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Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort.

ABSTRACT: We sought to assess the evolution of Crohn's disease behavior in an American population-based cohort.Medical records of all Olmsted County, Minnesota residents who were diagnosed with Crohn's disease from 1970 to 2004 were evaluated for their initial clinical phenotype, based on the Montreal Classification. The cumulative probabilities of developing structuring and/or penetrating complications were estimated using the Kaplan-Meier method. Proportional hazards regression was used to assess associations between baseline risk factors and changes in behavior.Among 306 patients, 56.2% were diagnosed between the ages of 17 and 40 years. Disease extent was ileal in 45.1%, colonic in 32.0%, and ileocolonic in 18.6%. At baseline, 81.4% had nonstricturing nonpenetrating disease, 4.6% had stricturing disease, and 14.0% had penetrating disease. The cumulative risk of developing either complication was 18.6% at 90 days, 22.0% at 1 year, 33.7% at 5 years, and 50.8% at 20 years after diagnosis. Among 249 patients with nonstricturing, nonpenetrating disease at baseline, 66 changed their behavior after the first 90 days from diagnosis. Relative to colonic extent, ileal, ileocolonic, and upper GI extent were significantly associated with changes in behavior, whereas the association with perianal disease was barely significant.In a population-based cohort study, 18.6% of patients with Crohn's disease experienced penetrating or stricturing complications within 90 days after diagnosis; 50% experienced intestinal complications 20 years after diagnosis. Factors associated with development of complications were the presence of ileal involvement and perianal disease.

SUBMITTER: Thia KT

PROVIDER: S-EPMC2950117 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort.

Thia Kelvin T KT Sandborn William J WJ Harmsen William S WS Zinsmeister Alan R AR Loftus Edward V EV

Gastroenterology 20100714 4

<h4>Background and aims</h4>We sought to assess the evolution of Crohn's disease behavior in an American population-based cohort.<h4>Methods</h4>Medical records of all Olmsted County, Minnesota residents who were diagnosed with Crohn's disease from 1970 to 2004 were evaluated for their initial clinical phenotype, based on the Montreal Classification. The cumulative probabilities of developing structuring and/or penetrating complications were estimated using the Kaplan-Meier method. Proportional ...[more]

PMID: 20637205

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Project description:Crohn's Disease (CD) is a relapsing inflammation of the gastrointestinal tract that affects a young working age population and is increasing in developing countries. Half of all sufferers will experience stricturing or fistulizing intestinal complications that require extensive surgical interventions and neither genes nor clinical risk factors can predict this debilitating natural history. We applied discovery and verification phase studies as part of an NCI-FDA modeled biomarker pipeline to identify differences in the low-mass (<25kDa) blood-serum proteome between CD behavioral phenotypes. A significant enrichment of epithelial component proteins was identified in CD patients with intestinal complications using quantitative proteomic profiling with label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). DAVID 6.7 (NIH) was used for functional annotation analysis of detected proteins and immunoblotting and multiple reaction monitoring (MRM) to verify a priori findings in a secondary independent cohort of complicated CD (CCD), uncomplicated inflammatory CD (ICD), Th1/17 pathway inflammation controls (rheumatoid arthritis), inflammatory bowel disease controls (ulcerative colitis), and healthy controls. Seventy-six high-confidence serum proteins were modulated in CCD versus ICD by LC-MS/MS (p < 0.05, FDR q<0.01), annotating to pathways of epithelial barrier homeostasis (p < 0.01). In verification phase, a putative serology panel developed from discovery proteomics data consisting of desmoglein-1, desmoplakin, and fatty acid-binding protein 5 (FABP5) distinguished CCD from all other groups (p = 0.041) and discriminated complication in CD (70% sensitivity and 72.5% specificity at score ≥1.907, AUC = 0.777, p = 0.007). An MRM assay secondarily confirmed increased FABP5 levels in CCD (p < 0.001). In a longitudinal subanalysis-cohort, FABP5 levels were stable over a two-month period with no behavioral changes (p = 0.099). These studies along the biomarker development pipeline provide substantial proof-of-principle that a blood test can be developed specific to transmural intestinal injury. Data are available via the PRIDE proteomics data repository under identifier PXD001821 and PeptideAtlas with identifier PASS00661.

Dataset Information

Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort.

Publications

Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort.

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