Surrogate Marker Of Intestinal Inflammation Research Articles

Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease.

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn’s disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.

Occult Blood in Feces Is Associated with Increased Risk of Psoriasis

Background: The fecal immunochemistry test (FIT) has been proposed as a surrogate marker of intestinal inflammation. Psoriasis is a chronic inflammatory skin disease that is linked to underlying systemic inflammatory conditions, including inflammatory bowel disease. Methods: We investigated the association between occult blood in feces and the risk of psoriasis using data from the National Health Insurance System. This study was conducted involving 1,395,147 individuals who underwent health examinations from January 2009 to December 2012 and were followed up until the end of 2017. Results: The incidence of psoriasis (per 1,000 person-years) was 3.76 versus 4.14 (FIT-negative versus FIT-positive group) during a median follow-up of 6.68 years. In the multivariable-adjusted model, the hazard ratios for psoriasis were 1.03 for one positive FIT result, 1.12 for two positive FIT results, and 1.34 for three positive FIT results compared with negative FIT results. Conclusion: The risk of psoriasis was significantly increased in patients with positive FIT results compared to the FIT-negative population.

Surrogate Markers of Intestinal Inflammation in Paediatric Patients with Inflammatory Bowel Disease.

Endoscopic evaluation is the gold standard for monitoring the disease activity in inflammatory bowel disease (IBD) but the procedure is invasive and not appropriate for frequent use, especially in the paediatric population. The aim of the present study was to assess the correlation between the levels of several inflammatory biomarkers and the degree of intestinal inflammation in paediatric patients with IBD. A single center study including 31 children with ulcerative colitis (UC) and 22 children with Crohn's disease (CD) with different disease duration and activity. All participants provided blood samples to measure the levels of white blood cell count, platelets, C-reactive protein, erythrocyte sedimentation rate, albumin and fibrinogen, and faecal samples for measurement of faecal calprotectin and faecal alpha-1 antitrypsin. All participants underwent endoscopic evaluation. Endoscopic disease activity was assessed according to the Mayo Endoscopic Subscore and Simple Endoscopic Score for Crohn's Disease in UC and CD patients, respectively. 135 visits were included: 73 for UC patients and 62 for CD patients. In UC patients the strongest correlation was between the Mayo Endoscopic Subscore and the faecal calprotectin (r=0.867, p<0.001) followed by the albumin (r=0.523, p<0.001) and the C-reactive protein (r=0.487, p<0.001). In CD the strongest correlation was between the Simple Endoscopic Score for Crohn's disease and the faecal calprotectin (r=0.872, p<0.001) followed by the C-reactive protein (0.708, p<0.001) and the erythrocyte sedimentation rate (0.605, p<0.001). The faecal calprotectin is a valuable surrogate marker of intestinal inflammation that is useful for monitoring of a disease activity in paediatric patients with IBD.

Validation of a new extraction device for measuring faecal calprotectin in inflammatory bowel disease, and comparison to established extraction methods

Objective: Faecal (f-) calprotectin is a widely used surrogate marker of intestinal inflammation. F-calprotectin analysis is labour demanding partly due to a time consuming extraction step. The aim of this project was to validate a new extraction method for f-calprotectin. Material and methods: A prospective multicentre study included 135 patients with an established diagnosis of inflammatory bowel disease. The patients submitted a faeces sample, which was extracted with both the conventional method at the participating laboratory and the new extraction device. The extracts were analyzed by an automated ELISA instrument. Results: Method comparison of the traditional method and the new device showed a slope of 1.01 (0.93–1.07) with intercept of − 2.2 (− 4.9–0.6). The Spearman rank correlation coefficient was 0.96. Conclusions: The new extraction device is a reliable and time saving alternative to the conventional extraction method.

Faecal calprotectin: Management in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder which leads to an inflammation of the gastrointestinal tract. A tailored therapy to achieve mucosal healing with the less adverse events has become a key issue in the management of IBD. In the past, the clinical remission was the most important factor to consider for adapting diagnostic procedures and therapeutic strategies. However, there is no a good correlation between symptoms and intestinal lesions, so currently the goals of treatment are to achieve not only the control of symptoms, but deep remission, which is related with a favourable prognosis. Thus, the determination of biological markers or biomarkers of intestinal inflammation play a crucial role. Many biomarkers have been extensively evaluated in IBD showing significant correlation with endoscopic lesions, risk of recurrence and response to treatment. One of the most important markers is faecal calprotectin (FC). Despite calprotectin limitations, this biomarker represents a reliable and noninvasive alternative to reduce the need for endoscopic procedures. FC has demonstrated its performance for regular monitoring of IBD patients, not only to the diagnosis for discriminating IBD from non-IBD diagnosis, but for assessing disease activity, relapse prediction and response to therapy. Although, FC provides better results than other biomarkers such as C-reactive protein and erythrocyte sedimentation rate, these surrogate markers of intestinal inflammation should not be used isolation but in combination with other clinical, endoscopic, radiological or/and histological parameters enabling a comprehensive assessment of IBD patients.

Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16-50 years.

Background:Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer.Aim:This large retrospective study aimed to determine the most effective use of FC in patients aged 16–50 presenting with GI symptoms.Methods:FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses.Results:895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 μg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of ≥ 50 μg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00.Conclusions:Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians.

Detection of Calprotectin and Apoptotic Activity in the Colon of Marmosets with Chronic Diarrhea

ABSTRACT The common marmoset (Callithrix jacchus) is used as a non-human primate laboratory animal. Marmoset wasting syndrome (MWS) is a disease endemic to captive colonies, and the pathogenesis is unclear. In the present study, marmosets with chronic bloody high-viscosity diarrhea, which is a contributing factor to MWS, were evaluated, and inflammation in the colon was found. Calprotectin is a surrogate marker of intestinal inflammation and induces apoptosis. Marmosets with chronic diarrhea exhibited higher levels of fecal calprotectin. Histochemical analyses showed high expression of calprotectin in the extravascular neutrophils and apoptosis in the chronic colitis lesions. No internal microbiological diseases were identified. Although the cause of chronic colitis was not identified, the marmoset could be a useful model of inflammatory bowel disease.

Biomarkers in management of inflammatory bowel disease.

In recent years the use of faecal and serologic biomarkers has been evaluated in the diagnosis and management of inflammatory bowel disease (IBD). Faecal calprotectin (FC) has been proposed as a surrogate marker for intestinal inflammation; elevated concentrations in IBD patients have been confirmed in numerous studies. Already available rapid calprotectin tests help to differentiate between IBD and irritable bowel syndrome. Faecal calprotectin greatly correlates with endoscopic activity scales and reflects the mucosal healing; thus in patients in clinical remission high levels of it correlate with increased risk of disease relapse in the following 12 months. Adapting the calprotectin assay as a screening test before colonoscopy enables a significant reduction in endoscopic procedures. ANCA/ASCA antibodies have been used in IBD diagnosis and to distinguish CD from ulcerative colitis (UC). Lactoferrin and S100A12 protein were also used to assess the disease activity. This review aims to present the actual potential of biomarker assays for faster diagnosis of IBD and their ability to monitor the disease course, predict exacerbations and improve the way IBD is managed.

Effect of Bowel Cleansing for Colonoscopy on Fecal Calprotectin Levels in Pediatric Patients

The recent development of easily applicable fecal surrogate markers of intestinal inflammation, such as fecal calprotectin (FC), has provided a new means for objectively assessing disease activity in patients with chronic inflammatory bowel disease. Because the use of these markers is about to emerge, it is important to be aware of the possible limitations of measurements. We assessed levels of FC during bowel cleansing. In patients with high FC levels at baseline, the values measured during bowel cleansing varied considerably, remaining high or even returning to normal. Thus, stool sampling for FC assessment is not recommended during bowel preparation for colonoscopy.

Tu1235 Multicentre Follow-up Study of Phagocyte-Derived S100A12 as a Surrogate Marker of Intestinal Inflammation in Inflammatory Bowel Disease

demonstration of MSc markers in granulomas of ITB and evaluate whether the distribution of MSc markers could differentiate between granulomas of CD & ITB. Materials & methods: We retrospectively enrolled 17 patients with confirmed ITB(8)or CD(9) and granulomas on histopathology. The 8 ITB cases were culture +ve for myco.tb and mTB PCR +ve. The 9 CD cases were identified according to WHO criteria for definite CD. Paraffinembedded tissue blocks were sectioned to determineMScmarkers CD29, CD90 and CD73 expression by immunofluorescence (Bioimager , BD BioSciences,USA). Conjugated monoclonal antibodies against CD29 (mouse, 313001; BIolegend,USA.), CD73 (mouse, ab54217) & CD90 (rabbit, ab92574) (Abcam) were used for identification of the MScs. Double staining was carried to confirm presence of MScs. Results: CD29 and CD90 positive cells were noted around both ITB and CD granulomas. However CD73, a marker for permeability barrier was expressed around the granulomas of ITB alone and was completely absent in the granulomas of CD (Fig 1). Double staining showed that CD73 Cells were also expressing CD90 & CD29 confirming MSc. Discussion: The differential CD73 expression around ITB granuloma indicates that Mtb evades host immunity by recruiting MScs with high CD73. The study also demonstrates CD73 expression in MScs as a marker for differentiation between granulomas of ITB and CD. These features postulate and support the loss of permeability barrier (reduced CD73 expression) in CD but present in ITB due to presence of the bacterium. MSC therapy has shown benefit in CD2. Conclusion: Granulomas of ITB and CD can be differentiated by CD73 MSc surface marker expression.MSCs with increased CD73 expression could be the future for therapeutic intervention in Crohns. Ref: 1. Raghuvanshi S et al Proc Natl Acad Sci USA. 2010Dec 14; 107(50):21653-8 2. Ciccocioppo R et al Gut 2011; 60:788-98

Faecal calprotectin - a useful tool in the management of inflammatory bowel disease

Inflammatory bowel disease (IBD) should be suspected in any patient presenting with chronic or recurrent abdominal pain and diarrhoea. Current guidelines suggest performing invasive endoscopy with histological sampling for further diagnosis. Measuring calprotectin, a neutrophilic protein, in faeces has been proposed as a surrogate marker of intestinal inflammation. Calprotectin values have been shown to reliably differentiate between IBD and non-organic disease in symptomatic patients and, when elevated, warrant early endoscopic investigation to rule out IBD and other organic pathologies. Endoscopy with histological sampling is also used to evaluate disease activity and here, too, faecal calprotectin values seem to correlate well. In a number of studies, faecal calprotectin values have consistently shown to better assess mucosal inflammation than clinical indices and serum markers. Calprotectin's advantage of non-invasive monitoring of disease activity is especially beneficial when considering the dynamics of repeated measurements. Mucosal healing (MH) has been associated with sustained clinical remission, reduced rates of hospitalisation and of surgical resection, both in Crohn's disease and ulcerative colitis patients. Elevated faecal calprotectin levels in patients in clinical remission are associated with increased risk of disease relapse within 12 months follow-up. In most clinically quiescent IBD, residual mucosal inflammation is still present; it appears that faecal calprotectin can detect subclinical mucosal inflammation and thus might identify patients at risk for relapse. In summary, measuring faecal calprotectin can be highly useful in the diagnosis and disease management of patients with IBD and could help predict disease course.

Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome

Background and aimsThe neutrophil protein calprotectin has been investigated as a surrogate marker for intestinal inflammation. This study was designed to contrast fecal calprotectin levels in patients with inflammatory and non-inflammatory intestinal diseases and to compare the results obtained from the standard ELISA-based method with those obtained from a novel desk-top device. MethodsSoluble proteins were extracted from stool samples of 50 participating patients, including those diagnosed with Ulcerative Colitis, Crohn's Disease or IBS, and volunteers with no known intestinal problems. Calprotectin was assessed in the extracted material using the “desk top” Bühlmann Quantum Blue Reader® or by standard ELISA techniques. ResultsThe mean concentration of calprotectin in the IBD patients group was significantly higher than the mean concentration found in IBS patients and healthy controls (p=0.01). Calprotectin concentrations in IBS patients and controls were indistinguishable. IBD patients that had undergone recent surgery displayed scores similar to controls and IBS patients. Excluding these patients yielded a specificity of 100% for results from both CD and UC patients and an accuracy rate of 1 for CD and 0.89 for UC patients in ROC analysis. Quantum Blue Reader® calprotectin levels were available within 30min and correlated well with results derived from standard ELISA assays, which took over 8h to complete. ConclusionOur results confirm the effective use of fecal calprotectin levels in differentiating non-inflammatory from active inflammatory intestinal diseases. The desk top Bühlmann Quantum Blue Reader® exhibits a fast, non-invasive, and reliable way of identifying an inflammatory intestinal disease.

Plasma citrulline as surrogate marker of intestinal inflammation in pediatric and adolescent with Crohn’s disease: preliminary report

Several researchers have found that plasma citrulline could be a marker of reduced enterocyte mass. The aim of this study was to assess the relationship between plasma citrulline and bowel inflammation and/or disease location in pediatric and adolescent Crohn's disease (CD) patients. Between January 2008 and January 2010, 31 CD patients and 44 controls were included in our study, and 15 out of the 31 CD patients continued a prospective survey. We evaluated the differences between groups, at baseline, in plasma citrulline and glutamine and between their baseline and final values during the prospective survey, and correlation between baseline values of citrulline and duration of disease, C-reactive protein, and fecal calprotectin. Mean citrulline value was 33.0 ± 7.5μmol/L in controls and 23.5 ± 8.4μmol/L in CD patients (P < 0.0001). Plasma citrulline was significantly lower in patients with small bowel (SB) location than in patient with only ileo-colon disease (14.2 ± 5.5 and 24.7 ± 8.0, respectively; P = 0.0037). Citrulline ≤22μmol/L reached sensitivity of 100% (95% confidence interval (CI) 54-100) and specificity of 98% (CI 89-99) in differentiating control subjects from CD with SB location. CD patients have reduced concentration of plasma citrulline than controls. Intestinal damage rather than inflammation seems to be responsible for the reduced biosynthesis of citrulline, which decreases particularly in CD patients with SB location. This finding suggests the potential role of citrulline as marker of disease location, but future works will be needed to confirm this suggestion.

Faecal calprotectin in the diagnosis of inflammatory bowel disease

Suspicion of inflammatory bowel disease should be raised in any patient with chronic or recurrent abdominal pain and diarrhoea. However, symptoms of inflammatory bowel disease (IBD) overlap with functional gastrointestinal disorders and those patients may not need endoscopy. Currently, colonoscopy with multiple biopsies is considered the gold standard to establish the diagnosis of IBD. Unfortunately, patient selection for endoscopy based on symptoms is not reliable. The use of guidelines of appropriateness for endoscopy yields significantly more significant findings but the selection criteria suffer from low specificity. Calprotectin is a calcium binding protein of neutrophil granulocytes that correlates well with neutrophil infiltration of the intestinal mucosa when measured in faeces. In the last decade, a large body of evidence on the diagnostic value of faecal calprotectin has accumulated and measurement of calprotectin in faeces has been suggested as a surrogate marker of intestinal inflammation. Testing of faecal calprotectin has been highly useful to distinguish organic from functional intestinal disorders in patients with abdominal complaints. Additionally, faecal calprotectin has reliably identified colonic inflammation in patients with suspected IBD. The use of this inexpensive and widely available test in the evaluation and risk stratification in patients with abdominal complaints is likely to increase in the future.

Value of mucosal assessment and biomarkers in inflammatory bowel disease

Clinical remission at a single point in time provides surprisingly little predictive value for future inflammatory bowel disease (IBD) activity owing to the waxing and waning nature of the disease course. Furthermore, patients often present with complications of IBD despite apparent clinical remission, suggesting that undetected subclinical inflammation is driving these complications. This has led to research on a variety of surrogate markers of biologically significant asymptomatic inflammatory disease activity, including endoscopic healing, histologic normalization and biomarkers of inflammation in the blood and stool. If these have strong predictive value, they could be used to risk-stratify patients and justify the early use of immunomodulators and anti-TNF agents. Mucosal healing has been associated with positive outcomes in IBD, but the supporting data are largely retrospective and subject to channeling bias, and it is not clear whether complete mucosal healing produces better outcomes than partial healing. Stool and blood biomarkers correlate well with mucosal inflammation, but are imperfect surrogates for mucosal healing. Before using surrogate markers of intestinal inflammation to justify long-term, potentially toxic and costly therapy, prospective longitudinal studies are needed to identify surrogate end points with cut points that justify changes in therapy, and which therapies provide cost-effective benefits for mild, moderate or severe inflammation.

Faecal calprotectin in children with clinically quiescent inflammatory bowel disease

Objective. The use of faecal calprotectin as a surrogate marker for intestinal inflammation is emerging. However, the data on faecal calprotectin during maintenance therapy in children with inflammatory bowel disease, IBD, are sparse. Our aim was to study faecal calprotectin levels in paediatric IBD during clinically quiescent disease and to investigate if high levels were associated with a flare-up of the disease. Subjects and methods. Faecal calprotectin level was measured in 72 children with paediatric IBD in clinical remission (median age 13 years). Of these, 37 children had been in clinical remission for more than a year, 20 for 6–12 months and 15 for 3 to <6 months. The clinical outcome of the patients was followed up to the first relapse or up to 12 months. Results. When in clinical remission, 35% (25/72) of the children had normal faecal calprotectin (<100 μg/g) and 13% (9/72) a very high level (>1000 μg/g) while not reporting symptoms. A clinical relapse occurred in 35% (25/72) during the subsequent 12 months. When in clinical remission, the predictive value of faecal calprotectin for an overt relapse was low ranging from 0.396 to 0.429 for faecal calprotectin values >100 μg/g or >1000 μg/g, respectively. The negative predictive value was 0.75 for values <100 μg/g. Conclusions. In paediatric IBD, subjective symptoms and clinical assessment associate poorly with the levels of faecal calprotectin. During maintenance medication in colonic disease, the probability of staying in clinical remission for a subsequent year is high if faecal calprotectin value is low.

Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease

Faecal calprotectin has been proposed as a non-invasive surrogate marker of intestinal inflammation in inflammatory bowel disease. Close correlation between faecal calprotectin concentration and faecal leukocyte excretion quantified with (111)indium has been described. This faecal marker can be detected using simple and cheap techniques. Faecal calprotectin has a good diagnostic precision for separating organic and functional intestinal diseases. However, the specificity for the diagnosis of inflammatory bowel disease is lower than desirable, as several diseases other than inflammatory bowel disease -- specially colorectal neoplasia and gastrointestinal infection -- can also increase faecal calprotectin. High concentration of calprotectin in faeces is a strong argument to carry out a colonoscopy in order to rule out the presence of inflammatory bowel disease or other organic pathologies. Parallelism between faecal calprotectin levels and inflammatory bowel disease activity has been confirmed, although this faecal marker appears to better reflect the disease activity in ulcerative colitis than in Crohn's disease. Faecal calprotectin's capacity to predict inflammatory bowel diseases relapse is promising. It has been suggested that, in inflammatory bowel disease patients receiving treatment, a normalization or decrease in faecal calprotectin concentrations is an accurate indicator of endoscopic healing. Greater faecal calprotectin concentration has been shown in asymptomatic first-degree relatives of patients with inflammatory bowel disease, suggesting that there is a high prevalence of subclinical intestinal inflammation in them.

Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases

Inflammatory bowel diseases (IBD) are characterized by periods of remission with recurrent episodes of symptom exacerbation because of acute intestinal inflammation, which is correctly evaluated by endoscopy with biopsy sampling. However, many surrogate markers of intestinal inflammation, including fecal calprotectin (FC), are detected as potential predictors of mucosal inflammation in IBD patients. The aim of our study was to retrospectively assess the clinical efficacy of the calprotectin assay in determining histological relapses of pediatric IBD patients. We retrospectively reviewed the histological examinations, clinical records, and FC values of patients who had undergone colonoscopy at our hospital over an 8-year period, from December 31, 1998, to December 31, 2006. Only patients with a first histological examination showing a quiescent IBD who submitted to a second histological examination during the next 3 years were selected. Seventy-three IBD patients, all with a first biopsy showing a quiescent IBD, were studied; at the second histological examination, 32 presented with relapse and 41 presented with remission. Relapsed patients showed significantly increased FC levels compared with nonrelapsed patients. A FC value of 275 mug/g achieved sensitivity and negative predictive value of 97% and specificity and positive predictive value of 85% in predicting histological relapse. FC seems to be a direct measure of intestinal inflammation and therefore a good marker of the risk of histological relapse in pediatric IBD patients. The application of this test in clinical practice may enable the avoidance of invasive tests as well as targeting treatment.

Fecal Lactoferrin Is a Sensitive and Specific Marker of Disease Activity in Children and Young Adults With Inflammatory Bowel Disease

Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation that is elevated in patients with inflammatory bowel disease. However, the correlation between FLA levels and serological markers of disease activity has not been previously reported, to our knowledge. In the present study we evaluated the ability of FLA levels to reflect disease activity in pediatric patients with inflammatory bowel disease. We further assessed the relationship between FLA levels and customary laboratory and clinical measures of inflammation. Fecal specimens were collected from 148 consecutive pediatric patients (79 with Crohn disease, 62 with ulcerative colitis, and 7 with irritable bowel syndrome) and 22 healthy control individuals. Lactoferrin was measured by enzyme-linked immunosorbent assay (IBD-SCAN, TECHLAB, Inc). Disease activity was assessed at the time of sample provision by laboratory measures (including erythrocyte sedimentation rate [ESR] and albumin) and previously validated disease activity indices (Pediatric Crohn Disease Activity Index, Kozarek, Harvey Bradshaw Activity Index). Lactoferrin levels were significantly higher in patients with ulcerative colitis (1880 +/- 565 microg/mL) (mean +/- SE) or Crohn disease (1701 +/- 382 microg/mL) than in healthy control individuals under 21 years of age (1.17 +/- 0.47 microg/mL, P < 0.001). Lactoferrin levels correlated significantly with ESR, hematocrit, albumin, and platelet count (P < 0.001). Receiver operating characteristic curve analysis revealed that FLA levels were comparable to ESR in detecting patients with clinically active disease (P < 0.001). Patients who experienced a clinical flare within 2 months of specimen collection displayed higher lactoferrin levels (845 +/- 452 microg/mL) than did those who remained in clinical remission (190 +/- 90 microg/mL, P = 0.003). Data presented here demonstrate that FLA is a sensitive and specific biochemical marker of inflammation for use in the diagnosis and interval assessment of pediatric patients with IBD, and its level correlates well with both clinical disease activity indices and ESR. Elevated levels of FLA may also identify patients at greater risk for the development of subsequent clinical flares.

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

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.