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CHARACTERIZATION OF IRRITABLE BOWEL SYNDROME USING COLORECTAL DISTENSION AND BARORECEPTOR SENSITIVITY

R Spaziani, K Redmond, A Bayati*, H Larsson*, SM Collins, MV Kamath
McMaster University, Hamilton, Ontario; *AstraZeneca R&D, Molndal, Sweden

Lack of disease specific biomarkers in Irritable Bowel Syndrome (IBS) has made its management difficult. Assessment of autonomic nervous system (ANS) by baroreceptor sensitivity (BRS; change in R-R/change in BP) has identified low BRS in IBS suggesting vagal dysfunction.
AIMS: To develop a novel classification method to characterize IBS based on colorectal distension (CRD) studies and BRS.
METHODS: After a 20-min baseline, a barostat-controlled rectal bag (max. volume 863 mL) was distended (0.5 mmHg/s), to a max pressure of 70 mmHg, or 50% discomfort (whichever came first), and maintained in this tonic state for 3 mins. A 20-min recovery period was recorded. BRS was computed during baseline, tonic, and recovery periods using 3 or more increasing sequences within continuous HR and systolic BP time series. Group means were compared using Student's t-test. A sensitivity index (SI) was developed using CRD variables and cluster analysis (Spotfireо Decision site^TM 8.1.1).
RESULTS: 98 healthy volunteers (HV; 34▒12 yrs, 52F) and 38 IBS patients (39▒11 yrs, 35F) were studied. Three CRD variables (discomfort threshold pressure, max pressure, and max discomfort response) clustered subjects into 3 groups: HS (Hypersensitive), NS (Normosensitive), hS (hyposensitive). 22 HS-HV (27▒8 yrs, 10F) and 10 HS-IBS (38▒9 yrs, 10F), 35 NS-HV (31▒11 yrs, 19F) and 12 NS-IBS (35▒13 yrs, 9F), 17 hS-HV (42▒11 yrs, 10F) and 0 hS-IBS subjects were characterized.

Table: BRS and SI

а Control BRS Base Control BRS Tonic Control BRS Post Patient BRS Base Patient BRS Tonic Patient BRS Post
HS 12.12▒2.36 9.39▒2.66** 11.95▒2.58 7.63▒2.23* 7.19▒2.17 7.31▒2.17*
NS 9.89▒2.49^з 8.19▒2.23** 10.89▒2.43 9.38▒2.47 6.70▒2.58** 9.43▒2.46*^,з
hS 7.53▒2.25^з,зз 6.45▒2.52^з,зз 7.48▒2.44^з,зз а а а
**p<0.05 vs. baseline; зp<0.05 vs. HS, ззp<0.05 vs. NS , *p<0.05 vs. HV

DISCUSSION: Based on 3 CRD variables, IBS can be classified as HS or NS. BRS was lowest in HS-IBS and highest in HS-HV and did not recover post-distension in HS-IBS compared with NS-IBS. Low BRS represents vagal dysfunction and correlated with the most sensitive IBS group. CRD and BRS allows for objective sub-classification of IBS.
Support: NSERC, DeGroote, AstraZeneca

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Table: BRS and SI
а	Control BRS Base	Control BRS Tonic	Control BRS Post	Patient BRS Base	Patient BRS Tonic	Patient BRS Post
HS	12.12▒2.36	9.39▒2.66**	11.95▒2.58	7.63▒2.23*	7.19▒2.17	7.31▒2.17*
NS	9.89▒2.49^з	8.19▒2.23**	10.89▒2.43	9.38▒2.47	6.70▒2.58**	9.43▒2.46*^,з
hS	7.53▒2.25^з,зз	6.45▒2.52^з,зз	7.48▒2.44^з,зз	а	а	а
*p<0.05 vs. baseline; зp<0.05 vs. HS, ззp<0.05 vs. NS , p<0.05 vs. HV