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

Not Applicable

• Conditions: Esophageal Atresia
• Interventions: 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

• Registration Number: NCT03767673
• Lead Sponsor: Medical University of Graz

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-10
• Study First Submitted: 2018-07-19
• Status Verified: 2018-12
• Study First Submitted QC: 2018-12-05
• Last Update Submitted: 2018-12-05
• Study First Posted: 2018-12-06
• Last Update Posted: 2018-12-06
• Primary Completion: 2019-04-06
• Study Completion: 2019-09-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients after esophageal atresia	Initial Spirometry	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).
Patients after esophageal atresia	age	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).
Control group	Initial Spirometry	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).
Patients after esophageal atresia	Final Spirometry	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).
Patients after esophageal atresia	Maximum performance	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).
Patients after esophageal atresia	weight	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).
Control group	Maximum performance	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).
Patients after esophageal atresia	Maximum oxygen uptake	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).
Patients after esophageal atresia	Pulmonary microbiome (16S rDNA profiling)	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).
Control group	Pulmonary microbiome (16S rDNA profiling)	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).
Control group	weight	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).
Control group	Final Spirometry	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).
Control group	Maximum oxygen uptake	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).
Control group	age	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).

Primary Outcome Measures

Name	Time	Method
Pulmonary microbiome (16S rDNA profiling) - Alpha diversity	1 year	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.
Pulmonary microbiome (16S rDNA profiling) - Beta diversity	1 year	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.
Pulmonary microbiome (16S rDNA profiling) - relative bacterial abundance	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Maximum oxygen uptake (ergospirometer)	1 year	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.
Maximum Performance (ergospirometer)	1 year	Maximum performance as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.
Vital capacity (spirometry)	1 year	Vital capacity as determined by spirometry. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.

Trial Locations

Locations (1)

Medical University of Graz; 🇦🇹 Graz, Austria