Faecal Lactoferrin – A Novel Test to Differentiate between the Irritable and Inflamed Bowel?

R. Sidhu; P. Wilson; A. Wright; C. W. H. Yau; F. A. D'Cruz; L. Foye; S. Morley; A. J. Lobo; M. E. Mcalindon; D. S. Sanders

Disclosures

Aliment Pharmacol Ther. 2010;31(12):1365-1370. 

In This Article

Abstract and Introduction

Abstract

Background Distinguishing between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can be challenging.
Aims To investigate the utility of faecal lactoferrin as a marker of inflammation in patients with IBD, IBS and controls.
Methods Disease activity in IBD patients was assessed using the modified Harvey–Bradshaw Activity Index. Stool samples were analysed using an ELISA assay.
Results We recruited 137 patients with IBS, 126 with ulcerative colitis (UC) and 104 with Crohn's disease (CD), and 98 healthy volunteers. The median ± IQ lactoferrin concentration (μg/g faecal weight) was 0 ± 1.4 for IBS patients, 6.6 ± 42 for UC patients, 4 ± 12.7 for CD patients and 0.5 ± 2 for healthy controls. Lactoferrin levels were significantly higher in IBD patients compared with IBS/healthy controls (P < 0.001). The median lactoferrin concentrations were significantly higher in active UC & CD patients compared with inactive patients (P < 0.001 and P = 0.002 respectively). The sensitivity, specificity, positive and negative predictive values of lactoferrin in distinguishing active IBD from IBS/healthy controls were 67% and 96%, 87% and 86.8% respectively.
Conclusions Lactoferrin is useful to differentiate between IBD and IBS, and can be used as an adjunct to blood parameters to determine IBD patients who have ongoing inflammation.

Introduction

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are common entities in the Western population.[1–3] Both conditions may present with similar clinical features such as diarrhoea and abdominal pain. Patients with IBD oscillate between periods of active and inactive disease and may even present with concomitant functional IBS. The discrimination of IBS from active IBD can be resourcefully challenging for clinicians and may delay effective treatment. Some investigations may also be perceived as uncomfortable or invasive for the patient. Clinical criteria such as ROME II IBS have been devised to aid the diagnosis of IBS.[4,5] The determination of inflammatory activity is crucial for patients with IBD for the diagnosis, monitoring and step up of therapy. Clinical indices are widely used, but are hampered by the subjective nature of symptom reporting and have been shown to be poorly correlated with mucosal activity.[6] Colonoscopy is the accepted gold standard for investigation of the colon, but is invasive and associated with risks.[7] Whilst there is emerging evidence of activation of the mucosal innate defence system toward a pro-inflammatory response in IBS patients, the absence of endoscopic and histological inflammation remains an accepted approach to the diagnosis of IBS by the bedside.[8]

Lactoferrin (LF) is an iron binding glycoprotein secreted by most mucosal membranes and a major component of secondary granules of polymorphonuclear neutrophils, a component of the inflammatory response.[9,10] Elevated LF has been used as a marker of active IBD[11–16] and for monitoring patients for response to treatment.[17] Some studies report a high sensitivity of LF for active IBD in comparison with IBS. However, the use of LF for the distinction of inactive IBD and IBS is less clear.[13,14,18,19] In Table 1, the comparative studies of patients with IBD and IBS using LF are tabulated.[11,13–16,19]

The aim of this study was to investigate the clinical utility of LF as a marker of GI inflammation in patients with active and inactive IBD compared with patients with diarrhoea predominant IBS and healthy controls.

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