Eric Shah, William D. Chey, Chris Almario, Brennan Spiegel Differences in lower and upper GI symptoms between individuals with irritable bowel syndrome with constipation and chronic functional constipation Eric Shah, William D. Chey, Chris Almario, Brennan Spiegel

Diagnostic criteria for functional diseases are not perfect constipation Diagnostic criteria: 2+ of: straining, hard BM, incomplete evacuation or blockage, manual maneuvers, <3 BM/wk 2) Use of laxatives 3) Insufficient for IBS Constipation predominant IBS Diagnostic criteria: Recurrent abd pain or discomfort and 2/3 of following: 1) Improvement with defecation 2) Sx onset with Δ in stool frequency 3) Sx onset with Δ in stool form Functional constipation and constipation predominant IBS can be defined using the Rome criteria as separate syndromes. However, not all patients fall precisely into one set of diagnostic criteria. Instead, we might be able to rationalize these syndromes not as distinct entities, but as phenotypes along a spectrum of disease. The Rome Model Spectrum of disease

Diagnostic criteria for functional diseases are not perfect Here, I’m showing you the results of a validation study of patients identified as having IBS by their PCP, with each overlapping circle representing a different diagnostic criteria group. We can see that the criteria each capture only a portion of the population. One explanation for the poor overlap is that there are been few prospectively enrolled studies to inform us about the symptom characteristics which could help better define these disorders. Engsbro AL, Begtrup LM, Kjeldsen J, Larsen PV, de Muckadell OS, Jarbøl DE, Bytzer P. Patients suspected of irritable bowel syndrome--cross-sectional study exploring the sensitivity of Rome III criteria in primary care. Am J Gastroenterol. 2013 Jun;108(6):972-80. doi: 10.1038/ajg.2013.15.

Study aims To evaluate the distribution of lower and upper GI symptoms in a nationwide sample of IBS and FC patients

Data source The platform used to generate our data was the mobile and web-based MyGiHealth, which offers a nationwide sample evaluating almost 70,000 US adults. This mobile platform allows patients to enter their data into a validated NIH PROMIS questionnaire, to standardize the assessment of gastrointestinal symptoms over the prior seven days and to then track their results over time and in comparison to their peers.

Data source Partnered with Cint®, a survey research firm. Recruited a representative sample of the U.S. general population. Recruitment quotas in place for: Age Gender Location (W, MW, NE, S) Participants were recruited in this large survey through Cint, a contract research firm, from the general US population according to recruitment quotas for age, gender, and location.

Deriving the GI PROMIS questionnaire Literature review Focus groups and qualitative data analysis After assembling the population, GI PROMIS scores were used to standardize our evaluation of symptoms. The key items in these scores were developed by prior authors by first conducting a literature review, and then using focus groups and qualitative data analysis to evaluate key phrases and language to finalize the PROMIS items into the final questionnaire. Final questionnaire

Deriving the GI PROMIS questionnaire GI PROMIS symptoms Abdominal pain Bloating Constipation Diarrhea Dysphagia GERD Incontinence Nausea Symptoms were broken down into eight broad primary gastrointestinal complaints, with individual survey questions tailored to patients experiencing these symptoms.

Sample GI PROMIS questions In the past seven days… How often did you pass very hard or lumpy stools? How much did hard or lumpy stools bother you? How often did you strain while trying to have bowel movements? How much did you usually strain while trying to have a bowel movement? How much did straining during bowel movements bother you? As an example,

Deriving the GI PROMIS questionnaire 40% (-1SD) 60% (+1SD) 0% 50% (average score) 100% Scores for symptom severity were assigned based on a percentile system, with a symptomatic patient with an average amount of severity, assigned a score of 50%. A score plus or minus 10% represented an increase or decrease by a standard deviation of 1.

Outcomes and Statistics Odds of having GI symptoms in IBS-C vs FC participants Symptoms severity based on GI PROMIS score OUTCOMES We assessed three main outcomes in this study. We first determined the odds of having GI symptoms in IBS-C versus FC, then assessed symptom severity using the GI PROMIS score, and finally assessed the overall raw prevalence of symptoms in our cohort. We conducted regression analysis to adjust for potentially confounding demographic variables. Prevalence of symptoms

Population characteristics 970 eligible adults 257 with IBS-C 713 with FC IBS-C FC Age 42.7±12.6 43.3±13.2 Female 77.5% 78.1% Race Non-hispanic white Non-hispanic black Hispanic Asian Other 77.8% 6.2% 9.5% 1.5% 5.1% 80.3% 6.5% 8.2% 1.9% 3.1% At least college graduate* 32.0% 42.1% Married/long term relationship* 62.6% 69.4% Employed or full-time 50.9% 51.0% Income 50k or greater* 48.1% 38.2% *p<0.05 by Pearson chi-square test of significance

Odds of GI symptoms with IBS-C versus FC Here are the results for our first outcome, evaluating the odds of having GI symptoms in IBS, with a higher odds going up favoring IBS, versus FC, with an odds less than one and going dwon. * * *

Odds of GI symptoms with IBS-C versus FC * * *

Percentile of lower GI PROMIS® symptom scores for FC and IBS-C No significant difference in severity of motility symptoms * p<0.001 * p<0.001 Moving to symptom severity,

Percentile of lower GI PROMIS® symptom scores for FC and IBS-C IBS patients have more severe non-motility symptoms than FC patients

Percentile of upper GI PROMIS® symptom scores for CIC and IBS-C

Prevalence of GI symptoms for FC and IBS-C Notice that abdominal pain is a common feature of functional constipation, but of course these patients do not have symptoms which are severe enough to meet Rome III criteria. We see that the IBS-C symptoms (represented in light gray bars on the left) have a similar distribution as those of functional constipation (represented in the stripedbars on the right), but that every symptom is somewhat amplified in IBS patients.

Prevalence of GI symptoms for FC and IBS-C Notice that abdominal pain is a common feature of functional constipation, but of course these patients do not have symptoms which are severe enough to meet Rome III criteria. We see that the IBS-C symptoms (represented in light gray bars on the left) have a similar distribution as those of functional constipation (represented in the stripedbars on the right), but that every symptom is somewhat amplified in IBS patients.

Prevalence of GI symptoms for FC and IBS-C Notice that abdominal pain is a common feature of functional constipation, but of course these patients do not have symptoms which are severe enough to meet Rome III criteria. We see that the IBS-C symptoms (represented in light gray bars on the left) have a similar distribution as those of functional constipation (represented in the stripedbars on the right), but that every symptom is somewhat amplified in IBS patients.

Prevalence of GI symptoms for FC and IBS-C Notice that abdominal pain is a common feature of functional constipation, but of course these patients do not have symptoms which are severe enough to meet Rome III criteria. We see that the IBS-C symptoms (represented in light gray bars on the left) have a similar distribution as those of functional constipation (represented in the stripedbars on the right), but that every symptom is somewhat amplified in IBS patients.

Conclusions Bloating is more severe/frequent in IBS-C. Heartburn is more severe/frequent in IBS-C. Upper GI symptoms are common in both diseases. These observations raise interesting questions about pathogenesis/therapy of IBS-C and FC.