Effects of Prenatal Tobacco Smoke Exposure on Lung Function and Respiratory Epithelium Functionality in Newborns

Effets du Tabagisme in Utero Sur la fonctionnalité de l'épithelium Respiratoire et Sur la Fonction Ventilatoire du Nouveau-né.

Despite public campaigns to prevent cigarette smoking, it's about 20% of women who keep on smoking during pregnancy, exposing their fetus to prenatal tobacco adverse effects. Although environnemental tobacco smoke exposure effects are well known, consequences of prenatal tobacco smoke exposure (PTSE) need better caracterization. Previous animal study from our group have shown, in prenatal nicotine exposed mouse pups, alterations in tracheal epithelial structure similar to those observed in KO α7-nAChR mouse pups. These findings support the hypothesis that α7-nAChR are involved in the process of deleterious effects of tobacco smoking on respiratory epithelium development. The purpose of the present clinical study is to compare PTSE neonates with controls according to lung function and respiratory epithelial functionality. At the age of 3 days, small respiratory epithelium fragments will be obtained from gentle nasal brushing performed under antalgic premedication according to the method we previously published. Epithelium samples will be used for in vitro studies of α7-nAChR and CFTR functionality. Between the ages of 2 and 6 weeks, lung function testing will be performed, by means of baby-body plethysmography.

Study Overview

• Status: Completed
• Conditions: Tobacco Smoking; Pregnancy Related; Newborn; Lung Smokers
• Intervention / Treatment: Diagnostic test: lung function tests; Diagnostic test: Nasal brushing

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75000
    • Inserm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 6 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• inborn full-term neonate
• social security affiliation
• informed consent form signed by parents

Exclusion Criteria:

• prematurity < 35GW
• gemellary pregnancy
• Birth weight < 2200 g
• neonatal respiratory distress syndrome (nasal oxygenotherapy > 24 hours, invasive or noninvasive ventilation)
• neonatal malformation with conséquences on lung function
• neonatal liver or renal failure
• high risk of heritable lung disease
• contra-indication to saccharose or paracetamol antalgic use
• language barrier,
• mother refusal to declare or precise her tobacco consumption
• no social security cover
• informed consent form not signed

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PTSE; Prenatal tobacco smoke exposed newborns. Lung function test Nasal brushing	Diagnostic test: lung function tests; baby-body plethysmography; Diagnostic test: Nasal brushing; Epithelial sample collecting for in vitro study
Experimental: control; Prenatal tobacco smoke non exposed newborns Lung function test Nasal brushing	Diagnostic test: lung function tests; baby-body plethysmography; Diagnostic test: Nasal brushing; Epithelial sample collecting for in vitro study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
α7-nAChR functionnality	calcium influx mesurements on epithelial fragments by monitoring changes in Fluo-4 fluorescence intensity. Fluo-4 is a fluorescent dye which fluorescence is modified by its linkage to Calcium. Its fluorescence changes measurements shows calcium cellular flows.	day 3
CFTR functionality	chlorid influx study on epithelial fragmentsby monitoring changes in spq fluorescence intensity. sqp is a fluorescent dye which fluorescence is modified by its linkage to Chlore. Its fluorescence changes measurements shows chlore cellular flows.	day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung function test	baby-body plethysmography that study ventilation in asleep infants (measurement of tidal volumes, respiratory frequency, airway resistances, respiratory system compliance, maximal expiratory flows)	between ages 2 and 6 week
ciliary frequency mesurement	On epithelial fragments. By using vidéo microscopy and select several delimited zone where ciliary frequency is measured. Then a mean freqeuncy is calculated	day 3

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Study Director: Pierre MAURAN, MD PHD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2017
• Primary Completion (Actual): February 9, 2018
• Study Completion (Actual): February 9, 2019

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: February 6, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: C15-60

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No