Added Value of C Analysis in Breath Tests in H-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

INTRODUCTION

Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled CO after ingestion of C-lactose has been proposed to mitigate this problem.

OBJECTIVE

The aim of the study was to assess the performance of measuring methane and CO in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test.

METHODS

Individuals referred for lactose breath testing and healthy controls were included. Participants received C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and CO excretion was assessed.

RESULTS

151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20 ppm above baseline. In subjects with normal hydrogen excretion, cumulative C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10 ppm).

CONCLUSIONS

In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of C-lactose with measurement of CO excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.