Sample Collection.

For children under the age o f 4yrs a cut down naso-gastric tube was passed through the nostril to the back o f the throat. This nasopharyngeal tube was attached to a three-way stop valve on the end o f a 60ml syringe. End expiratory air was thus withdrawn by

6,2.4 Analysis.

The end expiratory air was retained in the syringe by the turning o f the three-way valve. Samples were then analysed directly using a hydrogen monitor (Gas M easurement

, b

Instruments Ltd. Scotland, see 3.7). A rise o f more than lO.OOppm (parts per million) above the baseline value was considered to be significant and registered as the gut transit time. Patients with a rise o f >20.00ppm and a transit time o f < 30 minutes, were

considered to have small bowel bacterial colonisation.

6.2.5 Statistics.

All pre and post load breath hydrogen data obtained were compared, with respect to both aetiologic conditions and small bowel biopsy results. Significant differences were

determined by the Wilcoxon's non-parametric rank sum test (Wilcoxon 1945) and significance assumed at p<0.05 in all cases (Hayslett 1973).

6.3 Results.

All the raw data obtained for this test are detailed in Appendix III.

Five o f the 40 (12.20%) o f the patients tested showed no significant increase in breath hydrogen levels fi*om the baseline after four hours and therefore were classified as non-hydrogen producers. N o relationship was found between gut transit time and age (Fig 6.2). The frequency distribution o f gut transit time results was found to be

non-Gaussian thus for the calculation o f the mean gut transit time and normal reference value the logarithmic equivalent o f the data was used (Hayslett 1973). This gave a median (interquartile range) gut transit time, for this population o f 90.00 (30.00-97.50) minutes and a "normal" range o f 23.22-166.02 minutes.

The sensitivity o f the breath hydrogen test, was determined by recording the percentage o f children with an abnormal biopsy and consequent rapid or extended gut transit time. This was found to be 50.00%. Test specificity, calculated as the percentage o f children who had a normal small bowel biopsy and a normal gut transit time, was found to be 85.71%.

On 180 150 ? 120

ee

I

### ee

ee

ee e

The patients were then separated into categories according to their aetiologic conditions and mean gut transit times compared to establish whether there w ere any significant differences existed between the groups (Table 6.1 and Fig 6.3).

Cow's Milk Protein Intolerance.

This group consisted o f eight children. Three o f these children (group A) had been on a restrictive milk free diet and thus were being seen as follow-up cases, whilst three children (group B) had been placed in this group on the basis o f their past medical history and presenting symptoms. Two children were classified as non-hydrogen producers (no detectable increase in baseline hydrogen values observed after 4 hours). Small bowel biopsy data w ere available for all eight children. Details o f the children's breath hydrogen results with respect to their small bowel biopsies are shown below.

Group A (n=3)

;

normal transit time (n=3)

I

normal biopsy (n=3)

Group B (n=5)

normal transit time (n=2) rapid transit time (n=l)

Table 6.1. Lactulose breath hydrogen test data.

w oe

Aetiolo^iç

ÇrOVD

Qut Transit Time (mins)

median trangel

normal SBB abnormal SBB

cmpi 8 60, 90, 120* 60.00 (30-90)

coeliac disease 5 90 & 120 30, 30 & np*

si colonisation 4 90 & np 90^

toddler's diarrhoea 2 6 0 & 9 0 na

27unknown aetiology 21 90 (30-180) 60 (30-150)

cmpi = cow's milk protein intolerance, si = small intestinal, SBB = small bowel biopsy, n/a = all children with toddler's diarrhoea had normal SBBs. np = non-producer ^ only one child had an abnormal biopsy in this category.

* Raw data is given for categories with <4 subjects.

N VO

I

I

I

normal gut transit t i m e --- rapid gut transit t i m e --- small intestinal colonisation - 150 100 /# 50 0 30 0 60 90 120 150 180 210 Time (mins)

Fig.6.3. The graph shows characteristic patterns for the excretion of end expiratory breath hydrogen in a normal individual (a), a child with rapid gut transit time (b) and a child with small intestinal colonisation (c).

Coeliac Disease.

This group consisted o f five children. One child (Group A) was on a restrictive gluten-free diet at the time o f testing and was therefore being seen as a follow-up case. F our children (Group B) were placed in this category as a result o f their presenting symptoms and previous medical history. The child in Group A had both a normal gut transit time and a normal small bowel biopsy. One child in Group B was a non-hydrogen producer. The results o f the other children in Group B are shown below.

Group B (n=4)

normal biopsy (n=I)

i

normal transit time

abnormal biopsy (n=3)

non hydrogen producer (n=l) rapid transit time (n=2)

Toddler's Diarrhoea

This group consisted o f tw o children who had normal small bowel biopsies but suffered from continuous diarrhoea. Both children had normal gut transit times.

Small Intestinal Colonisation

This group consisted o f four children, three (Group A) with bacterial colonisation and one (Group B) with both bacterial and Giardia infestation. The diagram below shows the breath hydrogen results for children in this category.

Group B (n=l)

abnormal biopsy

non hydrogen producer

Failure to Thrive of Secondary or Unknown Origin

The twenty-one children placed in this group had presented with gastrointestinal symptoms that were either secondary to a previously diagnosed condition, or of an unknown aetiology. Small bowel biopsy results were available for fifteen children. Ten children had abnormal biopsies (Group B) and five children had normal small bowel biopsies (Group C). The distribution of gut transit times with respect to mucosal damage are shown below

Group A (n=6) (no biopsy results)

i

normal transit time (n=6)

Group B (n=10)

i

rapid transit time (n=4) normal transit time (n=5) non-hydrogen producer (n=l)

Group C (n=5)

I

Intra and inter group comparisons, of gut transit time data with respect to small bowel biopsy results showed the following:

(i) Children with cow's milk protein intolerance have gut transit times that are significantly shorter than patients with failure to thrive o f secondary or unknown aetiology regardless o f their biopsy result.

(ii) Children with coeliac disease and abnormal small bowel biopsies have significantly shorter gut transit times than children with abnormal biopsies in all the other aetiologic groups.

The median (interquartile range) preload and maximum breath hydrogen excretion values were, 3.5 (2.5-8.0ppm) and 29.5 (10-59.5ppm) respectively. High fasting breath hydrogen values were recorded for children with toddler's diarrhoea (15.0 and 20.5ppm) and two children with small intestinal colonisation (17.0 and 33.0ppm). Whilst the highest maximum excretion values was found in a child with small intestinal colonisation (ISl.Oppm).