Using FoodMarble’s Handheld Breath Testers (Aire) in SIBO. A Game Changer?

Dr. Joshua Goldenberg, ND

(Naturopathic Doctor)

Goldenberg GI Center, LLC

Copyright Joshua Goldenberg. Please use slides with permission.

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FoodMarble Aire*

Validation studies and clinical applications

FoodMarble, Aire, and Aire2 are Trademarked etc. by FoodMarble (registered in Ireland with the number 574999)

QuinTron is Trademarked etc. as well

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Conflict of Interest Statement

• I have no conflicts of interest to report
• I use the Aire and Aire2 in practice but receive no payments, honoraria, etc. of any kind from FoodMarble.
• I have deferred all referral fees for any purchases made by any of my clients or patients.
• I simply find the devices useful and wish to share my experience.

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Medical Disclaimer

By use of this presentation you agree to the terms and conditions listed below.

• This presentation is not meant to replace medical advice. It is meant to provide some educational information. It cannot treat, prevent, or diagnose disease. Please, for your health, consult with a qualified medical professional for all medical matters.
• I attempt to provide education around the FoodMarble handheld Aire devices as well as SIBO and sugar malabsorption. However please be aware that research is constantly changing and only you and your medical provider can decide what is appropriate for your care and what is worth implementing.
• Do not delay or change care based on what you see here. A presentation cannot replace medical school. If you have a medical concern please see your medical provider.
• Joshua Goldenberg accepts no liability for damages associated with the use of this presentation.
• You shall defend, indemnify and hold Joshua Goldenberg harmless from all liabilities, claims, and expenses, including attorney’s fees resulting from your use or misuse of the information from this presentation.
• Please consult with your medical provider before making any health changes.

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Who Am I?

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NATIONAL UNIVERSITY OF Natural Medicine

Teacher with a focus on:

• Evidence-evaluation
• Critical review of the medical literature
• Evidence-based medicine

CAIHM

ACADEMY OF INTEGRATIVE HEALTH & MEDICINE

Dr. Journal Club

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BMJ onunm

NATIONAL UNIVERSITY OF Natural Medicine

ROME

FOUNDATION JAMA The Journal of the American Medical Association

Researcher with a focus on:

• SIBO
• IBS

UTS:ARCCIM

INTERNATIONAL COMPLEMENTARY MEDICINE RESEARCH LEADERSHIP AND CAPACITY BUILDING PROGRAM

Cochrane

Evidence-based medicine

Annals of Internal Medicine

Established In 1927 by the American College of Physicians

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GastroANP Gastroenterology Association of Naturopathic Physicians

Clinician with a focus on:

THE GOLDENBERG GI CENTER, LLC

• SIBO, IBS, IBD & GERD
• Past President of the Gastroenterology Association of Naturopathic Physicians

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What is the Aire?

• Handheld gas sensor/s linked to an app on your phone
• “Fermentation Scores” are presented
• Note this is NOT linear in Aire2
• Clinicians can see the actual ppm
• Aire measures H2
• Aire2 measures H2 and CH4
• Plans for H2S in the future (“currently under development and should be available through a software update by the end of 2022”)
• Does not measure CO2

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What is FoodMarble?

• Amazing story of a PhD engineer with a girlfriend (now wife) struggling with IBS.
• Six years and 6 million dollars in funding later the company has 25 employees and has sold over 30,000 Aire devices.

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Validation Studies

--Note most of these are industry sponsored/authored--

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Technical Performance

• MEDRXIV paper. In peer review now. 60
• Barahona et al 2022 50
• Accredited testing and calibration laboratory 40
• QuinTron vs. Aire 30
• Tested certified ppm H2 gases of 3ppm, 10ppm, and 50ppm. 20
• 3 Aires tested 3 times on 3 non-consecutive days 10
• Overall mean absolute error 1.2 ppm

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Comparison to QuinTron in Healthy Participants (Orocecal time) • Shortt et al 2019 Poster

• N=14 healthy adults

• Each participant compared two Aire devices to QuinTron Device

• Lactulose (10g); 3-hour test

• Breath tests q5min switch between the 3 devices x 3 hours

• Malabsorption defined as >=/= 20 ppm increase in H2 over baseline (so really just measuring orocecal time?)

• Of 14 one had baseline H2 over 15 so excluded

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RESULTS:

• One did not have a 20+ rise within 3 hours (slow transit)
• Of the 13 included, all had congruence within 10 min – hitting the 20 point rise all lined up with both Aire and the QuinTron

(1) There was diagnostic agreement in all cases

(3) Comparison of interpolated H concentrations

One volunteer was excluded due to a high H baseline, leaving 13 volunteers for the final analysis;

One volunteer did not display malabsorption (<20ppm rise in breath H2) with the 3 hour testing period;

• 12 volunteers displayed malabsorption (>20ppm rise in breath H2) with the 3 hour testing period.

to 0o 10 33.29 10640 11:40 12:12:21 10:33.21 10040 1140 12:1320 12:4E-40

TIME

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UTILITY OF A CONSUMER-FRIENDLY PORTABLE HYDROGEN BREATH ANALYSER DEVICE FOR MONITORING COLONIC FERMENTATION AND SENSATION IN RESPONSE TO SUPPLEMENTAL FIBER

Claire Shortt, Niall McGovern, Eoghan Lafferty, Pankai I. Pasricha

BACKGROUND

Fermentation of soluble fibers by fecal microbiota is vital for colonic health and leads to production of hydrogen (H2) and other volatiles. On the other hand, excessive or aberrant fermentation is associated with gastrointestinal distress. There are currently no practical methods for monitoring fermentation in the gut. To address this need, we developed a handheld breathalyzer device linked to a smartphone (AIRE, FoodMarble, Dublin, Ireland) and validated its utility to measure breath H2 and associated symptoms in response to supplemental fiber.

METHOD

We studied 20 subjects (15 healthy, 5 IBS) in a double-blind, randomized, crossover design (1-week baseline, 2-weeks 1st fiber, 2-week wash-out, 2-weeks 2nd fiber, 1-week washout) using 2 different prebiotics: a galacto-oligosaccharide (GOS) and a wheat dextrin (WD) fiber. 6-9 breath measurements were made daily along with scoring bloating, flatulence and abdominal pain, on a 0-10 scale. Data was analysed using 2-way ANOVA and Pearson's correlation and linear regression as appropriate.

RESULTS

Interim results show that for the group as a whole, both prebiotic fibers produced a highly significant change in breath H2 compared to baseline, for both week 1 and 2 (Figure 1). After discontinuation of the prebiotic, H2 values returned to baseline. There were no statistically significant differences between the H2 levels in weeks 1 and 2 for the two prebiotics. However, there was large inter-subject variability in the individual responses.

Study

Crossover RCT design

Population

N=20 (15 healthy, 5 IBS)

Intervention

GOS, wheat dextrin

Control

Crossover w/ washouts

Outcomes

Symptoms and ppm H2

We next examined patient-reported sensation which was mild and comparable in both groups, with no overall change in either prebiotic group, compared to baseline period (GOS versus WD: "pain"= 0.7 vs. 0.65; bloating = 1.45 vs. 1.41; flatulence NS for all). Nevertheless, there were significant correlations between breath H2 and "pain" (r=0.18; P=0.02), bloating (r=0.31; p <0.0001) and flatulence (r=0.49; p <0.0001).

CON monitor breath H2 levels along with subjective symptoms, detecting the expected increase in colonic fermentation by supplemental fiber before returning to baseline after discontinuation. This device may enable the consumer to monitor the activity of their own microbiota in response to fiber or fermentable foods (such as FODMAPs) and potentially titrate the quantity in an objective, quantifiable and personalized manner. The correlation analysis also suggests that colonic fermentation can be sensed by consumers, even at subclinical levels. While further studies are needed, this device may enable more accurate detection of symptoms in a number of patient populations including IBS and small intestinal bacterial overgrowth.

Shortt et al 2020 (DDW poster)

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Comparison to QuinTron in suspected SIBO Participants

• MEDRXIV paper. In peer review now.
• Barahona et al 2022
• 36 pts suspected of SIBO
• LBT done with QuinTron and Aire
• Diagnostic agreement 31/36=86%

Table 1. LHBT comparison of AIRE and mail-in kit (n=36).

Table 2. Mean baseline, overall and peak breath H2 ppm for AIRE devices and mail-in kits (n=36).

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Comparison to QuinTron in Suspected SIBO Participants

• It appears the mail ones are running lower which may be due to gas leakage in the bags over time — Positive Criteria (CH4)
• In general looks similar but if anything more positives with Aire 40
• Of the 3 ‘extra’ positive cases with Aire, two responded to abx treatment, one result pending. (Barahona 2021)

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Comparison to QuinTron in Participants with Suspected Lactose Malabsorption

• Shrestha 2019
• 75% of world population has limited expression of beta-lactase - a proportion of which will experience adverse GI sx from lactose when the amount ingested exceeds the enzymatic capacity of the residual intestinal lactase activity.
• According to Aire paper a positive is a rise of 25 ppm with 50 g lactose at any time
• According to Dynamed a positive is a rise of 20 ppm with 25 g lactose within 3 hours
• SIBO can cause false positive (or have both)

Participants

Cohort Measures

AIRE versus QuinTron (Aire used the arbitrary units (AU))

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Results

• Strong correlation with lactose (r=0.82; P<0.001) and milk ingestion (r=0.90; p<0.001)

• Baseline and maximum levels don’t line up very well. But overall very correlated

• I am a bit curious about the AU conversion messing with the extremes. Perhaps if you had the true ppm there would be better correlation there too. But perhaps be wary at extreme values

• They calculated 3 AU as equivalent to 25ppm. Of the 12 suspected LI individuals, there was baseline data for ten. Nine tested pos for LM with Quintron and all ten did with AIRE

“lactose intolerance study was unknown to us, found out when published”

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Aire2 validation studies

• In process according to the company

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Important Notes

• Fermentation scores are not in linear relationship to ppm
• Need to have clinician dashboard to see ppm
• Will need Rx for lactulose
• Hard to get multiple packets of fructose/lactose for SIBO testing. Company says may make them more available in the future.
• Calibration (how is it calibrated? Degrades over time?) FoodMarble: “Each unit is uniquely calibrated using gas standards and then sensor drift over time is managed remotely using a machine learning approach”
• Correction factor not needed
• Need minimum of 15 min between tests (issue for sequential testing)

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Clinical applications

• Food and symptoms exploration
• ’Matt Method’
• Lactose/Fructose malabsorption testing
• Formal SIBO testing
• Spot testing to track progress
• AUC analysis

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Food and symptom exploration

• Can track F scores with various foods and look for association between symptoms and gas levels.
• Recall that gas may be from fermentation anywhere along the GI track (i.e. from dinner last night)
• Foodmarble’s ‘Food Intolerance Kit’
• ‘Matt Method’: Intermittent fasting 16 hours. Breakfast with challenge of known Ok foods plus one new variable. Test for up to 3 hours. Then eat as you will through the rest of the day. With each new tested variable add this to green food list or red food list and continue testing new variable each am for breakfast until you have a good sense of ok foods and foods to avoid.

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Lactose/Fructose Malabsorption Testing

• Can do formal lactose/fructose malabsorption testing
• Lactose 25g, fructose 25g (mixed with or followed by one cup of water) (NA Consensus, Rezaie 2017)
• Note that the ‘challenge pack’ has 25g of fructose and lactose
• Recall that malabsorption is not the same as intolerance. It needs to cause symptoms to be intolerance
• Fructose and lactose breath testing should be performed for at least 3 hours (NA Consensus, Rezaie 2017)
• The presence of bacterial overgrowth should be ruled out before performing lactose or fructose breath testing (NA Consensus, Rezaie 2017)

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9:594

Formal SIBO Testing

Discovery

Challenges

Results FAQ

• Recall: Barahona et al 2021
• No validation study yet for the methane sensor
• Nothing for H2S SIBO yet
• Can get Rx for lactulose (10g in 15 ml solution)
• 75g glucose OTC (proximal SIBO only?)
• Can even use the fructose packet in the ‘challenge kit’ (false positive with fructose intolerance?)

Fructose, the fruit sugar, is hard to absorb in large quantities. Fructose is found in large quantities in fruit, but also in lots of other natural and processed foods. Some people can absorb fructose better than others, which is why it's important to measure how well you can do it. Your ability to absorb fructose can go down temporarily when the body is under stress, so it's important to relax before, during and after eating. Fructose can be fast-tracked into the body by pairing up with glucose, so foods high in both are generally easier to digest.

Schedule

Start

81

Home Discovery Foods Profile

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Formal SIBO Testing

Magical Ingredients for the Modern Cook

modernist

ptr

Kitchen Alchemy

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Spot Testing to Track Progress

• In a patient with high SIBO levels I will start an intervention and then ask them to do a spot test once a week.
• I ask them to pick the same day of the week each time eat the same dinner the night before and breakfast and test using the breakfast as the challenge.
• I would like to see a steady decrease in gasses each week and if it starts plateauing we would do a formal challenge (SIBO test) to confirm.
• This is useful clinically in theory and easier on patients than doing a bunch of challenges.

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Clinician Dashboard

FoodMarble

Hi, Dr Goldenberg

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Challenges

Day To Day

Patient load

Challenges Completed

Here are all the challenges that have been completed by this user. Click any of the rows below to view a chart of the results.

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Clinician Dashboard

Home

Challenges

Day To Day

Patient

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FoodMarble

Lactulose Challenge Result

Date: 05/17/2022

Clinician Name: Dr Goldenberg

Email: drg@goldenberggicenter.com

Results

Hydrogen

Baseline: 6 ppm (LOW)

Rise in 90 min: 47 ppm (HIGH)

Peak in 90 min: 53 ppm after 21 min

Methane

Baseline: 33 ppm (HIGH)

Rise in 90 min: 2 ppm (HIGH)

Peak in 90 min: 35 ppm after 52 min

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AUC Analysis

• New feature in the works for clinician dashboard

• Case example. Pre/Post testing (lactulose) for a rifaximin intervention

• Hydrogen worse? Methane better? Overall improvement or worsening? Bail or stay the course?

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AUC Analysis

• What was at first a confusing gas response is now clearer -> overall drop of 20ppm H2 equivalent. A positive gas response.

• Don’t bail!

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Important

• Fermentation scores DO NOT equal ppm!
• Nor are they in a linear relationship especially in Aire2
• High levels (>25ppm) in either gas can throw the overall “F” score
• For example, in trying to track the impact of oral methanogens on a patient with a high baseline methane (Erdrich 2021) a patient recorded a 6 before and then a 2 after chlorhexidine mouthwash for her methane ‘Fermentation score’ (out of 10). This looked like oral methanogens were dramatically impacting results, but when I checked the ppm, they were actually 31 ppm and 31 ppm both times! NO CHANGE and we could stick with future testing without mouthwash.
• FoodMarble is aware of this issue and is planning to change their calculations for Fermentation Scores

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Pros

• Relatively cheap device that can be used hundreds of times allows for real life H2 and CH4 testing
• In small congruence testing Aire appears to perform similarly to Mail-ordered tests in healthy, SIBO suspected, and lactose intolerance suspected populations
• Allows for cheap and timely repeat testing, which is essential to good SIBO care in my opinion.
• Good for a ‘have it at the ready if you get nervous’ purpose for those in remission I simply find the devices useful and wish to share my experience.
• Clinician dashboard is excellent
• New features rolling out
• A small startup company but extremely responsive
• The company is clearly dedicated to a research focused approach

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Cons

• SO MUCH DATA. Hard for some patients to tell the forest from the trees
• Can’t do H2S
• Patients/clients can’t see ppm
• It appears that (all?) the studies were industry sponsored although perhaps not all from FoodMarble.
• Can we trust the CH4 data? Validation studies are still pending

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So... Game Changer?

• I think so!
• Bearing in mind all the caveats mentioned previously, this technology allows for cheap and timely repeat testing which has lowered the barriers to ideal SIBO monitoring in my practice.
• However, formal research on these devices is minimal and there are significant gaps particularly with the Aire2. So while I have embraced this technology I remain vigilant in terms of potential findings from future research or issues with clinical interpretation.

FoodMarble, Aire, and Aire2 are Trademarked etc. by FoodMarble (registered in Ireland with the number 574999)

QuinTron is Trademarked etc. as well

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Questions & FoodMarble’s Answers

Clinician Dashboard

• “Yes, the clinical dashboard is out of beta but we are always adding new features to improve the clinician experience and data interpretation abilities. The dashboard is free of charge for clinicians... We don’t ask for people to submit their credentials. We do ask for a profile or company page so we can get a sense of them.”
• We have recently created FoodMarble Classroom which provides guidance on data interpretation and has been particularly helpful for those new to breath testing.
• We also are creating a platform called FoodMarble Connect which is a database of clinicians who are already set up with FoodMarble. We have over 30k users and many of these are working without a clinician. However, very frequently we get asked to recommend a clinician to help them. Interested clinicians can sign up and we will make this database available to all of our existing and future users.

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Questions & FoodMarble’s Answers

Will end-users (customers/clients) be able to see ppm at any point or will you stick to fermentation scores?

• The direct-to-consumer device, AIRE, is designated a wellness device by the FDA, which basically means the device can be used for maintaining or encouraging a healthy lifestyle and is unrelated to the diagnosis, cure, mitigation, prevention, or treatment of a disease or condition.
• MedAIRE is listed as a medical device with the FDA, which is considered a tool to aid the clinician in the diagnosis of carbohydrate malabsorption or SIBO. We are currently getting advice on this from legal counsel, however, we hope to show ppm values to patients (and possibly consumers), if allowed by the FDA. It’s a grey area!
• In the meantime, we also plan to split the Fermentation Score, to show one relating to each gas. This should help users track how each gas is changing over time.

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Questions & FoodMarble’s Clinician Dashboard Home

Loving the AUC approach and can use the excel you sent me. You mentioned this might be rolled out on the clinician dashboard.

• As mentioned above, we will offer a report to help assess changes and response to treatment. AUC seems like a useful measure to include.
• We are also adding medication tracking to the app, which will be helpful when tracking response to treatments over time.

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Questions & FoodMarble’s Clinician Dashboard

Answers

Time Series Data

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Questions & FoodMarble’s Answers

GastroANP

Gastroenterology Association of Naturopathic Physicians

Correction factors based on CO2 levels. Am I correct in understanding that you don’t need to do this because the device measures after a certain number of seconds of blowing ensuring the measurements are indeed from alveolar air?

• A high-quality end-tidal breath sample is required for a reliable breath test result. In the case of AIRE, the user is instructed to hold their breath for three seconds before exhaling in order to promote adequate gas exchange in the lungs. Upon exhalation, the user is instructed to breathe slowly into the mouthpiece for five seconds. The sensor in the AIRE device performs optimally with a steady flow of breath and once the patient starts to exhale, readings are recorded continuously throughout the five seconds.
• The proprietary algorithm selects the end-tidal breath sample and is recorded in ppm. If a patient stops breathing before five seconds have been reached, they will be asked to retake the breath sample one minute later.

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Questions & FoodMarble’s Answers GastroANP Gastroenterology Association of Naturopathic Physicians

What is MedAire versus Aire?

• MedAIRE (H2 only) and MedAIRE2 (H2 and CH4) are FDA-listed devices. There are minor differences between these and the direct-to-consumer devices. The key difference is that if a clinician wants to submit reimbursement, they must use a medical device. The colour of the device, packaging, and inner materials differ slightly (attached to the email). The Healthcare app only works with users who are linked to a dashboard account as a patient, whereas the direct-to-consumer app can work with consumers and patients. If a user is working with a doctor (linked to the dashboard as a patient), the app will provide access to SIBO tests (glucose and lactulose), and will not share test results with the patient, only the doctor. The pricing also differs slightly between the two and depends on volume.

Association of Naturopathic Physicians

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Citations

• Barahona, Guillermo; Moran, Áine; Bride, Barry; Villatoro, Luisa; Burns, Robert B; Konings, Bo; et al. S1377 Postprandial Breath H2 Using a Portable Handheld App-Connected Device to Predict the Presence of Small Intestinal Bacterial Overgrowth as Well as the Response to Antibiotic Treatment, The American Journal of Gastroenterology: October 2021 - Volume 116 - Issue - p S632
• Barahona, Guillermo; Barry McBride, Áine Moran, Sahar Hawamdeh, Luisa Villatoro, Robert Burns, et al. Improving the Diagnosis of Small Intestinal Bacterial Overgrowth Using an At-Home Handheld App Connected Breath Analysis Device (AIRE). medRxiv 2022.04.21.22274143
• Erdrich, Sharon, Edwin C K Tan, Jason A Hawrelak, Stephen P Myers, and Joanna E Harnett. 2021. Hydrogen – Methane Breath Testing Results Influenced by Oral Hygiene. Scientific Reports, 1–11.
• Rezaie, Ali, Michelle Buresi, Anthony Lembo, Henry Lin, Richard McCallum, Satish Rao, et al. 2017. “Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus.” The American Journal of Gastroenterology 112 (5): 775–84.
• Shortt C, Brief J. PWE-098 A pilot validation study of an at-home hydrogen breath test device. Gut 2019;68:A219.
• Shortt, Claire et al. “Mo1958 UTILITY OF A CONSUMER-FRIENDLY PORTABLE HYDROGEN BREATH ANALYSER DEVICE FOR MONITORING COLONIC FERMENTATION AND SENSATION IN RESPONSE TO SUPPLEMENTAL FIBER.” Gastroenterology 158 (2020) Goldenberg Gl Center, LLC
• Shrestha A, Prodhan UK, Mitchell SM, Sharma P, Barnett MPG, Milan AM, Cameron-Smith D. Validity of a Portable Breath Analyser (AIRE) for the Assessment of Lactose Malabsorption. Nutrients. 2019 Jul 17;11(7):1636.