Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia

Examination of the Cardiorespiratory Performance Capacity and Pulmonary Microbiome in Patients Following Surgical Repair of Esophageal Atresia

The majority of the clinical research on esophageal atresia focuses on the upper gastrointestinal tract. However, the trachea and the lung are also affected in many of these children, so that a lifelong pulmonary impairment may result. The importance of respiratory function in the context of follow-up of these patients has therefore been increasingly recognized in recent years. Scientific work has shown significantly, that patients following esophageal atresia repair develop respiratory symptoms more frequently than the normal population. Mild impairment of the pulmonary function in adolescence and adulthood was demonstrated in some studies, but to date, there is no exact idea about the relationship between early childhood disease progression and later pulmonary impairment. Only a few scientific papers have dealt with the effect of impaired pulmonary function on the physical capacity of these adolescents and adults. Most of these studies show small case numbers, inconclusive stress tests, and divergent results.

The aim of this prospective study is to investigate the cardiopulmonary performance capacity and the pulmonary microbiome of adolescent and adult patients with corrected esophageal atresia and to compare the results with a control group. Another focus of the investigators is on the composition of the pulmonary microbiome of the participants. Changes of the pulmonary microbiome and the influence on the cardio-pulmonary performance capacity have not yet been investigated. Furthermore, it should be investigated whether the treatment measures and a complicated disease course in the neonatal period have long-term effects on lung function, exercise capacity and composition of the microbiome in the lungs.

Study Overview

• Status: Unknown
• Conditions: Esophageal Atresia
• Intervention / Treatment: Diagnostic test: Initial Spirometry; Diagnostic test: Final Spirometry; Diagnostic test: Pulmonary microbiome (16S rDNA profiling); Diagnostic test: Maximum oxygen uptake; Diagnostic test: Maximum performance; Diagnostic test: weight; Other: age

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Recruiting
    • Medical University of Graz
    • Contact: Jana Windhaber, MD; Phone Number: 83770 01143316385; Email: jana.windhaber@medunigraz.at
    • Contact: Christoph Arneitz, MD; Phone Number: 80358 01143316385; Email: christoph.arneitz@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age from 12 years
• Status post surgical correction of esophageal atresia with and without fistula
• Granted consent

Exclusion Criteria:

• Acute infections within the last 14 days
• Other associated serious malformations
• Acute, temporary respiratory complaints (cough, allergies etc.)
• Physical and mental illnesses or disabilities that do not allow the examination to be carried out
• non-granted consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Patients after esophageal atresia; Patients older than 12 years following surgical repair of congenital esophageal atresia will be included after written informed consent. Patients will be subjected to spirometry to determine their age, weight (determined by Kilogram (kg) on a medical weight scale) and Vital Capacity before (initial Spirometry) and after (final Spirometry) exercise performance testing. Bicycle ergospirometer will be applied to determine the Maximum Oxygen Uptake and the Maximum Performance. Thereafter deep induced sputum will be harvested for measurements of the pulmonary microbiome (Pulmonary Microbiome 16S rDNA profiling).	Diagnostic test: Initial Spirometry; Determination of Vital Capacity by spirometry before (within 30 minutes) spiroergometry. Measurements will be performed in both groups.; Diagnostic test: Final Spirometry; Determination of Vital Capacity by spirometry after (within 30 minutes) spiroergometry. Measurements will be performed in both groups.; Diagnostic test: Pulmonary microbiome (16S rDNA profiling); Harvesting of deep induced sputum and determination of the airway microbiome by 16S ribosomal RNA (rRNA) pyrosequencing. Evaluation of alpha and beta diversity and relative bacterial abundance at the genus level. Measurements will be performed in both groups (samples will be harvested within 30 minutes after spiroergometry).; Diagnostic test: Maximum oxygen uptake; Determination of the maximum oxygen uptake (ml/kg/min) corrected for gender, age and body weight by bicycle spiroergometry. Measurements will be performed in both groups.; Diagnostic test: Maximum performance; Determination of the maximum performance (W/kg) corrected for body weight by bicycle spiroergometry. Measurements will be performed in both groups.; Diagnostic test: weight; Determined by Kilogram on a medical weight scale; Other: age; Determination of age by patient's Report and past medical history
ACTIVE_COMPARATOR: Control group; Age and sex matched adolescents will be recruited as control group and will be included after written informed consent. Adolescents will be subjected to spirometry to determine their age, weight (determined by Kilogram on a medical weight scale) and Vital Capacity before (initial Spirometry) and after (final Spirometry) exercise performance testing. Bicycle ergospirometer will be applied to determine the Maximum Oxygen Uptake and the Maximum Performance. Thereafter deep induced sputum will be harvested for measurements of the pulmonary microbiome (Pulmonary Microbiome 16S rDNA profiling).	Diagnostic test: Initial Spirometry; Determination of Vital Capacity by spirometry before (within 30 minutes) spiroergometry. Measurements will be performed in both groups.; Diagnostic test: Final Spirometry; Determination of Vital Capacity by spirometry after (within 30 minutes) spiroergometry. Measurements will be performed in both groups.; Diagnostic test: Pulmonary microbiome (16S rDNA profiling); Harvesting of deep induced sputum and determination of the airway microbiome by 16S ribosomal RNA (rRNA) pyrosequencing. Evaluation of alpha and beta diversity and relative bacterial abundance at the genus level. Measurements will be performed in both groups (samples will be harvested within 30 minutes after spiroergometry).; Diagnostic test: Maximum oxygen uptake; Determination of the maximum oxygen uptake (ml/kg/min) corrected for gender, age and body weight by bicycle spiroergometry. Measurements will be performed in both groups.; Diagnostic test: Maximum performance; Determination of the maximum performance (W/kg) corrected for body weight by bicycle spiroergometry. Measurements will be performed in both groups.; Diagnostic test: weight; Determined by Kilogram on a medical weight scale; Other: age; Determination of age by patient's Report and past medical history

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary microbiome (16S rDNA profiling) - Alpha diversity	Determination of alpha diversity (Chao1 Test) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of Alpha diversity (Chao1 Analysis) between patients after repair of esophageal atresia and age and sex matched healthy controls.	1 year
Pulmonary microbiome (16S rDNA profiling) - Beta diversity	Determination of beta diversity (unweighted UniFrac test) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of beta-diversity (Unweighted UniFrac Analysis) between patients after repair of esophageal atresia and age and sex matched healthy controls.	1 year
Pulmonary microbiome (16S rDNA profiling) - relative bacterial abundance	Determination of relative bacterial abundance (in per Cent) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of relative bacterial abundance (Mann-Whitney-U-Test) between patients after repair of esophageal atresia and age and sex matched healthy controls.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum oxygen uptake (ergospirometer)	Maximum oxygen uptake (corrected for age, gender and body weight ) as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.	1 year
Maximum Performance (ergospirometer)	Maximum performance as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.	1 year
Vital capacity (spirometry)	Vital capacity as determined by spirometry. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.	1 year

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Study Director: Jana Windhaber, MD, Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria; Study Chair: Holger Till, MD, Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria; Principal Investigator: Christoph Arneitz, MD, Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 10, 2017
• Primary Completion (ANTICIPATED): April 6, 2019
• Study Completion (ANTICIPATED): September 2, 2019

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (ACTUAL): December 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 6, 2018
• Last Update Submitted That Met QC Criteria: December 5, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Gastrointestinal Diseases; Esophageal Diseases; Digestive System Abnormalities; Esophageal Atresia
• Other Study ID Numbers: 1.1

Drug and device information, study documents

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