Calprotectin as a marker of bowel inflammation

Fecal Calprotectin ◽

Bacterial Degradation ◽

Human Neutrophils ◽

Non Invasive

In the last years the need for a non-invasive diagnostic tool that would help to discriminate between organic and functional gastrointestinal disorders directed research towards potential immunological markers. A great number of non-invasive bio-markers has been proposed, including eosinophilic cationic protein, elastase, esterase, myeloperoxidase, lysozyme, lactoferrin, and calprotectin. Compared to other biomarkers, calprotectin (also called MRP8/14, calgranulin A/B , S100 A8/A9) may offer advantages based on its biological characteristics. Calprotectin is a 36.5-kDa, calcium and zinc binding polypeptide which constitutes about 60% of soluble cytosol proteins in human neutrophils. It is also found in monocytes, keratinocytes, muscle tissue and infiltrating tissue macrophages. When bound to calcium it becomes resistant to proteolysis and colonic bacterial degradation. This make is stable for up to 1 week at room temperature and facilitate its determination in feces. Calprotectin is involved in the regulation of the inflammatory process, participate to the early innate immune response and exert antimicrobial, anti-proliferative and apoptotic properties. Fecal calprotectin is a direct measure of mucosal inflammation activity and becomes detectable when intestinal inflammation is still at an insufficient level to cause an increase in serum inflammation markers. In the last decade fecal calprotectin has been proposed as a marker to rule out acute and chronic intestinal inflammatory diseases in children with typical gastrointestinal symptoms. Many studies demonstrated its diagnostic utility in identifying children and adults with inflammatory bowel disease and correlate with the degree of disease activity. The detection of elevated levels of fecal calprotectin in healthy infants during the first few weeks of age, limits their use as screening test for intestinal inflammatory diseases in early life. Despite this evidence, the measurement of calprotectin in the serum has been proposed to identify neonates with necrotizing enterocolitis. Recent studies have shown higher fecal calprotectin levels in infants with irritable bowel syndrome and colics, compared with healthy controls. Additionally, a correlation was found between fecal calprotectin concentration and IBS clinical presentation severity. However, these studies do not provide data on diagnostic accuracy in distinguish between organic and functional gastrointestinal disorders. Despite significant limitations, these evidences suggest the presence of a subtle inflammatory process underlying functional gastrointestinal disorders and open new perspectives on their pathogenesis. Fecal calprotectin may play a role that could be revealed in further, specifically designed, studies. Changes in microflora, permeability, calprotectin excretion and other inflammatory biomarkers, should be investigated to clarify if a continuum exists between inflammatory conditions and intestinal functional diseases.

Calprotectin as a marker of bowel inflammation

10.7287/peerj.preprints.65v1 ◽

2013 ◽

Author(s):

Gianluca Terrin ◽

Andrea Pietravalle

Keyword(s):

Inflammatory Process ◽

Intestinal Inflammation ◽

Inflammatory Diseases ◽

Fecal Calprotectin ◽

Bacterial Degradation ◽

Human Neutrophils ◽

Non Invasive

Prevalence of functional gastrointestinal disorders in infants and young children in China

BMC Pediatrics ◽

10.1186/s12887-021-02610-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Huang ◽

Serene Yaling Tan ◽

Panam Parikh ◽

Vanitha Buthmanaban ◽

Shaman Rajindrajith ◽

...

Keyword(s):

Young Children ◽

Maternal Education ◽

Functional Constipation ◽

Cross Sectional ◽

Validated Questionnaire ◽

Rome Iv ◽

Infants And Young Children

Abstract Background The prevalence of functional gastrointestinal disorders (FGIDs) in children, particularly from Asia, is largely unknown. There are not many studies done in Asia especially using the Rome IV criteria. The aim of this study is to assess the prevalence of FGIDs in infants and young children in a representative sample in China. Methods A prospective, cross-sectional, community-based survey was conducted among healthy infants and young children between the ages of 0–4 years in Jinhua and Shanghai, China. A total of 2604 subjects (1300 subjects from Jinhua and 1304 subjects from Shanghai) completed a validated questionnaire on pediatric gastrointestinal symptoms. FGIDs in infants and young children were diagnosed using the Rome IV criteria. Results According to the Rome IV criteria, the prevalence of having a FGID in Chinese infants and young children is 27.3%. Infant regurgitation (33.9%) was the most common FGID among the 0–6 months old while functional constipation (7.0%) was the most common among the 1–4 years old. Risk factor analysis revealed that prevalence of infantile colic was higher with better maternal education and low birth weight. Prevalence of infantile regurgitation was significantly greater in males, living in a rural area, being exclusively breast fed at least up to 4 months and starting formula feeds within the first month. The risk of functional constipation was lower for infants who were delivered vaginally. Conclusions Infantile regurgitation was the most common FGID in Chinese infants while functional constipation was most prevalent among young Chinese children. Trial registration Netherlands Trial Registry Identifier: NL6973/NTR7161.

Evaluation of Human Fecal Calprotectin Detection Kits and Their Potential use as Non-Invasive Intestinal Biomarker of Infectious Enterocolitis in Pigs

10.21203/rs.3.rs-267458/v1 ◽

2021 ◽

Author(s):

Jéssica Barbosa ◽

Lucas Rodrigues ◽

Daniel Columbus ◽

Juan Aguirre ◽

John Harding ◽

...

Keyword(s):

Intestinal Inflammation ◽

Point Of Care ◽

Sandwich Elisa ◽

Fecal Calprotectin ◽

Field Application ◽

Dipstick Test ◽

Infectious Colitis ◽

Fecal Samples ◽

Non Invasive ◽

Infectious Enterocolitis

Abstract Background: Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. Results: Fecal samples from pigs with colitis (n=18) were collected from animals experimentally inoculated with B. hyodysenteriae G44 or from sham-inoculated controls. Fecal samples from pigs with enteritis (n=14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium or from sham-inoculated controls. For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method.Conclusions: Fecal calprotectin is a potential non-invasive biomarker of infectious colitis, but it is not suitable for detection of enteritis. While practical, the use of commercially available human presents sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker.

Calprotectin (S100 A8/A9) and TNF-alpha in differential diagnosis of chronic abdominal pain in children

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0013.7957 ◽

2017 ◽

Vol 53 (1) ◽

pp. 5-10

Author(s):

Stanisław Pieczarkowski ◽

Kinga Kowalska-Duplaga ◽

Andrzej Wędrychowicz ◽

Krzysztof Fyderek ◽

Przemko Kwinta ◽

...

Keyword(s):

Differential Diagnosis ◽

Abdominal Pain ◽

Fecal Calprotectin ◽

Chronic Abdominal Pain ◽

Tnf Alpha ◽

Control Group ◽

Healthy Children ◽

Inflammatory Bowel

Introduction: Chronic abdominal pain in children is a very frequent and sometimes challenging diagnostic issue. Differential diagnosis in that cases is difficult and often connected with numerous, time-consuming, expensive, and frequently stressful diagnostic studies. The aim of the study was to establish whether fecal calprotectin concentration (FCC) and TNF-alpha may be useful in children with chronic abdominal pain to differentiate between inflammatory bowel disease (IBD), other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. Methods. The study included patients (median age 13 years), who were assigned to functional gastrointestinal disorders group (n=33); inflammatory gastrointestinal disorders other than IBD (n=71), children with IBD (n=37) and 22 healthy children served as a control group. The concertation of FCC and TNF-alpha in stool samples was measured using ELISA. Results: In healthy children and in children with functional disorders FCCs were below 100 μg/g. In patients with IBD FCCs and TNF-alpha were markedly elevated as compare to children with functional gastrointestinal disorders, however using ROC discrimination of IBD patients was significantly better using FCC than TNF-alpha. Conclusion: FCC is better test for differentiation between IBD, other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders as compare to TNF-alpha concentration in stool. FCC as screening test in patients with chronic abdominal pain should allow to diminish unnecessary diagnostic in cases of functional gastrointestinal disorders.

Burden of drug use for gastrointestinal symptoms and functional gastrointestinal disorders in France: a national study using reimbursement data for 57 million inhabitants

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819853790 ◽

2019 ◽

Vol 12 ◽

pp. 175628481985379 ◽

Cited By ~ 2

Author(s):

Philippe Tuppin ◽

Sébastien Rivière ◽

David Deutsch ◽

Christelle Gastaldi-Menager ◽

Jean-Marc Sabaté

Keyword(s):

Anatomical Therapeutic Chemical ◽

Large Population ◽

Individual Characteristics ◽

National Study ◽

Anti Inflammatory ◽

Stage Renal Disease ◽

End Stage

Background: Gastrointestinal therapeutic drugs (GTDs) are extensively prescribed. The aim of this study was to investigate the characteristics of GTD use in a large population: the French general health scheme beneficiaries (87% of the 66 million inhabitants) in 2016. Methods: The national health data system was used to identify individual characteristics, diseases and GTD classes reimbursed, together with the costs, using anatomical therapeutic chemical class. Results: Among the 57.5 million individuals included, 45% received at least one reimbursement among the 130 million prescriptions reimbursed (90% prescribed by a general practitioner): proton-pump inhibitors (PPI; A02BC: 24%), drugs for functional gastrointestinal disorders (A03: 20%), drugs for constipation (A06: 10%), antidiarrheals, intestinal anti-inflammatory/anti-infective agents (A07: 10%), antiemetics and antinauseants (A04: 7%), other drugs for acid-related disorders (A02X: 6%), other drugs for peptic ulcer and gastro-oesophageal reflux disease (A02BX: 4.5%), antacids (A02A: 1.5%). The overall cost of reimbursed GTDs was €707 million and the mean cost per user was €28. Marked variations were observed according to age, sex, and disease. The rates of at least one reimbursement among infants were A07: 28%, A03: 17%, A02BX: 9%, A02X: 7%, A02BC: 6% and A06: 5%. Women more frequently received a reimbursement than men for each GTD class. Reimbursement rates also varied according to health status (end-stage renal disease A02BC: 66%, pregnancy A03: 53%, A04: 11%), treatments (people with at least six reimbursements for nonsteroidal anti-inflammatory drugs in 2016 A02BC: 62%). Chronic GTD use (>10 reimbursements/year) was observed in 19% of people with at least one A02BC reimbursement, A02BX: 11%, A03: 7%, A04: 2%, A06: 17% and A07: 3%. Conclusions: This study demonstrates extensive and chronic use of GTD in France, raising the question of their relevance according to current guidelines. They must be disseminated to general practitioners, who are the main prescribers of these drugs.

Increased Fecal Calprotectin Is Associated with Worse Gastrointestinal Symptoms and Quality of Life Scores in Children with Cystic Fibrosis

Journal of Clinical Medicine ◽

10.3390/jcm9124080 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4080

Author(s):

Fabien Beaufils ◽

Emmanuel Mas ◽

Marie Mittaine ◽

Martin Addra ◽

Michael Fayon ◽

...

Keyword(s):

Quality Of Life ◽

Cystic Fibrosis ◽

Intestinal Inflammation ◽

Pancreatic Insufficiency ◽

Fecal Calprotectin ◽

Stool Samples ◽

Digestive Disorders ◽

Cystic Fibrosis Transmembrane

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children’s stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQLTM and the Quality of Life Pediatric Inventory 4.0-PedsQLTM. Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, “Heart Burn Reflux”, “Nausea and Vomiting”, and “Gas and Bloating”). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores.

Validation of the Pediatric Rome II Criteria for Functional Gastrointestinal Disorders Using the Questionnaire on Pediatric Gastrointestinal Symptoms

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/01.mpg.0000172749.71726.13 ◽

2005 ◽

Vol 41 (3) ◽

pp. 305-316 ◽

Cited By ~ 100

Author(s):

Arlene Caplan ◽

Lynn Walker ◽

Andr??e Rasquin

Keyword(s):

Rome Ii Criteria

Elevated fecal and serum calprotectin in COVID-19 are not consistent with gastrointestinal symptoms

Scientific Reports ◽

10.1038/s41598-021-01231-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hajar Shokri-Afra ◽

Ahmad Alikhani ◽

Bahman Moradipoodeh ◽

Farshid Noorbakhsh ◽

Hafez Fakheri ◽

...

Keyword(s):

Intestinal Inflammation ◽

Cell Damage ◽

Fecal Calprotectin ◽

Severe Illness ◽

Intestinal Epithelial ◽

Inflammation Marker ◽

Gi Symptoms ◽

The Relationship ◽

Patient Subgroups

AbstractIntestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (n = 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g; P < 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL; P < 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level.

Experimental infectious challenge in pigs leads to elevated fecal calprotectin levels following colitis, but not enteritis

Porcine Health Management ◽

10.1186/s40813-021-00228-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jéssica A. Barbosa ◽

Lucas A. Rodrigues ◽

Daniel A. Columbus ◽

Juan C. P. Aguirre ◽

John C. S. Harding ◽

...

Keyword(s):

Intestinal Inflammation ◽

Point Of Care ◽

Sandwich Elisa ◽

Fecal Calprotectin ◽

Field Application ◽

Dipstick Test ◽

Fecal Samples ◽

Brachyspira Hyodysenteriae ◽

Non Invasive ◽

Serovar Typhimurium

Abstract Background Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. Results Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method. Conclusions Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.

No Correlation between Positive Fructose Hydrogen Breath Test and Clinical Symptoms in Children with Functional Gastrointestinal Disorders: A Retrospective Single-Centre Study

Nutrients ◽

10.3390/nu13082891 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2891

Author(s):

Jarosław Kwiecień ◽

Weronika Hajzler ◽

Klaudia Kosek ◽

Sylwia Balcerowicz ◽

Dominika Grzanka ◽

...

Keyword(s):

Clinical Features ◽

Clinical Symptoms ◽

Clinical Importance ◽

Recurrent Abdominal Pain ◽

Clinical Feature ◽

Hydrogen Breath Test ◽

Fructose Malabsorption

Fructose malabsorption is regarded as one of the most common types of sugar intolerance. However, the correlation between gastrointestinal symptoms and positive results in fructose hydrogen breath tests (HBTs) remains unclear. The aim of this study was to assess the clinical importance of positive fructose HBT by correlating the HBT results with clinical features in children with various gastrointestinal symptoms. Clinical features and fructose HBT results were obtained from 323 consecutive children (2–18 years old, mean 10.7 ± 4.3 years) that were referred to the Tertiary Paediatric Gastroenterology Centre and diagnosed as having functional gastrointestinal disorders. A total of 114 out of 323 children (35.3%) had positive HBT results, of which 61 patients were females (53.5%) and 53 were males (46.5%). Children with positive HBT were significantly younger than children with negative HBT (9.0 vs. 11.6 years old; p < 0.001). The most frequent symptom among children with fructose malabsorption was recurrent abdominal pain (89.5%). Other important symptoms were diarrhoea, nausea, vomiting, and flatulence. However, no correlation between positive fructose HBT results and any of the reported symptoms or general clinical features was found. In conclusion, positive fructose HBT in children with functional gastrointestinal disorders can be attributed to their younger age but not to some peculiar clinical feature of the disease.