Phenotypic variation of colonic motor functions in chronic constipation

Abstract

Background & aims: Colonic motor disturbances in chronic constipation (CC) are heterogeneous and incompletely understood; the relationship between colonic transit and motor activity is unclear. We sought to characterize the phenotypic variability in chronic constipation.

Methods: Fasting and postprandial colonic tone and phasic activity and pressure-volume relationships were assessed by a barostat manometric assembly in 35 healthy women and 111 women with CC who had normal colon transit (NTC; n = 25), slow transit (STC; n = 19), and defecatory disorders with normal (DD-normal; n = 34) or slow transit (DD-slow; n = 33). Logistic regression models assessed whether motor parameters could discriminate among these groups. Among CC, phenotypes were characterized by principal components analysis of these measurements.

Results: Compared with 10th percentile values in healthy subjects, fasting and/or postprandial colonic tone and/or compliance were reduced in 40% with NTC, 47% with STC, 53% with DD-normal, and 42% with DD-slow transit. Compared with healthy subjects, compliance was reduced (P <or= .05) in isolated STC and DD but not in NTC. Four principal components accounted for 85% of the total variation among patients: factors 1 and 2 were predominantly weighted by fasting and postprandial colonic phasic activity and tone, respectively; factor 3 by postprandial high-amplitude propagated contractions; and factor 4 by postprandial tonic response.

Conclusions: Fasting and/or postprandial colonic tone are reduced, reflecting motor dysfunctions, even in NTC. Colonic motor assessments allow chronic constipation to be characterized into phenotypes. Further studies are needed to evaluate the relationship among these phenotypes, enteric neuropathology, and response to treatment in CC.

Figure 1

CONSORT Diagram.

Figure 2

Comparison of colonic compliance (Pr₅₀) among categories. Among patients without DD, Pr₅₀ was lower in STC than NTC. However, among patients with DD, Pr₅₀ was comparable in DD-NTC and DD-STC. The horizontal line is the 10^th percentile value in healthy subjects.

Figure 3

Normal fasting, postprandial and post-neostigmine tonic and phasic colonic motor activity in a patient with STC. Observe reduced balloon volume, reflecting increased colonic tone, after a meal and after neostigmine. Manometry showed increased phasic pressure activity in the sigmoid colon after a meal and also in the descending colon after neostigmine. The principal component analysis revealed a high score for factor 2.

Figure 4

Impaired colonic tonic contractile responses to a meal and neostigmine in a patient with STC. In contrast, manometry revealed increased fasting and postprandial phasic pressure activity. The principal component analysis revealed a high score for factor 1.