Clinical trial NCT06140901: Bronchial Epithelium of Children With Post-infectious Bronchiolitis Obliterans
Official title: Morphological and Functional Pilot Study of the Bronchial Epithelium of Children With Post-infectious Bronchiolitis Obliterans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bronchiolitis Obliterans
Keywords: children
post infectious
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2023-11-21
Enrollment: 450
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The main objective is to define damage to the respiratory epithelium in children with PIBO following an Adenovirus (ADV) or Rhinovirus (RV) infection.
timeFrame: through study completion, an average of 3 year
Secondary outcomes:
measure: 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.
timeFrame: through study completion, an average of 3 year
measure: 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.
timeFrame: through study completion, an average of 3 year
measure: Describing the transcriptomic profile of bronchial biopsies from children with PIBO.
timeFrame: through study completion, an average of 3 year
measure: Following the morphology of the nasal and bronchial epithelia of PIBO over the course of the disease
timeFrame: through study completion, an average of 3 year
Other outcomes:
Locations:
city: Marseille
country: France
facility: APHM
Study officials:
affiliation: APHP Marseille
name: Julie MAZENQ, PhD
role: PRINCIPAL_INVESTIGATOR
References: