Bronchial Trans-epithelial Transport in Patients With Idiopathic Multiple Dilations of the Bronchi

Study Overview
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Brief Summary
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The purpose of this study is to identify the abnormalities of bronchial trans-epithelial transport of chloride, sodium and bicarbonate in patients with idiopathic dilations of the bronchi.

Detailed Description
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Dilations of the bronchi happens for one child over 3000. The extended forms may progress to respiratory failure. More than one case over two remains of undetermined cause. If the prototype is the cystic fibrosis, other abnormalities of ionic transport may be the cause of a failure of mucociliary clearance and enhance the idiopathic dilations of the bronchi. The purpose of this study is to identify the abnormalities of bronchial trans-epithelial transport of chloride, sodium and bicarbonate in patients with idiopathic dilations of the bronchi, in comparison to two others groups of patients (without abnormality of ionic transport/with typical cystic fibrosis).

Official Title
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Study of the Bronchial Trans-epithelial Transport in Patients With Idiopathic Multiple Dilations of the Bronchi

Conditions
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Idiopathic Dilation of the Bronchi

Intervention / Treatment
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* Other: bronchial ddp test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Common criteria for all patients Age between 2 and 20 years. Patient weighing more than 12kg Patients with a scheduled bronchoscopy under clinical monitoring (assessment of bronchial involvement, local samples for bacteriological and histological examination) Signature of consent by the patient or by the / the holder (s) of parental authority and the investigator Patient affiliated to a social security scheme or entitled Patient with contraception (for woman of childbearing age) Specific criteria for idiopathic bronchiectasis patients Patient with idiopathic bronchiectasis in at least two lobes, diagnosis made after extensive screening of known acquired or congenital causes Specific criteria for control patients without abnormal ion transport Patient Not having bronchiectasis s or any supposed alteration in transepithelial ion transport Patients with fiberoptic bronchoscopy performed for one of the following indications: Pulmonary malformations Laryngeal, tracheal, bronchomalacia Airway compression Interstitial pathology Suspicion of foreign body Suspected tuberculosis Specific criteria for patients with a typical form of cystic f ibrosis (CF) Patient carrying 2 causing mutations in the CFTR gene (according to CFTR2 database; http://www.cftr2.org/mutations_history.php) and sweat test> 60 milliequivalent per liter (mEq/L). Exclusion Criteria: Common criteria for all patients Smoking passive or active Not essential bronchial endoscopy in the clinical follow Extension of bronchoscopy time attributed to the difference in potential bronchial incompatible with the patient's general status Patient pregnant or breast feeding Hypersensitivity or cons known contraindications to health products for measurement of DDP (isoproterenol, Amiloride, ATP) Specific criteria for idiopathic DDB patients Presence of other congenital or acquired etiologies of DDB: Typical or atypical cystic fibrosis, Immunodeficiency, Primary ciliary dyskinesia, Abnormal bronchial wall structure (Williams-Campbell syndrome, Mounier-Kuhn, Ehlers-Danlos syndrome, Marfan's disease) Infectious DDBs post Extrinsic or endobronchial obstruction (foreign body, malformation, middle lobe syndrome) Chronic inhalation (GERD, swallowing disorders, gastroesophageal tracheal fistula) Allergic bronchopulmonary aspergillosis, System disease.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with multiple bronchi dilations<br> | Other: bronchial ddp test<br>* bronchial ddp test during endoscopy, nasal smear, bronchial smear<br>|
| Active Comparator: Control patients without transport abnormality<br> | Other: bronchial ddp test<br>* bronchial ddp test during endoscopy, nasal smear, bronchial smear<br>|
| Active Comparator: Patients with typical cystic fibrosis<br> | Other: bronchial ddp test<br>* bronchial ddp test during endoscopy, nasal smear, bronchial smear<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to isoproterenol in solution without chloride ions during bronchial potential difference test (ΔIsoprotérénol / bronchial). | Difference between groups for Level of repolarisation | up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to amiloride during bronchial potential difference test | Trans-epithelial transport measured in vivo | up to 5 days | 
| trans-epithelial ionic transport in the nasal epithelium (nasal DDP) | Trans-epithelial transport measured in vivo | up to 5 days | 
| trans-epithelial ionic transport of sweat epithelium (sweat test) | Trans-epithelial transport measured in vivo | up to 5 days | 
| Basal current short circuit | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Response to Epithelial Sodium Channel (ENaC) inhibitors | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Activation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) (inh-172) | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Activation of Calcium (Ca)-dependent Chloride (Cl-) ion channels | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Inhibition of Solute Carrier family 26, member 9 (SLC26A9) | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Response to inhibitors of potassium (K+ ) secretion basolateral | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 
| Bicarbonate (HCO3- ) secretion in response to forskolin | Trans-bronchial epithelial ionic transport evaluated in vitro on bronchial primary cultures | up to 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dilation of the Bronchi, Bronchial potential difference, Dilation of the Bronchi (DDB)