Development of an interval sampling hydrogen (H2) breath test for carbohydrate malabsorption in children: evidence for a circadian pattern of breath H2 concentration.

Abstract

Summary: We have applied the gas chromatographic analysis of hydrogen (H2) in expired air to the determination of carbohydrate malabsorption in children. A compact, inexpensive, and simple gas chromatograph was specifically adapted to the measurement of low concentration of H2. A collection procedure using the sampling of expired air at evenly spaced intervals with a low resistance facemask was used to obviate the need for closed, continuous rebreathing systems of breath collection. Under different experimental conditions, H2 concentrations ranged from 11–166 ppm. During fasting, however, H2 concentrations in preschool children were extraordinarily stable and uniform. The velocity of H2 excretion from graded doses of 1.5, 3, and 6 g of the nonabsorbable disaccharide, lactulose, was linear with a response of 1.2 cc H2/2 hr/g nonabsorbed carbohydrate. Formal clinical lactose tolerance tests were devised using the oral administration of 1.75 g lactose/kg body weight. The increase in II2 concentration was compared with the rise in plasma glucose. Maximum increases in H2 concentration of less than 15 ppm corresponded to a rise in plasma glucose greater than 20 mg/dl; increases in H2 of more than 20 ppm were uniformly accompanied by flat glucose curves. Increases in H2 concentration between 15 and 20 ppm comprised a borderline zone in which both flat and normal glucose curves were seen. The normal absorption of the monosaccharide constituents of lactose, glucose, and galactose, as demonstrated by increments of less than 15 ppm in H2, indicates that the lactose intolerance was due to failure of digestion of the disaccharide rather than to decreased mucosal absorption of the monosaccharide products. When H2 concentration was measured at 120-min intervals over periods of 24 hr in children on a normal diet, a 2.5-fold or greater increment in breath H2 concentration was observed at some time during nocturnal sleep. Moreover, the increase in H2 concentration to a standard dose of 6 g lactulose was greater during induced sleep than in the awake subject. Various pitfalls to the interpretation of clinical carbohydrate absorption tests using breath H2 were identified. These included an occasionally elevated baseline concentration of H2, delayed gastric emptying, and previous administration of broad spectrum oral antibiotics. The test is noninvasive, well tolerated, semiquantitative, and ideally suited for use in children. Speculation: The noninvasive, interval sampling of H2 breath test will provide a more versatile, widely applicable, and better tolerated index of carbohydrate malabsorption in the pediatric population than conventional methods using blood glucose determinations, and will prove to be the preferred method for testing carbohydrate tolerance in children.