Bronchial Epithelium of Children With Post-infectious Bronchiolitis Obliterans

NCT06140901 | Recruiting

• 2 other identifiers: C23-372023-A01544-41
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bronchiolitis Obliterans

Keywords

children; post infectious

Outcome Measures

Primary Outcomes (1)

• The main objective is to define damage to the respiratory epithelium in children with PIBO following an Adenovirus (ADV) or Rhinovirus (RV) infection.

  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 Outcomes (4)

• 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.

  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.

  through study completion, an average of 3 year

• Describing the transcriptomic profile of bronchial biopsies from children with PIBO.

  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

  through study completion, an average of 3 year

Study Arms (2)

Arm non PIBO

ACTIVE COMPARATOR

children hospitalized for adenovirus or rhinovirus infection with non progressing to PIBO

Diagnostic Test: Study morphological and functional of respiratory epithelium

Arm PIBO

ACTIVE COMPARATOR

Children hospitalized for adenovirus or rhinovirus infection with progressing to PIBO in evolution.

Diagnostic Test: Study morphological and functional of respiratory epithelium

Interventions

Study morphological and functional of respiratory epithelium DIAGNOSTIC_TEST

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.

Arm PIBO; Arm non PIBO

Eligibility Criteria

• Age: 1 Month - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• The existence of an underlying chronic pulmonary pathology (e.g. cystic fibrosis, ciliary dyskinesia).
• A coagulation pathology.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

APHM

Marseille, 13000, France

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Study Officials

• Julie MAZENQ, PhD

  APHP Marseille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie MAZENQ, PhD

CONTACT

0491386808; julie.mazenq@ap-hm.fr

Delphine Gras

CONTACT

delphine.gras@univ-amu.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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. After inclusion of the patients, a second nasal swab will be taken as part of the research for the PCR study of the subtypes of the virus responsible for the viral infection. Following the diagnosis of PIBO, bronchial endoscopy for microbiology and bronchial biopsies will be performed as part of routine care to rule out differential diagnoses. During this endoscopy, 2 additional bronchial biopsies and nasal brushing for research will be performed to recover epithelial cells.

Study Record Dates

• First Submitted: October 27, 2023
• First Posted: November 21, 2023
• Study Start: December 4, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

FR (1)