• Clinical and Experimental Pediatrics
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• v.57 no.8
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• pp.351-356
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• 2014

Purpose: Among the many factors associated with acute intestinal mucosal infection, numerous studies have proposed the usefulness of fecal calprotectin. The aim of this study was to evaluate the usefulness of fecal calprotectin in the diagnosis of necrotizing enterocolitis (NEC). Methods: We collected 154 stool samples from 16 very low birth weight and premature newborns at the Konyang University Hospital neonatal intensive care unit or neonatal nursery. The stool samples were collected using the Calprest device, and the fecal calprotectin level was measured with the $B\ddot{U}HLMANN$ Calprotectin enzyme-linked immunosorbent assay kit. Results: Fecal calprotectin levels were significantly higher in the NEC group than in the non-NEC group (P=0.02). There was a significant positive linear relationship between the fecal calprotectin level and number of days after birth (P=0.00) in the gestational age <26 weeks group. There was a significant negative linear relationship between the calprotectin level and number of days after birth (P=0.03) in the gestational age ${\geq}26$ weeks and <30 weeks group. There was no difference in the calprotectin levels according to the type and method of feeding between the NEC and non-NEC groups. Conclusion: Fecal calprotectin levels were significantly increased in premature infants with NEC. The fecal calprotectin test is a noninvasive, easy, and useful tool for the diagnosis of NEC.

• BMB Reports
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• v.38 no.4
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• pp.407-413
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• 2005

Calcium and zinc binding protein, calprotectin is a multifunctional protein with broad spectrum antimicrobial and antitumoural activity. It was purified from human neutrophil, using a two-step ion exchange chromatography. Since surface hydrophobicity of calprotectin may be important in membrane anchoring, membrane penetration, subunits oligomerization and some biological roles of protein, in this study attempted to explore the effect of calcium in physiological range on the calprotectin lipophilicity. Incubation of human calprotectin ($50\;{\mu}g/ml$) with different calcium concentrations showed that 1-anilino-8-naphthalene sulfonic acid (ANS) fluorescence intensity of the protein significantly elevates with calcium in a dose dependent manner, suggesting an increase in calprotectin surface hydrophobicity upon calcium binding. Our study also indicates that calcium at higher concentrations (6, 8 and 10 mM) induces aggregation of human calprotectin. Our finding demonstrates that the starting time and the rate constant of calprotectin aggregation depend on the calcium concentration.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1667-1670
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• 2014

Background: Calprotectin in feces seems to be a more sensitive marker for gastrointestinal (GI) cancers than fecal occult blood, but its specificity may be too low for screening average risk populations. This study aims at evaluating the diagnostic value of fecal calprotectin as a screening biomarker for GI malignancies. Materials and Methods: In a case-control study, 100 patients with GI malignancies (50 patients with colorectal cancer and 50 patients with gastric cancer) and 50 controls were recruited in Tabriz Imam Reza and Sina hospitals during a 24-month period. One to two weeks after the last endoscopy/colonoscopy, fecal specimens were collected by the patients and examined by ELISA method for quantitative measurement of calprotectin content. The results were compared between the three groups. Results: The mean fecal calprotectin level was $109.1{\pm}105.3$ (2.3-454.3, median:74), $241.1{\pm}205.2$ (3.4-610.0, median:19.3) and $45.9{\pm}55.1{\mu}g/g$ (1.3-257.1, median:19.3) in gastric cancer, colorectal cancer and control group, respectively, the differences being significant (p<0.001) and remaining after adjustment for age. The optimal cut-off point for fecal calprotectin was ${\geq}75.8{\mu}g/g$ for distinguishing colorectal cancer from normal cases (sensitivity and specificity of 80% and 84%, respectively). This value was ${\geq}41.9{\mu}g/g$ for distinguishing gastric cancer from normal cases (sensitivity and specificity of 62%). Conclusions: Our results revealed that fecal calprotectin might be a useful and non-invasive biomarker for distinguishing colorectal cancer from non-malignant GI conditions. However, due to low sensitivity and specificity, this biomarker may not help physicians distinguishing gastric cancer cases from healthy subjects.

• Clinical and Experimental Pediatrics
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• v.62 no.8
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• pp.287-291
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• 2019

Fecal calprotectin (FC) is a calcium- and zinc-binding protein of the S100 family, mainly expressed by neutrophils and released during inflammation. FC became an increasingly useful tool both for gastroenterologists and for general practitioners for distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome. Increasing evidences support the use of this biomarker for diagnosis, follow-up and evaluation of response to therapy of several pediatric gastrointestinal diseases, ranging from IBD to nonspecific colitis and necrotizing enterocolitis. This article summarizes the current literature on the use of FC in clinical practice.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.1
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• pp.1-12
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• 2022

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as "cystic fibrosis," "intestine," "calprotectin," and "inflammation." Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I²=0), pulmonary function (r=-0.39; 95% CI, -0.58 to -0.15; p=0.002; I²=60%), body mass index (r=-0.514; 95% CI, 0.26 to 0.69; p<0.001; I²=0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; p=0.035; I²=71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.3
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• pp.189-195
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• 2018

Purpose: We investigated fecal calprotectin (FC) levels in preterm infants with and without feeding intolerance (FI), and compared the FC levels according to the type of feeding. Methods: The medical records of 67 premature infants were reviewed retrospectively. The fully enteral-fed infants were classified into two groups; the FI group (29 infants) and the control group (31 infants). Seven infants with necrotizing enterocolitis, sepsis, and perinatal asphyxia were excluded. If breast milk (BM) or preterm formula (PF) could not be tolerated by infants with FI, amino acid-based formula (AAF) was tried temporarily. Once FI improved, AAF was discontinued, and BM or PF was resumed. We investigated the FC levels according to the type of feeding. Results: Significant differences were found in gestational age, birth weight, age when full enteral feeding was achieved, and hospital stay between the FI and control group (p<0.05). The FC levels in the FI group were significantly higher than those in the control group (p<0.05). The FC levels in the AAF-fed infants with FI were significantly lower than those in the BM- or PF-fed infants (p<0.05). The growth velocities (g/d) and z scores were not significantly different between the FI and control group (p>0.05). Conclusion: The FC levels in AAF-fed infants with FI showed significantly lower than those in the BM- or PF-fed infants with FI. The mitigation of gut inflammation through the decrease of FC levels in AAF-fed infants with FI could be presumed.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.4
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• pp.230-237
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• 2015

Purpose: Various gastrointestinal factors may contribute to maladaptive behavior in children with autism spectrum disorders (ASD). To determine the association between maladaptive behavior in children with ASD and gastrointestinal symptoms such as severity, intestinal microbiota, inflammation, enterocyte damage, permeability and absorption of opioid peptides. Methods: This observational cross-sectional study compared children with ASD to healthy controls, aged 2-10 years. Maladaptive behavior was classified using the Approach Withdrawal Problems Composite subtest of the Pervasive Developmental Disorder Behavior Inventory. Dependent variables were gastrointestinal symptom severity index, fecal calprotectin, urinary D-lactate, urinary lactulose/mannitol excretion, urinary intestinal fatty acids binding protein (I-FABP) and urinary opioid peptide excretion. Results: We did not find a significant difference between children with ASD with severe or mild maladaptive behavior and control subjects for gastrointestinal symptoms, fecal calprotectin, urinary D-lactate, and lactulose/mannitol ratio. Urinary opioid peptide excretion was absent in all children. Children with ASD with severe maladaptive behavior showed significantly higher urinary I-FABP levels compared to those with mild maladaptive behavior (p=0.019) and controls (p=0.015). Conclusion: In our series, maladaptive behavior in ASD children was not associated with gastrointestinal symptoms, intestinal inflammation (no difference in calprotectin), microbiota (no difference in urinary D-lactate) and intestinal permeability (no difference in lactulose/manitol ratio). ASD children with severe maladaptive behavior have significantly more enterocyte damage (increased urinary I-FABP) than ASD children with mild maladaptive behavior and normal children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.1
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• pp.43-49
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• 2023

Purpose: The cow's milk-related-symptom-score (CoMiSS) tool was developed as an awareness tool for the assessment of cow's milk-related symptoms in infants or children. Fecal calprotectin (FC) is a noninvasive biomarker of gut inflammation that can be measured in serum and stool. This study aimed to investigate the relationship between FC levels and CoMiSS scores in infants with cow's milk protein allergy. Methods: Infants (aged 6-12 months) who were allergic to cow's milk protein were enrolled prospectively. Following completion of the CoMiSS scoring, the infants were divided into group 1 (positive CoMiSS scores ≥12) and group 2 (negative CoMiSS scores <12). FC was measured using immunoassay. Results: Of the 120 infants enrolled in this study, 60 (50.0%) had positive CoMiSS scores (group 1), while 60 (50.0%) had negative scores (group 2). The mean FC level was higher in the infants in group 1 than those in group 2 (2,934.57 ㎍/g vs. 955.13 ㎍/g; p<0.001). In addition, there was a positive correlation between FC and CoMiSS scores (R=0.168, p<0.0001). A FC level of 1,700 ㎍/g provided a sensitivity of 98.3%, specificity of 93.3%, and accuracy of 95.8% for the diagnosis of cow's milk protein allergy (CMPA). Conclusion: FC measurement may have a role in the assessing infants with CMPA.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.181-187
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• 2020

Fecal calprotectin (FC) is a marker used for the differential diagnosis of inflammatory bowel disease (IBD). FC is also used to determine the effects of treatment and recurrence prediction because of its non-decomposition by bacteria, relative week stability at room temperature, and its uniform distribution within feces. Healthy male and female adults between the age of 30 and 80 living in Jeju were selected for this study. The FC concentration in the healthy control group (N=45) was distributed widely as 0~545.9 ㎍/g and showed a significant difference with age in healthy adults. The FC concentration in adults over 70 years old (80.6 years on average) was 160.3 ㎍/g. The result is approximately 10 times higher than in adults below 50 years (44 years on average), with FC concentrations at 15.88 ㎍/g. Moreover, adults over 50 years, with an average age of 59.6, had FC concentrations of 35.46 ㎍/g, which were two times higher than the below 50-year-old group, confirming the significant correlation between age and FC concentration. As the FC test is a non-invasive and cost-effective objective marker in IBD tests, a suitable cut-off value is required for different ages. This study provides the baseline data for differential diagnoses.

• Clinical and Experimental Pediatrics
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• v.62 no.10
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• pp.400-404
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• 2019

Background: An increase in the numbers of patients with gastrointestinal symptoms has recently been observed. Purpose: To investigate the effects of proton pump inhibitor (PPI) therapy on intestinal inflammation in children and adolescents as confirmed by clinical manifestations and objectively assessed by fecal calprotectin (FC) level measurement. Methods: Consecutive children (aged 3-18 years) who presented with gastrointestinal symptoms and were treated with or without PPI for at least 1 month were enrolled. Patients were divided into PPI and non-PPI groups. The PPI group was further subdivided by treatment duration and type of PPI used. Stool samples were collected for FC evaluation at baseline and after treatment and clinical data and FC levels were compared between the groups. Results: Fifty-one patients (15 boys, 36 girls) were enrolled in the study. The PPI group included 37 patients, while the non-PPI group included 14 patients. Clinical symptoms were not significantly different. FC levels and laboratory results, including C-reactive protein levels, white blood cell count, and absolute neutrophil count, were not statistically different before versus after PPI treatment. After treatment, FC levels decreased to 8.1 mg/kg (-575.4 to 340.3 mg/kg) in the PPI group and increased to 5.6 mg/kg (-460.0 to 186.9 mg/kg) in the non-PPI group compared to those before treatment (P=0.841). The number of patients with increased FC levels was not significantly different between the 2 groups (48.6% vs. 64.3%, P=0.363), similar to that observed in patients with an FC level > 50 mg/kg (24.3% and 7.1%, P=0.250). PPI therapy type and duration did not affect the FC levels (P=0.811 and P=0.502, respectively). Conclusion: Although we aimed to confirm the evidence of intestinal inflammation due to PPI use in children and adolescents through clinical symptoms and FC measurement, no significant changes were observed.