Lactulose Breath Testing Does Not Discriminate Patients With Irritable Bowel Syndrome From Healthy Controls

Jason R. Bratten, B.S.; Jennifer Spanier, D.O.; Michael P. Jones, M.D.

Disclosures

Am J Gastroenterol. 2008;103(4):958-963. 

In This Article

Methods

Consecutive patients referred for LBT for clinical indications, and meeting Rome II criteria for IBS as well, were prospectively studied. Patients were interviewed by the investigators at the time of enrollment, and endorsed at least two of three cardinal Rome II criteria (abdominal pain relieved with defecation, onset associated with a change in frequency of stool, and/or onset associated with a change in form/appearance of stool). Additionally, they were asked to identify a dominant bowel pattern (constipation, diarrhea, or mixed), and asked if bloating was a troublesome symptom for them. Healthy controls were recruited by advertisements placed in various locations on the Northwestern University graduate and undergraduate campuses, as well as in Northwestern Memorial Hospital. Patients and controls were interviewed personally by the investigators to exclude any active digestive disorder (other than IBS for patients) or history of a digestive or systemic condition that might alter intestinal motility. Patients and controls were also excluded if there was a history of abdominal surgery, other than appendectomy or hysterectomy, use of motility-modifying medications (such as prokinetics, narcotics, calcium channel blockers, or anticholinergics), or use of antibiotics within the past month. Controls received a $20 study payment for participation at the completion of the study. Patients with IBS undergoing clinical testing were not compensated. The study was approved by the institutional review board at Northwestern University. All patients and controls gave informed consent immediately prior to undergoing breath testing.

LBT were performed in the gastroenterology physiology laboratory of Northwestern Memorial Hospital at 0800 h following an overnight fast of at least 12 h. Prior to testing, patients were instructed to avoid slow-digesting foods (beans, bran, or high-fiber foods) or a heavy meal for dinner the night before evaluation. Good oral hygiene was recommended. Smoking and exercise were not permitted on the day of testing.

Patients ingested 10 g of lactulose (Kristalose™, Inalco Spa, Milano, Italy; distributed by Bertek Pharmaceuticals, Inc., Sugarland, TX) dissolved in 240 mL of water.[21] End-alveolar breath samples were then collected using the Alveosampler™ (QuinTron Instrument Company, Milwaukee, WI). Breath samples were obtained at baseline and at 20, 40, 60, 80, 100, 120, 150, and 180 min after lactulose ingestion. Breath H2 and methane (CH4) concentrations were measured immediately after collections using a MicroLyzer Model DP Plus (QuinTron Instrument Company), and plotted graphically by a trained technician. The MicroLyzer was calibrated daily and during every 30 min of operation using reference gas mixtures provided by the manufacturer. Desiccants in the drying tubes are changed weekly, or sooner if there is a change in desiccant color. All studies were performed by the same trained technician (JRB), who has over 3 yr of experience in breath testing.

LBT were interpreted by an experienced clinician (MPJ), who was blinded to subject condition and symptoms. Criteria for a normal test were those previously published by Pimentel et al., and included no rise in breath H2 within 90 min after lactulose administration, with a definitive rise in breath H2 that never exceeded 20 ppm during the 180-min measurement period.[10,11] LBT was considered abnormal if there were dual breath H2 peaks defined as a 12-ppm increase in breath H2 over baseline with a decrease of ≥5 ppm before the second peak.[10] The orocecal transit time was calculated as the earliest time at which a sustained increase in breath H2 of >5 ppm over baseline value was seen.[22,23]

Subjects were defined as CH4 producers if breath CH4 concentrations at baseline were ≥1 ppm or breath CH4 at any concentration was detected during the test.[24] Because of the confounding effects of methanogenic flora on breath H2 levels, breath H2 profiles of CH4-producing subjects were excluded from analysis.[25]

The primary aim of the study is to test the null hypothesis that the proportion of positive LBT is identical between controls and patients with IBS. The criterion for significance (alpha) was set at 0.050, and is 2-tailed. A sample size of at least 42 patients for each of the two groups provides 80% power to yield a statistically significant result, assuming that the difference in proportions between groups is 0.30 (specifically, 0.70 vs 0.40). This effect was selected based on the existent literature, and as the smallest effect that would be important to detect clinically. The second goal of the study is to estimate the difference between the two populations. Based on these same parameters and assumptions, the study will enable us to report the difference in proportions with a precision (95% confidence interval [CI]) of approximately ±20%.

Data are expressed as mean ± standard deviation (SD). Normality of all data sets was determined using the Kolmogorov-Smirnov (KS) test. For normally distributed data, comparisons were made between groups using unpaired t-tests. For nonnormally distributed or categorical data, comparisons between groups were made using χ2 test. Statistical significance was set at P < 0.05. Statistical calculations were made using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, CA; available at: https://www.graphpad.com/).

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