FECAL LACTOFERRIN IS A SENSITIVE AND SPECIFIC NON-INVASIVE SURROGATE MARKER FOR THE DIAGNOSIS AND MANAGEMENT OF PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract

Purpose: Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation. Elevated FLA levels have been demonstrated in adult patients with inflammatory bowel disease (IBD). Aims: 1) Determine the ability of FLA to reflect disease activity in pediatric patients with inflammatory and non-inflammatory gastrointestinal disease. 2) Determine the correlation between FLA levels and existing biochemical markers of intestinal inflammation. Methods: Fecal specimens were collected from 148 subjects including 79 with Crohn's disease (CD), 62 with ulcerative colitis (UC), and 7 with Irritable Bowel Syndrome (IBS). FLA was measured by ELISA (IBD-SCAN™ TECHLAB®, Inc) and reported as mcg/ml feces. Disease activity was assessed using Harvey Bradshaw (HBAI) and Pediatric Crohn's Disease Activity Indices (PCDAI). Disease activity was also assessed by Global Physician Assessment (GPA), a derived dichotomous measure that characterizes disease activity based on whether or not a clinician felt a need to alter a subject's medical therapy. Results: Fecal lactoferrin levels were greater in subjects with IBD 1780 ± 326 vs. those with IBS 2.08 ± 0.9 (mean ± SE). The sensitivity and specificity of FLA to distinguish symptomatic subjects with IBD from those with IBS was 95% and 100%, respectively. FLA faithfully discriminated subjects with active IBD, CD, or UC from those with inactive disease (p <0.002) using HBAI, PCDAI, or GPA. Using a Spearman linear regression model, we found highly significant correlations (p <0.0001) between FLA and several commonly used biochemical indices including ESR, hema-tocrit, albumin, and platelet count. ROC analysis demonstrated that FLA outperformed ESR in distinguishing active vs. inactive IBD, UC and CD, but reached statistical significance only in subjects with UC (p = 0.016). FLA levels were significantly higher (1003 ± 547) in 4 subjects that went on to experience a clinical flare in their IBD within two months of specimen collection, relative to 51 subjects that remained in clinical remission (190 ± 90, p = 0.024). Conclusions: Our data confirm FLA as a useful screening tool for detecting IBD in pediatric patients. This non-invasive surrogate marker reflects intestinal disease activity with greater precision than ESR. Elevated levels of FLA may predict patients at greater risk for developing subsequent clinical flares.