Functional Analysis by Dynamic Imaging of the Respiratory Epithelium in Infants with Cystic Fibrosis

Analyse Fonctionnelle Par Imagerie Dynamique De L'épithélium Respiratoire Chez Des Nourrissons Atteints De Mucoviscidose

Cystic fibrosis (CF) is characterized by airway inflammation and infection leading to progressive destruction of lungs. One of the most important abnormalities in CF is an abnormal processing of the mutated CFTR protein through the endoplasmic reticulum that causes abnormal location or even absence of the protein at the apical plasma membrane of airway epithelial cells. This abnormality results in a marked dehydration of the airway surface fluid, decreased mucus transport and airway obstruction. Nevertheless, the events that occur very early during the progression of the disease at the airway level in infants are not known. At cellular level, it has also been reported that the CFTR expression and localization could be related to the differentiation state of the airway epithelium. Furthermore, it has been reported that gap junctions could be involved in dysregulate inflammation process. In CF infants, many answers are still lacking. For a better understanding of the early stages of cystic fibrosis, it is of major interest to study respiratory epithelial cells obtained as early as possible. In 15 CF infants and 15 control infants, a nasal brushing will be performed by means of a soft sterile cytology brush. Samples will be used for cytological and functional studies: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities. These studies will be done in basal conditions and will be repeated after activation of the nasal epithelial cells by the bacteria, such as Staphylococcus aureus, which can be found very early in the course of CF disease.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Procedure: A nasal brushing

Detailed Description

Cystic fibrosis (CF) is characterized by airway inflammation and infection leading to progressive destruction of lungs. One of the most important abnormalities in CF is an abnormal processing of the mutated CFTR protein through the endoplasmic reticulum that causes abnormal location or even absence of the protein at the apical plasma membrane of airway epithelial cells. This abnormality results in a marked dehydration of the airway surface fluid, decreased mucus transport and airway obstruction. Nevertheless, the events that occur very early during the progression of the disease at the airway level in infants are not known. At cellular level, it has also been reported that the CFTR expression and localization could be related to the differentiation state of the airway epithelium. Furthermore, it has been reported that gap junctions could be involved in dysregulate inflammation process. In CF infants, many answers are still lacking.

Is inflammation present before infection? Is native epithelium of CF infants more sensitive than controls? Could the investigators analyse the localisation and functionality of CFTR, tight and gap junctions in respiratory epithelial cells in CF infants? Could the activation of the epithelial cells by bacteria alter their functional properties? For a better understanding of the early stages of cystic fibrosis, it is of major interest to study respiratory epithelial cells obtained as early as possible. Although bronchoalveolar lavage has been proposed for this purpose, nasal brushing, which is a much less invasive technique, has seldom been used in CF infants. the investigators have shown that, by means of a simple nasal brushing technique easily performed and well tolerated, it is feasible, in infants, to harvest native respiratory cell sheets in order to analyse the airway epithelium functionality. In 15 CF infants and 15 control infants, a nasal brushing will be performed by means of a soft sterile cytology brush. Samples will be used for cytological and functional studies: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities. These studies will be done in basal conditions and will be repeated after activation of the nasal epithelial cells by the bacteria, such as Staphylococcus aureus, which can be found very early in the course of CF disease.

the investigators believe that the present study could help to understand the pathophysiology on the very early stages of CF disease.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Reims, France, 51092
    • CHU Reims

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 6 months (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Cystic fibrosis

Exclusion Criteria:

• > 6 months old
• Other respiratory disease
• Other allergic disease
• Other infectious disease: fever (> 38° C), respiratory distress
• Altered general health state, rash,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main objective is to analyze the functionality of the respiratory epithelium in CF infant using a nasal brushing technique: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities.	In 15 CF infants and 15 control infants, a nasal brushing will be performed by means of a soft sterile cytology brush. Samples will be used for cytological and functional studies: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities.	no time frame

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Michel ABELY, Professor, CHU Reims

Publications and helpful links

General Publications

• Mosler K, Coraux C, Fragaki K, Zahm JM, Bajolet O, Bessaci-Kabouya K, Puchelle E, Abely M, Mauran P. Feasibility of nasal epithelial brushing for the study of airway epithelial functions in CF infants. J Cyst Fibros. 2008 Jan;7(1):44-53. doi: 10.1016/j.jcf.2007.04.005. Epub 2007 Jun 5.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): September 18, 2013
• Study Completion (Actual): September 18, 2013

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimated): May 25, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: C11-01; 2011-A00384-37 (Registry Identifier: IDRCB)