European guideline on indications, performance and clinical impact of 13 C-breath tests in adult and pediatric patients: An EAGEN, ESNM, and ESPGHAN consensus, supported by EPC

Abstract

Introduction: ¹³ C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers.

Methods: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of ¹³ C-breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and <10% disagreed.

Results: The guideline gives an overview over general methodology of ¹³ C-breath testing and provides recommendations for the use of ¹³ C-breath tests to diagnose Helicobacter pylori infection, measure gastric emptying time, and monitor pancreatic exocrine and liver function in adult and pediatric patients. Other potential applications of ¹³ C-breath testing are summarized briefly. The recommendations specifically detail when and how individual ¹³ C-breath tests should be performed including examples for well-established test protocols, patient preparation, and reporting of test results.

Conclusion: This clinical practice guideline should improve pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, this guideline identifies areas of future clinical research involving the use of ¹³ C-breath tests.

Keywords: breathtest; diagnosis; gastroenterology; gastroparesis; helicobacter pylori; liver cirrhosis; motility; pancreatic exocrine insufficiency; pancreatitis.

FIGURE 1

General principle of ¹³C‐breath testing. The ¹³C‐marked substrate is ingested, frequently with a specific test meal or test solution. Hepatic or bacterial enzymes release ¹³CO₂, this requires prior intraluminal metabolization and/or intestinal absorption for most tests. ¹³CO₂ is absorbed into the blood stream, transported to the lung, and exhaled. Breath samples are collected in glass tubes (mass spectroscopy) or aluminum bags (infrared spectroscopy) for measurement of ¹³C/¹²C‐ratio. Delta over basal values are used for calculation of ¹³C‐excretion. * for specific liver function tests the ¹³C‐marked substrate is applied intravenously

FIGURE 2

General principle, performance and clinical role of ¹³C‐breath tests used in gastroenterology. ¹³C‐urea used for detection of H. pylori (¹³C‐UBT, marked in green) is metabolized by bacterial urease to produce ¹³CO_2, which is absorbed, transported to the lung (broken green arrow) and exhaled. For ¹³C‐gastric emptying breath tests (¹³C‐GEBT, marked in red), ¹³C‐pancreatic function breath test (¹³C‐PFBT, marked in brown), and ¹³C‐liver function breath tests (¹³C‐LFBT, marked in blue), orally applied substrates or their metabolites are absorbed in the small intestine. Subsequently, they are transported to the liver where they undergo further metabolization with production of ¹³CO₂, which is transported to the lung and exhaled[Corrections added on June 28, 2021 after first online publication: Figure 3 (image and caption) has been revised.]