Evaluation of Faecal Volatile Organic Compounds in the Diagnosis of Paediatric Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a growing and significant problem in childhood. The diagnosis and monitoring of IBD in children is highly invasive and is accompanied by risk, stress/anxiety for children and families and significant use of healthcare resources. Children, young people and families have told investigators that a non-invasive diagnostic test is a priority for the NHS.

IBD is an incurable chronic, relapsing condition of unknown aetiology. Its frequency has increased markedly across the world in recent years with the highest prevalence reported in Europe (322/100,000 population for CD; 505/100,000 for UC). A marked increased incidence has been seen in children especially in the Northern Hemisphere and largely due to an increase in Crohn's disease. Up to 25% of IBD starts in childhood or adolescence.

Early-onset IBD, possibly due to inheritance of a greater number of susceptibility genes and/or earlier exposure to environmental triggers, differs from that occurring in adults. In children, inflammation occurs most commonly in the colon complicating differentiation between CD and UC. Early-onset CD is more common in boys (whereas adult-onset disease occurs more commonly in females) and tends to be more extensive with greater involvement of the upper intestine. Colonic inflammation in children with UC also tends to be more extensive than in adults.

At initial presentation in all suspected children, upper and lower intestinal endoscopy (requiring two days of bowel cleansing and usually a general anaesthetic) and small bowel imaging by magnetic resonance enterography or wireless capsule endoscopy are required. Although serious adverse events are uncommon, these invasive investigations are highly stressful for children and their families and consume considerable hospital resources. Undertaking these investigations delays diagnosis and the start of treatment.

Accurate, non-invasive, rapid and cost-effective diagnostic tools that can be used in the clinic or ward setting and better means of differentiating CD from UC are needed. Faecal calprotectin (FC), a non-specific marker of intestinal inflammation, is recommended by NICE to distinguish IBD from non-inflammatory gut disorders such as irritable bowel syndrome (https://www.nice.org.uk/guidance/dg11) and a near-patient test has been developed (http://www.buhlmannlabs.ch/core/quantum-blue/calprotectin/). A recent meta-analysis (394 IBD/321 non-IBD controls) reported a pooled sensitivity and specificity of FC in the diagnosis of IBD in children of 0.98 (95% confidence interval: 0.95-1.0) and 0.68 (0.50- 0.86) respectively. The low specificity indicates that an alternative or additional test with higher specificity is needed to reduce the time to diagnosis and avoid many children undergoing unnecessary investigations.