TEST OF EXOCRINE PANCREATIC FUNCTION BREATH TEST

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1 Institute of Clinical Biochemistry & Laboratory Diagnostics 1st. Medical Faculty Charles University, Prague General Faculty Hospital,, Prague Kocna P., Vaníčková Z., Krechler T., Lukáš M.,, Doseděl J. TEST OF EXOCRINE PANCREATIC FUNCTION 13 C-MTG BREATH TEST Advances in pancreatology, KC Brno - April 23, 2004

2 Motto: if only we had simple, cheap and reliable test of exocrine pancreatic function... 2 PRIMARY DIAGNOSTICS of CHP FECAL ELASTASE SECRETIN PANCREOZYMIN PATINETS FOLLOW - UP NBT-PABA ALTAB TEST LUNDH TEST BREATH TEST 13 C-HIOLEIN CHP GRADING, CLASSIFICATION SIFICATION FECAL CHYMOTRYPSIN QUANTITATIVE MONITORING of FAT - 72 HRS. SUBST. THERAPY INDIRECT PANCREOLAURYL BREATH TEST 13 C-MTG DIF. DIAGNOSTICS of MALABSORPTION

3 DIRECT PZS TEST SECRETIN PANCREOZYMIN FECAL ELASTASE WITHOUT STIMULATION PABA, 13C-MTG STIMULATING MEAL INDIRECT STIMULATION AMYLASE LIPASE TRYPSIN BICARBONATE FECAL ELASTASE ENZYMES FROM THERAPY/DRUGS WITH mab NO REACTION LIPASE LIPASE ENZYME THERAPY LIPID HYDROLYSIS TEST, SUBSTRATE 3 DIRECT RESPONSE TO STIMULATION SECRETORY CAPACITY GRADING CHP DIGESTIVE FUNCTION OF (LIPID) DIGESTION

4 INDIRECT TEST - ALTAB/ 13 C MTG BREATH TEST TEST PROCEDURE STANDARD TEST MEAL TEST SUBSTANCE mg ALTAB/ 250mg 13 C-MTG 6 HOUR COLLECTION OF URINE/BREATH SAMPLES TEST PRINCIPLE CHYMOTRYPSIN LIPASE (Ac) - Tyr - PAB 13 C - MTG TEST ANALYTICS DETERMINATION OF SERUM LEVEL AND URINE OUTPUT MEASUREMENT OF HPAB/ 13 C IN BREATH SAMPLES CALCULATION OF % OUTPUT RATIO 4

5 13 C - BREATH TEST OF EXOCRINE PANCREAS SUBSTRATE SELECTION 13 C - TRIOLEIN 13 C - HIOLEIN 13 C - MIXED TRIGLYCERIDE 13 C - CHOLESTERYL OCTANOATE 13 C - TRIPALMITIN 13 C - TRIOCTANOIN 13 C - STARCH STEATORRHOEA > g/day INTRALUMINAL LIPOLYSIS PANCREATIC LIPASE SPECIFIC LIPASE OUTPUT < 90 ku/h PANCREATIC CHOLESTEROL ESTERASE STEATORRHOEA > 11 g/day FAT MALABSORPTION PANCREATIC DAMAGE, FIBROSIS > 30% AMYLASE SECRETION < 10% 5

6 13 C-MTG METABOLIC PROCES PANCREATIC LIPASE 13 CO 2 IN BREATH O 1,3 DI - STEAROYL CH 2 -O -C -(CH 2 ) 16 -CH 3 O CH - O - 13 C-(CH 2 ) 6 -CH 3 O CH 2 -O -C -(CH 2 ) 16 -CH ( 13 C) - OCTANOYL LIVER β - OXIDATION 6

7 TEST PROCEDURE TWO SAMPLE BAGS AFTER FASTING STIMULATION MEAL 4 CRISP SLICES, MAIZE WITH FIBRES (WITHOUT CHOLESTEROL, GLUTEN-FREE) 2 x 10g RAMA (VEGETABLE FAT WITHOUT MILK PROTEINS) TEST SUBSTANCE ADMINISTRATION - 250mg 13 C-MTG STIRRED INTO VEGETABLE FAT HOURLY BREATH-BAG BAG SAMPLING (1-6 hr) h TEST ANALYTICS DOB MEASUREMENT OF EACH SAMPLE 13 CO 12 2 : 1 2 CO 2 v T SAMPLE x AGAINST T 0 (DOB = Delta Over Baseline) T x 13 C-MTG BREATH TEST EVALUATION OF PANCREATIC INSUFFICIENCY BSA CALCULATED (BASED ON WEIGHT, HEIGHT ONLY) BMR AND CO 2 PRODUCTION CALCULATION 7 CUMMULATIVE RECOVERY FOR 6 HOURS CALCULATION

8 ISOMAX 4000 BREATH TEST ANALYSER 60,000 50,000 40,000 ANALYSIS OF 13 C: 12 C RATIO QUALITY CONTROL IRMS x IR, 10 CYCLES MEAN DOB = 5,4 % 30,000 20, , ANALYSIS REPEATED 4x CONSTANT RANGER ± 0,2 DOB 0,000-10,000 0,000 10,000 20,000 30,000 40,000 50,000 60,000-10,000

9 90 ISOMAX C RECOVERY CALCULATION PrCO 2 BSA = BSA * 300 mmol/h BSA = W^0,5378 W * H^0,3963 * 0, body surface (weight, height) only PrCO 2 BMR = BMR * 2,49 mol/d BMR = αw W + βh H + γ α, β, γ = constants for age, sex body surface (weight, height) age & sex corrected FUNCTIONAL TESTS AVERAGE DIFFERENCE = 27.1 % RANGE = % 9 PrCO 2 BSA PrCO 2 BMR

10 13 C-MTG BREATH TEST REFERENCE VALUES,, CUT- OFF VALUE Published studies with 13 C-MTG breath tests defined cut-off value for CHP diagnosis to cpdr 22% - 23% In these studies were cpdr calculated by body surface - BSA Mathematical approximation to use of BMR index mean differences BSA x BMR is 27,1% (n = 150) cut-off value is 28,64 % = 22,5 (BSA) * 1,271 (BMR) The lower limit of reference range determined with group of 23 subjects without CHP mean value cpdr in NON-CHP is 53,31, SD = 11,71 cut-off value is 29,89 % = x - 2SD (23 NON-CHP) 10

11 13 C-MTG BREATH TEST 11 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0,000 CUMMULATIVE RECOVERY 13 CO 2 in % NORMAL ABNORMAL FECAL ELASTASE µg/g cut - off = 29 %

12 8,000 7,000 6, C-MTG BREATH TEST DOB VALUES 13 CO 12 2 : 1 2 CO 2 in AFTER 250mg MTG NORMAL FECAL ELASTASE µg/g 5,000 4, ,000 2,000 1,000 0,000 ABNORMAL

13 13 C-MTG BREATH TEST x FECAL ELASTASE cpdr MTG (%) 80,0 70,0 60,0 50,0 40,0 30,0 100 µg/g CUT-OFF FELA: : 200 µg/g NORMAL CHP-A CHP-B CHP-C1 C1 CHP-C2 C2 CHP-C3 C3 NON-CHP CUT-OFF MTG: : 292 % 20,0 10,0 ABNORMAL MTG & FELA AGREEMENT 76.1 % (67/88) ) CHP 13 0, FELA µg/g

14 13 C-MTG BREATH TEST x FECAL ELASTASE cpdr MTG (%) 80,0 70,0 100 µg/g CUT-OFF FELA: : 200 µg/g NORMAL NON-CHP 60,0 50,0 40,0 30,0 CUT-OFF MTG: : 292 % 20,0 10,0 CHP TYPE C3 14 0, FELA µg/g

15 13 C-MTG BREATH TEST x FECAL ELASTASE cpdr MTG (%) 80,0 70,0 100 µg/g CUT-OFF FELA: : 200 µg/g CHP-A 60,0 50,0 40,0 30,0 CUT-OFF MTG: : 292 % 20,0 10,0 15 0, FELA µg/g

16 cpdr MTG (%) 80,0 13 C-MTG BREATH TEST x FECAL ELASTASE 100 µg/g CUT-OFF FELA: : 200 µg/g 70,0 60,0 50,0 CHP-B CHP-C1 C1 40,0 30,0 CUT-OFF MTG: : 292 % 20,0 10,0 16 0, FELA µg/g

17 13 C-MTG BREATH TEST x FECAL ELASTASE NON CHP-A CHP-B CHP-C1/2 CHP-C3 17 FREQUENCY OF CASES FELA < 100 µg/g & 13 C-MTG > 29%

18 18 EVALUATION OF EXOCRINE PANCREATIC FUNCTION Breath test 13 C-MTG provide us the complex evaluation of digestive processes - lipid digestion cpdr value of 13 C-MTG is the cummulative value, covering the exocrine pancreatic function + substitution therapy Cut-off value of cpdr 13 C-MTG, lower limit determined by mathematical approximation as well using a control group is identical - 29% Interpretation of 13 C-MTG include cummulative output - cpdr, maximal DOB value - DOB max, time to get of maximal DOB - DOB time, and the kinetics - curve type Combination of both tests covering various aspects - 13 C-MTG breath test and fecal elastase 1 could be recommended for evaluation of exocrine pancreatic function

19 (post)motto: simple, cheap and reliable test of exocrine pancreatic function we have not, HOWEVER FOR EVALUATION OF EXOCRINE PANCREATIC FUNCTION FECAL ELASTASE-1 ASE-1 & 13 C-MTG BREATH TEST IS VALIDATED & AVAILABLE 19 THANK YOU