Table of Contents

HK J Paediatr (New Series)
Vol 4. No. 1, 1999

HK J Paediatr (New Series) 1999;4:10-15

Original Article

Lactose Malabsorption by Breath H2 Test in Chinese Children

FHW Wong, CY Yeung, AYC Tam, KW Fung


Abstract

280 Chinese school children were investigated for lactose malabsorption by the breath hydrogen (H2) test. A modified anaesthetic bag system was developed to obtain the end-expiratory fraction of the expired air for the test. This has proven to be a highly efficient equipment to obtain the end-expiratory portion of a single breath from children. An oral lactose load of 1 gm/kg body weight was used, and the response in the rise of breath H2 was studied. The results showed two children populations, with an apparent cut-off point of 20 ppm which is the conventional criteria for distinguishing the lactose-absorbers from the malabsorbers, with the latter demonstrating higher breath H2 responses. Blood glucose profile studies have also validated the breath H2 test to be useful in identifying lactose malabsorption in children. The frequency of lactose malabsorption in Chinese children as inferred by the breath H2 test was found to rise from 21% at 3-5 years to over 57% beyond 6 years of age. Milk produced less breath H2 than equivalent amount of aqueous lactose in the same children studied.

Keyword : Breath H2 test; Chinese children; Lactose malabsorption; Milk versus pure lactose


Abstract in Chinese

Hydrogen (H2) is one of the intestinal gases produced by colonic bacterial fermentation. A significant proportion of the H2 produced is transported to the lungs via the blood stream and expired in the breath.1 Generation of H2 upon the entry of unabsorbed carbohydrate into the colon occurs rapidly, it may appear in the breath within 5 minutes.2 In general, an increase in breath H2 of more than 20 ppm above the basal level indicates biologically significant malabsorption.1-4

Lactose malabsorption is a common condition in adults especially among the Orientals,5-6 American Indians,7 Blacks8-9 and in some Caucasians.10-11 It usually does not occur in infancy but gradually appears at different ages in childhood. It appears early at 2-3 years in the American Indians12 and 3-5 years in Japanese.13 Among Finnish children,14 lactose malabsorption does not occur until late in teenage. Apparently there is significant variation among different races and different people. We conducted a field study on the breath hydrogen response to lactose to determine the occurrence of lactose malabsorption in Southern Chinese children.

Materials and Methods

(A) Selection of subject

280 Southern Chinese children were included in this study. They were all healthy school children from a primary school and a kindergarten in Hong Kong and their ages ranged from 3 to 12 years. Written informed consent was obtained from their parents. Information regarding their health and body weight were recorded and assessed before performing the breath H2 tests. Children suspected of gastrointestinal infection or having taken antibiotics within four weeks' before the tests were excluded from the study.

(B) Collection of End-expired Air

A 1-litre anaesthetic bag (Hudson Co.) with its tip cut and replaced by an auto-sealed septum (SU-850, Gallenhamp) was connected via a one-way valve to a T-joint (I.M.V. Manifold, Hudson Co.), one end of which was attached with a septum and the other end connected via another one-way valve to a disposable mouthpiece (Fig. 1). Each child was asked to blow forcefully into the mouthpiece to inflate the bag until he or she had completely exhaled. The end-expired fraction of the exhaled air was trapped by the two one-way valve arrangement (about 35 ml) and sampled immediately at the septum on the T-joint with an air-tight glass syringe (Dovebrand, Shanghai).

Fig. 1 An End-Expiratory Air Sampling System

The system consists of a 1-litre anaesthetic bag adapted with a T-joint. Note the direction of airflow from a single breath with the end-expiratory portion trapped between the two one-way valves of the T-adaptor.

(C) Test Procedure

The breath H2 test was performed at 9.00 a.m. in the morning after an overnight fast. Lactose 1 g/kg body weight in 200 ml solution was used as the test meal. End-expired samples were collected in duplicate before lactose administration, and again at 105-150 minutes afterwards, using the same anaesthetic bag system. Such two-point test has been used in several recent field studies.15-18 Earlier we had also conducted a preliminary survey on 85 hospitalised children which showed that over 84% of the peak H2 excretion occurred at 130 ± 20 min. after lactose19 indicating the time chosen for the study was appropriate. Samples collected were stored in an air-tight 2-ml all-glass syringe (Dovebrand, Shanghai) fitted with a teflon three-way stopcock. Such device had been shown to be stable for H2 and CO2 storage up to 16 hours, with retentivity of 85% and 91% respectively.19

The H2 content in the breath samples was measured by the Shimadzu GC 8 APT Gas Chromatograph equipped with a thermal conductivity detector (Shimadzu Co., Japan). 0.25 ml sample was injected into a 6-ft x 0.125-in o.d. stainless steel molecular sieve (5A, 60/80 mesh) column with a gas-tight syringe (Hamilton Co. Ltd., USA). H2 was separated at a column temperature of 70°C, at filament current of 70 mA and an argon gas carrier flow of 54 ml/min. The time needed for analyzing a sample was about 3 minutes. The CO2 content was analyzed in another 0.25-ml sample using a silica gel column (60/80 mesh), at the same instrumental conditions as above.

(D) H2 and Blood Glucose Profile Studies

Consent was obtained in 30 (10.7%) of the children for a second study for a 4-hour H2-Profile test. The same dose of 1 gm lactose/Kg was used for each profile testing. Sixteen of them had been found to have raised breath H2 response from the initial screening test. Twenty-two of the children also gave consent for tests on blood glucose changes simultaneously with the breath H2 analysis. Capillary blood samples were collected immediately after each breath collection, and the glucose concentration was determined with the Beckman glucose Analyzer (Beckman Co., USA).19

(E) Milk Vs Aqueous Lactose Study

Eight children were tested for 4-hour breath H2 response on two consecutive days. They were given aqueous lactose on one day and equivalent amount of lactose in formula-milk (S-26) on the other at random sequence.

Result

A total of 974 breath samples were collected and analyzed. The H2 content measured was normalized to alveolar CO2 using the Niu's approximation 20 ppm. The coefficient of variation (CV) of intra-individual samples for normalised H2 was 8.59 ± 3.00%. The results are shown in the Figures and Table.

A. Breath H2 Response

The distribution of the rise in normalised breath H2 above the basal, (NRBH) as expressed as their log values, appears to compose of two populations slightly overlapping on each other. The two intersects at log 1.26 which is about 20 ppm H2 (Fig. 2), coinciding with the conventional criteria for diagnosing lactose malabsorption.2-4 The curve on the left probably represents the lactose absorbers. The fasting breath H2 concentration of the 280 children showed an arithmetic mean of 8.20 ± 6.25 ppm, ranging from 2.60 to 48.2 ppm.

B. Lactose Malabsorption in Children

A typical frequency distribution curve for an individual age group is shown in Fig. 3. The occurrence of a distinct bi-nodal distribution implies that lactose malabsorption is a common trait in the Southern Chinese children population. Table summarizes the frequency of lactose malabsorption in the children's studied, which was 56.8% as indicated by the lactose breath H2 test. Between 3 and 5 years of age, lactose malabsorption occurred in about 21% of the children. This increased to 57% at age 6, and continued with much slower increase thereafter. No significant difference was observed in the occurrence of lactose malabsorption between boys and girls, though a slightly higher value was obtained in girls.

Fig. 2 Histogram of Rises in Log Values of Normalised Breath H2 in 280 Chinese Children

Note the 2 overlapping distribution curves with an apparent dividing point at log 1.26 which is about 20 ppm, the conventional cut-off level for diagnosing sugar malabsorption. 2 children with 110 ppm and 126 ppm above basal respectively are not shown in this figure.

 

Fig. 3 The Frequency Distribution of Breath H2 Responses in the 7-Year Old Group

Note the bi-nodal distribution.

C. H2 and Blood Glucose Profile

All the 16 children who showed a raised breath above 20 ppm at the initial screening had reported intolerant symptoms after lactose-containing food such as abdominal pain, bloating or diarrhoea. All of them gave increased breath H2 test results on follow-up, with rise of NRBH ranging from 29.5 to 112.3 ppm. Their fasting H2 concentrations were above 12.5 ppm. However, only 11 of them complained of intolerant symptoms on receiving the lactose test meal. All of them showed flat blood glucose response compatible with lactose malabsorption, as illustrated in a 12 year old in Fig. 4.

One child who was previously found to have a low breath H2 response had eaten chewing gum shortly before the profile test. He was found to have a basal concentration above 40 ppm. Subsequent monitoring of his breath H2 after lactose administration, however, showed a progressive drop to 12 ppm by 2 &189; hr. Apparently the chewing gum might be the cause of his abnormally high baseline value. The 5 other children who had an initial low breath H2 response continued to show similarly low H2 on the profile tests. All 6 children in this group had normal blood glucose rises above 1.2 mmol/l after lactose, compatible with appropriate lactose digestion and absorption. The high correlation of the results indicates that the breath H2 response to lactose is a highly sensitive test for detecting lactose malabsorption.

Fig. 4 Breath H2 and Blood Glucose Responses to oral lactose in a 12-year-old Boy

Note the H2 levels were >20 ppm from 1&189; hours onward all through the test. This was associated with a flat blood glucose curve. Features are compatible with lactose malabsorption.

D. Milk Versus Fresh Lactose Solution

As can be noted from Fig. 5 and 6, there are significant differences in the breath H2 responses between milk and fresh lactose solution as the test meal. Aqueous lactose resulted in much higher peak rises in breath H2 (mean 33.66 ± 6.83 ppm versus 25.09 ± 4.73 ppm in milk; paired t=3.82; p=0.07 or p<0.01) and shorter time to reach the peak (2.81 ( 0.19 hours versus 4.69 ± 0.33 hrs. for milk; paired t=5.00, p=0.002 or p<0.005).

Fig. 5 Dietary effect on Peak Rise of Breath H2 in 8 children

Note the 4-hours breath H2 profile test showing significantly higher peak values with aqueous lactose than with milk (S-26, Wyeth).

 

Fig. 6 Dietary effect on Peak Rise of Breath H2 in 8 children

Note the significantly shorter time to reach the peak with aqueous lactose than with milk.

Discussions

The sampling bag system we developed is simple to operate. It requires minimal intelligence or cooperation of the subjects studied and it generates no discomfort to the children. A single big breath to blow up the anaesthetic bag via the T-adapter is all that is required. The samples so obtained corresponded to 72-86% of the alveolar air using alveolar CO2 as the reference. It is apparently a very convenient method for field studies involving end-expiratory air sampling like ours. We have encountered no difficulties even in young children of only 3 years old. The principles of operation of our device is similar to the blowout system reported previously21 but samples obtained with our equipment were much closer to the alveolar concentration.

Our study has validated the conventional criteria for diagnosing lactose malabsorption using the breath H2 test. A rise of over 20 ppm of breath H2 above the basal after lactose ingestion was associated with a flat blood glucose curve and is indicative of malabsorption of the sugar.2-4 Normalisation of the breath H2 responses did not alter very much the cut off point for diagnosing lactose malabsorption. Although some workers3,22 have suggested that a 10 ppm rise was sufficient for a diagnosis, indeterminate results were obtained when compared with the blood glucose tests. Moreover, none of the children who showed breath H2 rise within 10-20 ppm had intolerant symptoms during the study. 10 ppm rise is apparently an inappropriate level for a diagnosis.

Lactose deficiency and lactose malabsorption is a physiologic phenomenon. Ninety percent of the world's adult populations are probably lactase deficient, but lactase activities start to decreases at different ages in different races, usually some years after weaning. In some Caucasians, reduced lactase activities appear around 5 years.2,3 In Japanese, lactose malabsorption occurs earlier;13 30-58% of children between 3 and 5 years is already malabsorbing and the frequency increases to 86% at 6 years of age. In Finland, hypolactasia may not express until 15-20 years of age.14 Apparently, genetic factors and continued lactose intake after weaning may contribute to sustained lactase activities in some people. Flatz24 proposed a "temporal gene theory" which suggested that a lactase "switch" or "shutoff" occurs during early childhood. More investigations about this gene regulation in "shutting off' the lactase switch in different races are needed to improve our understanding of the mechanism in initiating lactase deficiency in adults.

Only scanty data are available on the huge Chinese population of 1.3 billion. Earlier studies on adults have reported a lactose malabsorption prevalence rate of 88-95%.5-6 In a study of Chang et al,25 a high prevalence rate of lactose malabsorption among the children in Taiwan was also reported. As infant feeding habits and weaning foods used are very different in the southern Chinese,26-27 reduced lactase activities may also occur at different ages from different parts of the vast Chinese country. We have provided information on lactose malabsorption as diagnosed by the breath H2 response test in the southern Chinese children of Hong Kong. Apparently, the pattern of lactose-malabsorption in the Southern Chinese children of Hong Kong does not differs significantly from that some of the Northerners reported from Taiwan.25 In the Chinese neonates however, lactose malabsorption is not a significant clinical problem.28-29

The pattern of increasing frequency of lactose malabsorption with ages of the children indicated that 3-5 years of age may be an important transitional period during which lactose-absorbing ability decreases very rapidly. By 6 years of age, lactose malabsorption reached a high level of 57% and the rate continues to increase (Table). Of the 165 lactose malabsorbers, 34 of them complained of intolerant symptoms during the test, and one had diarrhea within 30 minutes of lactose administration. However, on questioning, over 109 of the malabsorbers had felt discomfort on drinking even a glass of milk. As the amount of lactose in the milk (about 10 gm in 8 oz) is much less than the load used for the H2 breath test, the discomfort felt was probably caused by factors other than the lactose alone.

In this study, significantly higher fasting H2 values were observed in the lactose malabsorbers than in the absorbers. There is a significant correlation (r=0.71836; p<0.0001) between the rise in normalised breath H2 (NRBH) and the basal values. The mean ± SD values of the normalised basal H2 (NBBH) which were associated with rises greater than 20 ppm was 10.67 ± 7.68 ppm. These contrast those NBBH with rises less than 20 ppm with their mean ± SD values of only 4.78 ± 1.49 ppm. The difference was found to be statistically significant (p=0.041). Such basal H2 in the breath is generally thought to be due to the fermentation of glycoproteins from desquamated intestinal cells released in the process o normal villous turnover, or residual sugars in the colon.28

The traditional application of breath H2 measurement has been to examine the absorptive responses to carbohydrate, and emphasis has generally been focused on reducing the fasting breath H2 concentrations to maximize the sensitivity. Recently, some workers have suggested some intrinsic diagnostic significance of the basal level of H2 in the preprandial expired air.31-34 The high correlation of rise in breath H2 (NRBH) with the basal breath H2 (NBBH) as found in our study suggests some productive value to the fasting H2 concentration. Similar observation was made in a recent study conducted in Hong Kong. The frequency of lactose malabsorption utilizing breath H2 analysis similar to our study was also similar30 to our findings.

The much larger variation of the fasting H2 concentrations (mean value of 10.67 ± 7.68 versus 4.78 ± 1.47 ppm) observed in the malabsorbers than the absorbers may suggest a wide variety of etiology in lactose malabsorption.33 The peristaltic rhythm of the individual and the size of his anaerobic fecal flora,35 along with the balance between H2-producing and H2-consuming microbes in the large bowel34 constitute the endogenous factors conditioning the fasting breath H2 levels. Dietary factors related to the amount of carbohydrates, both digestible18,35-38 and nondigestible,39 in the previous day's intake are exogenous modulation of the fasting breath H2 in the pulmonary gas. If the preprandial H2 content in the breath is used as a diagnostic variable in breath H2 analysis, various factors conditioning the fasting level mentioned above must be taken into consideration.

Our observation of significant differences between formula milk and aqueous lactose in breath H2 responses is very interesting. The lactose solution we used was generally hypertonic. This might induce intestinal hurry thereby increasing the amount of undigested sugar reaching the colon. This could explain the significantly higher peak rises in breath H2 and the shorter time to reach the peak with aqueous lactose (Fig. 5 & 6) as shown in our study. It has also been known for some time that fat and proteins may slow down gastric emptying.40 Prolonged gastric retention of lactose when offered as milk would reduce the rate of its deliverance to the colon.38,41-42 Alternatively, the slower deliverance of the substrate to the intestine could increase the duration of contact between the lactose and the available lactase, resulting in increased hydrolysis and less malabsorption.43 The presence of other food components may also interfere with the bacterial fermentation of lactose.41 More detailed studies are obviously needed to clarify the mechanism for the difference in the production of H2 from an equivalent amount of lactose observed between milk and aqueous solution.

The modified anaesthetic bag system we developed has been proven to be a simple and highly effective equipment to obtain the end-expiratory fraction of exhaled air. Southern Chinese children demonstrated increasing prevalence of excessively high breath H2 From 3 years onward 21% were malabsorbing reaching a level exceeding 57% beyond 6 years. Such pattern is similar to those reported for Northern Chinese children. Milk produces significantly less breath H2 responses than equivalent amount of aqueous lactose given to the same children.

Acknowledgment

We thank Mrs. Helen Yeung, the Principal of Li Chi Ho Primary School for her help in organising the children for this study. We also thank the school children, the resident and technical staff of our department for their help in the fieldwork.


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