Reversibility of Bronchial Obstruction in Children Born Preterm

Bronchodilator Response To Inhaled Beta-2 Agonist and Anticholinergic Drugs in Children Born Preterm

This observational study aims to compare responses to different, commonly used inhaled bronchodilators in children born preterm with bronchial obstruction at spirometry. All children were diagnosed with Chronic Lung Disease of Immaturity (CLDI).

The main questions are:

• Is any inhaled bronchodilator or their combination generally superior in children with CLDI when assessing the reversibility of bronchial obstruction?
• Is there an individual difference in the effect of betamimetic, anticholinergic or their combination between children with CLDI?

Participants will:

• Come to our clinic in a stable state without acute infection and they will be randomly assigned to the first inhaled bronchodilator.
• They will then perform a spirometry test before and after the inhalation of the drug.
• This visit will repeat 3 times, each with a different bronchodilator (beta2agonist, anticholinergic and their combination).

Study Overview

• Status: Recruiting
• Conditions: Bronchopulmonary Dysplasia; Chronic Lung Disease of Prematurity; Bronchial Hyperreactivity; Preterm Birth Complication; Chronic Lung Disease of Newborn; Bronchial Obstruction; Reversible Dilatation

Detailed Description

1. Outpatient follow-up - Parents are asked to sign the study consent form if the child meets the indication criteria. If the trial subject is not taking inhaled therapy, he/she may immediately continue to Check-up A. If the subject is taking short- or long-acting bronchodilators, these medications must be discontinued before each check-up and at the following intervals:

   • Short-acting β2 agonists (SABA) - 12 hours before the examination
   • Short-acting inhaled cholinergic antagonists (e.g. ipratropium bromide) - 12 hours before the examination
   • Long-acting inhaled betamimetics (long-acting β2 agonists, LABAs) - 48 hours before the examination
   • Long-acting muscarinic antagonists (LAMA) - one week before the examination

2. Check-up A - Baseline pre-interventional spirometry may be performed if the subject has no evidence of acute respiratory infection or has not had an acute respiratory infection two weeks previously. Otherwise, the examination should be rescheduled. Before baseline spirometry, the child is randomized to a dilatation test with inhaled salbutamol, ipratropium, or a combination of fenoterol/ipratropium. After a defined time interval (15 - 30 minutes), post-interventional spirometry follows.

   The subject is invited to attend Check-up B (which preferably follows 1 to 30 days after Check-up A, but no later than 3 months).

3. Check-up B - Baseline pre-interventional spirometry may be performed if the subject has no evidence of acute respiratory infection or has not had an acute respiratory infection two weeks previously. Otherwise, Check-up B should be rescheduled. Before baseline spirometry, another inhaled bronchodilator according to the preceding randomisation is applied. After a defined time interval (15 - 30 minutes), post-interventional spirometry follows. Resting spirometry with a dilatation test with another drug, the choice of which is guided by randomization, is performed.
4. Check-up C - Baseline pre-interventional spirometry may be performed if the subject has no evidence of acute respiratory infection or has not had an acute respiratory infection two weeks previously. Otherwise, Check-up C should be rescheduled. Baseline spirometry with the last bronchodilator not yet used is performed.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Jana Tukova, MD, PhD; Phone Number: +420608116653; Email: tukovajana@seznam.cz
• Study Contact Backup: Name: Yotam Ophir, MD; Phone Number: +420608199927; Email: yotkeofire@gmail.com

Study Locations

• Czechia
  • Prague, Czechia, 128 00
    • Recruiting
    • First faculty of Medicine, Charles university.
    • Contact: Ilona Trtikova, Mgr., PhD; Phone Number: +420224965613; Email: ilona.trtikova@lf1.cuni.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

children born preterm before 35+0 of gestational age (35+0) with chronic lung disease of prematurity with bronchial obstruction, confirmed by spirometry.

Description

Inclusion Criteria:

• children born preterm /before the 35th week of gestational age (35+0)/
• all subjects must have chronic lung disease of prematurity with bronchial obstruction, confirmed by spirometry
• subjects must be able to cooperate well in spirometry

Exclusion Criteria:

• The presence of another chronic respiratory disease (e.g., cystic fibrosis, primary ciliary dyskinesia, etc.). Asthma bronchiale is not an exclusion criterion, but subjects with CLDI combined with asthma bronchiale represent a specific subgroup of subjects and we perform a standardized therapeutic test with inhaled corticosteroids (ICS) administered for at least 12 weeks via a pressurized aerosol dispenser (pMDI) via an inhaler attachment before enrollement.
• Insufficient cooperation during spirometry.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of spirometric parameters of bronchial obstruction in children born preterm to inhaled salbutamol, ipratropium bromide and combination of fenoterol with ipratropium bromide	Spirometric parameters of bronchial obstruction before and after inhaled application of bronchodilator during check-up. Three types of bronchodilators (salbutamol, ipratropium bromide and combined inhaler of fenoterol with ipratropium bromide) at three different check-ups will be tested with the order selected by randomisation. Z-score of baseline (pre-interventional) spirometric expiratory flow parameters (MMEF (l/s), MEF75 (l/s), MEF50 (l/s), MEF25 (l/s) retrieved from flow-volume curve compared to post-interventional z- scores of MMEF (l/s), MEF75 (l/s), MEF50 (l/s), MEF25 (l/s) values measured after a predefined time interval specific to bronchodilator (15-30 minutes). Four standardised doses of bronchodilators will be administered with metered-dose inhaler by spacer without a mask.	baseline and post-interventional spirometry after 15-30 minutes (interval specific to bronchodilator) during three check-ups with min. time interval between check-ups 24 hours and max. 30 days
Change of spirometric parameters of lung volume in children born preterm to inhaled salbutamol, ipratropium bromide and combination of fenoterol with ipratropium bromide	Spirometric parameters of lung volume before and after inhaled application of bronchodilator during check-up. Three types of bronchodilators (salbutamol, ipratropium bromide and combined inhaler of fenoterol with ipratropium bromide) at three different check-ups will be tested with the order selected by randomisation. Z-score of baseline (pre-interventional) spirometric volume parameters FEV 0.5 (ml), FVC (ml) retrieved from flow-volume curve compared to post-interventional z- scores of FEV 0.5 (l), FVC (l) values measured after a predefined time interval specific to bronchodilator (15-30 minutes). Four standardised doses of bronchodilators will be administered with metered-dose inhaler by spacer without a mask.	baseline and post-interventional spirometry after 15-30 minutes (interval specific to bronchodilator) during three check-ups with min. time interval between check-ups 24 hours and max. 30 days
Change of area under the flow-volume spirometric curve in children born preterm to inhaled salbutamol, ipratropium bromide and combination of fenoterol with ipratropium bromide	Complex spirometric parameter of area under the curve before and after inhaled application of bronchodilator during check-up. Three types of bronchodilators (salbutamol, ipratropium bromide and combined inhaler of fenoterol with ipratropium bromide) at three different check-ups will be tested with the order selected by randomisation. Z-score of baseline (pre-interventional) Aex (l*l/s) retrieved from flow-volume curve compared to post-interventional z- scores of Aex (l*l/s) values measured after a predefined time interval specific to bronchodilator (15-30 minutes). Four standardised doses of bronchodilators will be administered with metered-dose inhaler by spacer without a mask.	baseline and post-interventional spirometry after 15-30 minutes (interval specific to bronchodilator) during three check-ups with min. time interval between check-ups 24 hours and max. 30 days

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Investigators: Principal Investigator: Jana Tukova, MD,PhD, Charles University, Czech Republic First Faculty of Medicine, Prague

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: October 29, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Bronchial Diseases; Lung Injury; Ventilator-Induced Lung Injury; Premature Birth; Lung Diseases; Bronchopulmonary Dysplasia; Bronchial Hyperreactivity
• Other Study ID Numbers: CZ-VFN-PEDMET-BPD-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No