criteria

April 23, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C23-37
  • 2023-A01544-41 (Other Identifier: IDRCB Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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