May 22, 2016/Digestive

Just Breathe: Experimental Test May Ease Celiac Screening in Kids

First-ever pilot findings for CD reported at DDW 2016

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Alkhouri Naim, MD

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The workup for children who present with diarrhea, abdominal pain and weight loss often includes a screen for celiac disease, an autoimmune gluten intolerant condition affecting an estimated 1 to 5 percent of the population. This screening is typically done with blood tests and a confirmatory biopsy via upper endoscopy, a procedure that’s tough for adults to tolerate, let alone kids.

But in the future, many of those unpleasant procedures might be replaced by a simple exhalation. Volatile organic compounds (VOCs) comprising about 1 percent of the exhaled breath have been shown to correlate in unique patterns with certain disease states. By measuring these VOCs, new investigational mass spectrometry-based technology can identify these so-called “breathprints.”

Mass spectrometry, which measures differences in compounds based on their mass, charge and other characteristics, has been used for many years to assess substances in blood. “What’s new is that now we can measure them in the exhaled breath,” says Cleveland Clinic pediatric gastroenterologist Naim Alkhouri, MD.

The device used to perform the procedure is known as “selected ion flow tube mass spectrometry.” Manufactured by Syft Technologies, it is still investigational and not yet marketed anywhere.

Dr. Alkhouri and his team have previously published positive results for exhaled breath testing to detect nonalcoholic fatty liver disease. Now, at Digestive Disease Week 2016, he reported first-ever pilot study findings for celiac disease.

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Separating celiac from normal

Single exhaled breath specimens were collected from 24 patients aged 6 to 21 with a new diagnosis or untreated celiac disease and from 46 who had an existing celiac diagnosis and were treated with a gluten-free diet. Their VOC concentrations were compared with those of exhaled samples from 55 healthy controls.

A total of 16 known VOCs were significantly different in patients with both treated and untreated celiac disease compared to healthy controls, while no differences were seen between the two celiac groups.

Dr. Alkhouri and colleagues identified a combination of just three breath VOCs that could be used to classify subjects as either having celiac or a healthy control with about 94 percent accuracy. Those compounds are ethanol and trimethylamine — both associated with gut flora that is altered in celiac disease — and isoprene, an indicator of metabolic status.

“These aren’t unique compounds we’re looking at. We all make these compounds. We’re looking at the changes in the concentration in breath,” Dr. Alkhouri explains.

A Reassuring Future

Measuring exhaled VOCs isn’t expected to replace gastric biopsy for confirming a diagnosis of celiac disease, but a negative result could cut down dramatically on the number of biopsies that are needed. “It would be nice to have a sensitive test that can reassure parents that their child doesn’t have celiac,” Dr. Alkhouri notes.

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Moreover, the breath test might also replace blood tests as a way to monitor the effect of a gluten-free diet — and whether kids are actually sticking to it. “We want to see if there are biomarkers of adherence and efficacy of the approach,” he says.

Dr. Alkhouri also envisions future miniaturization of the breath exhalation technology. “The goal is to get a small device that just measures a couple of VOCs — maybe attached to an iPhone — that a primary care physician can use.”

Other research is focused on the clinical potential of measuring VOCs in substances other than breath, including stool, urine and bile acids. However, “the breath is the most exciting because it’s so noninvasive and easy.”

He cautions, though, “This is just a pilot, not ready for prime time…We know we’re not there yet.”

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