Poor reproducibility of breath hydrogen testing: Implications for its application in functional bowel disorders

Abstract

Background: Limited data are available regarding the reproducibility of lactulose and fructose breath testing for clinical application in functional bowel disorders. Objectives: The purpose of this study was to investigate the reproducibility of lactulose and fructose breath hydrogen testing and assess symptom response to fructose testing. Methods: Results were analysed from 21 patients with functional bowel disorder with lactulose breath tests and 30 with fructose breath tests who completed another test >2 weeks later. Oro-caecal transit time, hydrogen responses, both qualitatively (positive/negative) and quantitatively (area under the curve (AUC) for hydrogen), were compared between tests. In another 36 patients, data scores for overall abdominal symptoms, abdominal pain, bloating, wind, nausea and fatigue were collected during the fructose test and compared to hydrogen responses. Results: No correlations were found for lactulose AUC (linear regression, p ¼ 0.58) or transit time (Spearman's p ¼ 0.54) between tests. A significant proportion (30%) lost the presence of fructose malabsorption (p < 0.01). Hydrogen AUC for fructose did not correlate between tests, (r ¼ 0.28, p ¼ 0.17) independent of time between testing (p ¼ 0.82). Whilst patients with fructose malabsorption were more likely to report symptoms than those without (56% vs 17%; p ¼ 0.04), changes in symptom severity were not different (p > 0.05). Conclusions: Routine use of lactulose and fructose breath tests in functional bowel disorder patients is not supported due to its poor reproducibility and low predictive value for symptom responses.

Editorial: rethinking predictors of response to the low FODMAP diet – should we retire fructose and lactose breath‐hydrogen testing and concentrate on visceral hypersensitivity?

“…The authors have previously reported that response to the diet does not correlate with the presence of malabsorption itself, but rather is associated with the induction of symptoms in those with malabsorption . This is in line with our reported lack of association of the induction of symptoms with the presence of malabsorption of fructose, sorbitol or mannitol . What is missing is specific study of the dietary response of patients without malabsorption, with or without symptom induction.…”

Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions

“…However, significant limitations exists due to poor reproducibility to both lactulose and fructose, and poor correlation with symptom induction to fructose challenge, poor applicability of test doses to real‐life consumption in the diet, and the risk of negative breath test results inappropriately steering patients away from dietary therapy …”

“…Scintigraphy suggests measuring an early‐rise in breath hydrogen following lactulose indicates oro‐cecal transit as opposed to SIBO . Additionally, variations within individuals following lactulose occur over time when using the early‐rise in breath hydrogen criteria for SIBO . The alternative of using glucose breath testing is also problematic as glucose is rapidly absorbed proximally in the small intestine.…”

Repeatability and effect of blinding of fructose breath tests in patients with functional gastrointestinal disorders

“…The sole published study addressing a related issue we have discovered is a post hoc study of the reproducibility of hydrogen production during fructose breath across varying study protocols and settings, in patients preselected for their breath test responses. A poor reproducibility of malabsorption testing using hydrogen concentrations was reported, albeit applying statistical methodology (correlation tests) not suitable for assessment of repeatability . The definitions of repeatability and reproducibility differ as follows: Repeatability of measurements refers to the variation in repeat measurements made on the same subject under identical conditions, by the same instrument or method, the same observer and that the measurements are made over a short period of time, over which the underlying value can be considered to be constant.…”

“…The dose and formulation of fructose used in breath tests is the topic of ongoing discussions and the cut‐off thresholds for definition of intolerance and malabsorption remain arbitrary. The doses and thresholds used in the current studies corresponded to those used in previous publications for comparative reasons . As it is not known whether the repeatability or expectation effects of fructose breath testing differ with varying fructose doses, this should be further examined.…”