Abstract
The aim of this study was to analyze the exhaled volatile organic compounds (VOCs) profile, airway microbiome, lung function and exercise performance in congenital diaphragmatic hernia (CDH) patients compared to healthy age and sex-matched controls. A total of nine patients (median age 9 years, range 6–13 years) treated for CDH were included. Exhaled VOCs were measured by GC–MS. Airway microbiome was determined from deep induced sputum by 16S rRNA gene sequencing. Patients underwent conventional spirometry and exhausting bicycle spiroergometry. The exhaled VOC profile showed significantly higher levels of cyclohexane and significantly lower levels of acetone and 2-methylbutane in CDH patients. Microbiome analysis revealed no significant differences for alpha-diversity, beta-diversity and LefSe analysis. CDH patients had significantly lower relative abundances of Pasteurellales and Pasteurellaceae. CDH patients exhibited a significantly reduced Tiffeneau Index. Spiroergometry showed no significant differences. This is the first study to report the VOCs profile and airway microbiome in patients with CDH. Elevations of cyclohexane observed in the CDH group have also been reported in cases of lung cancer and pneumonia. CDH patients had no signs of impaired physical performance capacity, fueling controversial reports in the literature.
Highlights
Nine patients following surgical repair of a congenital diaphragmatic hernia (CDH) were recruited for long-term followup examinations consisting of assessment of the exhaled volatile organic compounds (VOCs) profile, airway microbiome, lung function and exercise performance
Box plots were drawn with Prism 8.3.0® (GraphPad, San Diego, CA, USA) and heatmaps with R Studio 1.2.1335® (RStudio Inc., Boston, MA, USA) using the heatmap.2 library. This is the first study to report on the airway microbiome and VOC
The alterations of the microbiome were minor and the clinical consequence of reduced Pasteurellaceae remains unclear at present
Summary
Congenital diaphragmatic hernia (CDH) is a rare disease occurring with an incidence of 1:2000–1:5000 live births [1]. CDH is caused by disturbances in the formation of the diaphragm in the eighth week of gestation, leaving a defect with persistent communication between the abdominal and thoracic cavity [2]. This defect is located in the dorsal aspect of the diaphragm (Bochdalek hernia, 95% of cases, mostly located on the left side). Ventral hernias (Morgagni hernia) are rarer and typically located on the right side [3]
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