Lactose Breath Test: Possible Strategies to Optimize Test Performance, Accuracy, and Clinical Impact

Abstract

Lactose malabsorption (LM) refers to the incomplete absorption of lactose in the small intestine, resulting in the arrival of ingested lactose in the colon, which can give rise to symptoms defined as lactose intolerance (LI). The lactose breath test (LBT), thanks to its low cost, availability, and noninvasiveness, is the most used diagnostic method. However, the LBT is a tedious tool, requiring prolonged involvement of patients, qualified staff, and infrastructure, of which the most time-consuming factor is the frequency and number of breath samples needed. Objectives: To simplify the current LBT methodology, compliant with the current guidelines' statements, by reducing the test duration or the number of breath samples, without compromising the test's accuracy. Methods: The results of the standard LBT were compared with two simplified tests: a "shortened" test, lasting three hours, with samples taken every 30 min; and a "five-sample" test, lasting four hours, with samples taken every hour. Patients were stratified into three grades of malabsorption (mild, moderate, severe) based on the amount of gas exhaled. A clinical severity score was introduced to assess the clinical relevance of LI using a specific questionnaire. Results: Among the 543 patients enrolled (F 71.5%, mean age 43.7 ± 17.6 yrs), 60.4% (328/543) tested positive for LM. A total of 70.5% (383/543) presented LI, with 32.1% of those being true intolerants (LI without LM). The shortened test demonstrated an accuracy of 93.9%, with a sensitivity of 89.9% and a false negative rate of 10.1% (33/328). The five-sample test showed higher accuracy and sensitivity than the shortened test (96.5% and 94.2%, respectively; p = 0.03) with a false negative rate of 5.8% (19/328). Of the 19 false negatives in the five-sample test, 95% (18/19) were categorized as mild malabsorbents. No statistical correlation was found between the clinical severity score and LBT results. Conclusions: The five-sample test, involving hourly breath measurements, is a reliable option for simplifying the LBT without significantly reducing the procedure's sensitivity.

Keywords: breath test; intolerance; lactose; malabsorption.

Figure 1

Test procedures of the three methodologies of lactose breath test. Each procedure was performed by administering 25 g of lactose. The standard test consists of nine breath samples, collected every 30 min up to 240 min (0, 30, 60, 90, 120, 150, 180, 210, 240). The shortened test consists of seven measurements, collected every 30 min up to 180 min (0, 30, 60, 90, 120, 150, 180), while the five-sample test consists of five measurements, collected every 60 min up to 240 min (0, 60, 120, 180, 240).

Figure 2

Flowchart of the study: from 549 subjects initially enrolled in the study, 543 patients were finally included in the analysis and lactose malabsorption was detected in 60.4% of patients. Abbreviations: H₂: hydrogen, CH₄: methane.

Figure 3

Correlation between Δ-ppm and AUC (a) for H₂ and (b) for CH₄. The Δ-ppm was calculated as the difference between the maximum value of ppm obtained during the test and the baseline value. The AUC was calculated from baseline to 240 min and expressed in arbitrary units of ppm/h. A statistically positive correlation was found between the Δ-ppm value and the AUC, both for H₂ and CH₄.

Figure 4

Waterfall plot of the Δ-ppm H₂ (a) and CH₄ (b) values in subjects with lactose malabsorption in the five-sample test. Horizontal lines represent the cut-off values of the three levels of malabsorption. Each vertical line represents a patient, the yellow lines indicate concordant results between the standard test and the five-sample test, while the blue lines indicate the false negative results obtained in the five-sample test. All the false negative results, except one positive for CH₄, fall into the mild grade of malabsorption category.

Figure 5

Clinical severity score. Clinical presentation was evaluated with a self-assessed questionnaire focused on symptoms experienced in the previous month. A score from 0 to 3 was assigned for each item: never: 0; monthly: 1; weekly: 2; daily: 3. Most patients reported a monthly occurrence of all the symptoms evaluated (pain, diarrhea, and bloating). Abbreviations. LM+: presence of lactose malabsorption, LM−: absence of lactose malabsorption.