Satya Kurada

Review article: breath analysis in inflammatory bowel diseases

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.

Association between tree pollen counts and asthma ED visits in a high-density urban center.

Background. Asthma exacerbation patterns are cyclic in nature and often correlate with air particle concentrations. Objective. To examine the relationship between asthma-related emergency department (ED) visits and outdoor air quality for pediatric and adult patients in a high asthma prevalence area, the New York City borough of the Bronx. Methods. Numbers of daily asthma-related adult and pediatric ED visits during one complete year (1999) were obtained from the seven major Bronx hospitals. Daily values of nitrogen oxides (NOx), ozone (O3), sulfur dioxide (SO2), and pollen counts were acquired. Results. Asthma-related ED visit numbers were highest in December–January and lowest in July. There were three distinct peaks of increased asthma ED visits: winter (December–January), spring (late April–May), and fall (October). The spring peak was the most striking and coincided with high tree pollen counts (tree pollen: r = 0.90, p = .03). We observed a positive correlation between asthma ED visits in the winter and SO2 and NOx levels. Winter peaks of SO2 and NOx in early December appeared to precede the winter asthma peak. Conclusions. The spring asthma peak is closely associated with increased tree pollen counts, and the asthma increase at this time is likely due to allergic reactions to pollen. No significant associations could be established with the fall peak. The winter peak correlates with elevated SO2 and NOx levels.

Current and novel therapeutic strategies in celiac disease.

ABSTRACT Introduction: A gluten free diet (GFD) is the only available treatment for celiac disease (CD). However many patients fail to respond fully clinically or histologically. Several surveys highlight the psychosocial implications of adherence to a GFD. Hence, efforts are ongoing to develop therapeutic strategies beyond a GFD. Areas covered: We conducted a search of PubMed and clinicaltrials.gov to extract articles on CD using keywords including ‘celiac disease’ and ‘refractory celiac disease’ (RCD) and focused on articles conducting pathophysiologic and therapeutic research in/ex-vivo models and human trials. We highlight novel therapeutics that manipulate these mechanisms including tight junction regulators, glutenases, gluten sequestrants and immunotherapy using vaccines, nanoparticles that may serve as adjuncts to a GFD or more ambitiously to allow for gluten consumption. We also highlight the role of anti-inflammatories, immunosuppressants and monoclonal antibodies in RCD. Expert commentary: Therapeutics including tight junction regulators, glutenases have the potential to be approved for non-responsive CD or as gluten adjuncts. We expect results of various phase 1/2 trials using AMG 714, BL 7010, IgY antibodies to be published. In the interim, off-label use of 5 amino-salicylates, budesonide, nucleoside analogues and newer biologics developed for other inflammatory diseases will be used in RCD.

Efficacy, Safety, and Long-term Outcome of Serial Endoscopic Balloon Dilation for Upper Gastrointestinal Crohn’s Disease-associated Strictures—A Cohort Study

Background Gastric and duodenal Crohns disease [CD]-associated strictures are rare. Evidence on endoscopic balloon dilation [EBD] of upper gastrointestinal [GI] CD strictures is limited, in particular in respect to serial dilations. Methods Prospective short- and long-term outcome data as well as complication rates on a cohort of upper GI CD-associated stricture dilations [stomach and duodenum] were collected from 1999 to 2015. Factors linked with clinical and technical success, long-term efficacy and complication rates were investigated. Results A total of 35 CD patients with symptomatic CD-associated upper GI strictures [20% gastric, 67% duodenal, 11% both; mean age at diagnosis 25 years; mean CD duration to stricture 79.9 months; median post-dilation follow-up 22.1 months] underwent a total of 96 pneumatic dilations [33 gastric and 63 duodenal]. The median maximal dilation diameter was 15 mm. Technical success was achieved in 93% and clinical success in 87%, with a complication rate of 4% per procedure. The mean time to re-dilation was 2.2 months and mean time to stricture-related surgery after first dilation was 2.8 months. There was no difference in short-term efficacy, safety, or long-term outcome between the first and any later dilation procedure in the same patient. Conclusions Pneumatic dilation of upper GI CD-associated strictures has a high rate of short-term technical and clinical success, with moderate long-term efficacy and acceptable complication rates. Serial dilations do not change the efficacy and could be a feasible option to delay or prevent surgical intervention.

A Distinct Colon-Derived Breath Metabolome is Associated with Inflammatory Bowel Disease, but not its Complications

OBJECTIVES:The accuracy of available noninvasive biomarkers for diagnosis, stratification, and prediction of inflammatory bowel disease (IBD) courses is limited. We analyzed volatile organic compounds (VOCs) in the breath of IBD patients and controls for diagnosis and differentiation of IBD as well as their link with disease location, activity, and phenotype.METHODS:A prospective study of diagnostic testing was conducted, recruiting Crohn’s disease (CD), ulcerative colitis (UC), other inflammatory gastrointestinal diseases (OGDs), and healthy controls (HCs), as well as subjects with ileal pouch anal anastomosis (IPAA). The breath VOC profile was analyzed using selective ion flow tube-mass spectrometry.RESULTS:One hundred and twenty-four subjects (n=24 CD, n=11 UC, n=6 OGD, n=53 HC, n=30 IPAA) were included. The breath metabolome was significantly different in patients with IBD, CD, or UC compared with OGD and HC (7 out of 22 VOCs), but not between CD and UC. No link between the level of VOCs with complications, disease location, and clinical or radiologic disease activity, as well as lab parameters or type of medication was found. Breath VOCs were markedly different in patients with IPAA compared with any other group (17 out of 22 VOCs) and the presence of pouch inflammation did not alter the VOC levels.CONCLUSIONS:A specific breath metabolome is associated with IBD and markedly changes in patients with IPAA. Analysis of a broader spectrum of VOCs can potentially aid in the development of breath prints to diagnose or differentiate inflammatory bowel disorders.

Letter: volatile metabolomics of exhaled breath or faecal gas? – authors' reply

*Department of Hospital Medicine, Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Department of Pediatric Gastroenterology, Cleveland Clinic Children’s Hospital, Cleveland Clinic Foundation, Cleveland, OH, USA. Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Department of Pulmonary Diseases, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. E-mail: florian.rieder@t-online.de

Low testosterone in non-responsive coeliac disease: A case series, case–control study with comparisons to the National Health and Nutrition Examination Survey

BACKGROUND Adults with coeliac disease (CD) often report persistent fatigue, even when CD appears well controlled for unknown reasons. AIMS To evaluate common indications for testosterone panel (TP) testing and prevalence of low testosterone (T) in CD. METHODS In our case series, we determined common indications for checking TP in CD. Next, we conducted a case-control study to compare TP in CD vs. healthy controls (HC). We compared mean total T (TT), free T (FT) based on serologic, histologic disease activity. Finally, we assessed TT in tissue transglutaminase (tTG)+ vs. tTG- subjects and CD vs. HC obtained from the National Health and Nutrition Examination Survey (NHANES). RESULTS 53 coeliac males had TP tested. Common indications included osteoporosis and fatigue. Low FT was observed in 7/13 men with osteoporosis and 5/6 with fatigue. In our case-control study (n=26 each), there was no difference in mean TT or FT between CD vs. HC, tTG+ vs tTG- or Marsh 0 vs. Marsh 3 groups. NHANES data showed no difference in mean TT between tTG+ vs tTG- (n=16 each) or CD vs. HC subjects (n=5 each). CONCLUSIONS Low T occurs in CD patients at a similar rate as the general population. Common presentations of low T may mimic non-responsive CD symptoms.