Abstract and Introduction
Abstract
Background There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease.
Aim Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD.
Methods A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed.
Results Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1β showed an inverse relation with clinical disease activity.
Conclusions Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD.
Introduction
The diagnosis and differentiation of inflammatory bowel diseases (IBD) lacks a single gold standard and takes a multimodal approach involving clinical, endoscopic, histologic, serological and radiological observations. IBD commonly suffers from a delay in time from first occurrence of symptoms to diagnosis, especially in young patients with ileal disease, which hinders our ability to alter the progression of disease. In addition, once the diagnosis of IBD is made its sub categorisation into Crohn's disease (CD) or ulcerative colitis (UC) is critical for determining the optimal treatment strategy. Even employing all currently available diagnostic modalities the sub categorisation of IBD remains elusive in about 10–15% of patients, who are then classified as indeterminate colitis or inflammatory bowel disease-unclassified (IBD-U). After defining the IBD subtype the definitive diagnosis can change, with reclassification rates as high as 10%. Treatment decisions are mainly based on clinical, serologic, radiological or endoscopic parameters, each with their obvious limitations: (i) Clinical or serological parameters of disease activity are insufficient as they only poorly correlate with intestinal disease activity and are not specific for IBD (ii) Endoscopic examination of the intestine is linked to high costs, patient discomfort, noncompliance and possible complications such as perforation and (iii) radiological procedures may be associated with interobserver and intermodality variability. It remains unclear, which patients with an initially inflammatory disease course develop into a more severe vs. benign disease phenotype. It is necessary to identify at risk populations that could benefit from a tailored therapeutic approach. The use of biological and/or immunomodulator agents for therapy might be justified early in the disease course for patients at risk for rapid disease progression. Hence, markers aiding the early and accurate diagnosis, disease course prediction or stratification are needed and would improve patient care. In this article, we review and discuss the medical literature on human breath as a novel biomarker in GI disorders, focusing on diagnosis and differentiation of IBD.