ORIGINAL ARTICLE Diagnosing lactase deficiency in three breaths M Oberacher 1 , D Pohl 2 , SR Vavricka 1 , M Fried 2 and R Tutuian 2,3 1 Department of Internal Medicine, Stadtspital Triemli, Zurich, Switzerland; 2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland and 3 University Clinics of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland Background: Lactose hydrogen breath tests (H 2 -BTs) are widely used to diagnose lactase deficiency, the most common cause of lactose intolerance. The main time-consuming part of the test relates to the sampling frequency and number of breath samples. Aim: Evaluate sensitivities and specificities of two- and three-sample breath tests compared with standard breath sampling every 15 min. Methods: Lactose H 2 -BT with probes samples every 15 min served as gold standard. Sensitivity, specificity, positive and negative predictive value of two-sample tests (0–60 min, 0–90 min or 0–120 min) and three-sample tests (0–60–90 min, 0–60–120 min or 0–90–120 min) were calculated. Results: Among 1049 lactose H 2 -BT performed between July 1999 and December 2005, 337 (32%) had a positive result. Two- sample tests had sensitivity and specificity of 52.5 and 100.0% (0–60 min), 81.9 and 99.7% (0–90 min), and 92.6 and 99.2% (0–120 min), respectively. Three-sample tests had sensitivity and specificity of 83.4 and 99.7% (0–60–90 min), 95.0 and 99.2% (0–60–120 min), and 95.0 and 98.9% (0–90–120 min), respectively. Conclusion: A three-sample breath test (baseline, 60/90 min and 120 min) has excellent sensitivity and specificity for lactase deficiency. Lactose H 2 -BT can be simplified but not shortened to o2 h. European Journal of Clinical Nutrition (2011) 65, 614–618; doi:10.1038/ejcn.2010.287; published online 19 January 2011 Keywords: lactose intolerance; lactose hydrogen breath test; lactase deficiency; hypolactasia Introduction Lactose intolerance is a common condition affecting a large proportion of the world’s population (Bayless et al., 1975). Lactose, a disaccharide, is a carbohydrate present only in mammalian milk accounting for around 7.2 g/l in human milk and 4.7 g/l in cow’s milk (Solomons, 2002). The prevalence of lactose intolerance differs in various parts of the world ranging from 3 to 8% in the Scandinavian and northwestern European population to 50–100% of the Asian population (Anh et al., 1977; Densupsoontorn et al., 2004; Farup et al., 2004). In Europe, the prevalence increases from north to south and west to east reaching a peak of 70% in southern Italy and Turkey (Gudmand-Hoyer, 1994). The most common cause of lactose intolerance is lactase deficiency, a condition of decreased production of lactase, the enzyme in the small intestinal villi responsible for splitting lactose into the absorbable monosaccharides glucose and galactose. In patients with lactose deficiency, the lactose reaches the large intestine where it is metabolized by the colonic flora. The high osmotic load caused by lactose in the small intestine and its bacterial metabolites produced mainly in the colon are considered to have an important role in the pathogenesis of classic symptoms of lactose intolerance such as diarrhea, bloating, nausea, borborygmi and abdominal pain. There are different methods in diagnosing lactase defi- ciency, including small bowel biopsy, measurement of the stool pH, oral administration of lactose followed by serial measurements of blood glucose, genetic analysis (Enattah et al., 2002; Pohl et al., 2010) or breath hydrogen concentra- tion. The lactose hydrogen breath test (H 2 -BT) has been used for more than 30 years, and is the preferred method to diagnose lactase deficiency in clinical practice (Newcomer et al., 1975). This test exploits the fact that, in contrast to human metabolism, the colonic flora metabolizes lactose into hydrogen (H 2 ), methane and short chain fatty acids. Hydrogen reaches the splanchnic venous circulation by diffusion through the intestinal wall, is transported from here through the portal system to the liver and the systemic circulation and is eventually exhaled through the lungs. Received 30 August 2010; revised 15 November 2010; accepted 30 November 2010; published online 19 January 2011 Correspondence: Dr R Tutuian, University Clinics of Visceral Surgery and Medicine, Inselspital Bern, Freiburgerstrasse, Bern CH-3010, Switzerland. E-mail: radu.tutuian@insel.ch European Journal of Clinical Nutrition (2011) 65, 614–618 & 2011 Macmillan Publishers Limited All rights reserved 0954-3007/11 www.nature.com/ejcn