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Aeonose breath analysis on TB screening South Africa

This year, the Union World Conference on Lung Health was held in Hyderabad, India. At the TBScience pre-conference, an official event entirely devoted to basic and translational tuberculosis (TB) research, study results were presented on the Aeonose exhaled-breath tests in Cape Town.


It shows the Aeonose may be useful as a triage test for tuberculosis in HIV-infected and uninfected persons as it meets the FIND/WHO minimum Target Product Profile (TPP) for a rule-out TB test.



An exhaled-breath screening test for the detection of active pulmonary tuberculosis in patients presenting to primary health care clinics in Cape Town, South Africa.

Aliasgar Esmail, Keertan Dheda, Muhammed Dhansay


Introduction: GeneXpert Ultra is unsuitable for community-based mass screening and in up to one-third of patients an adequate sputum sample is unavailable. By contrast, the analysis of exhaled breath obtained by the Aeonose-TB device has the potential to provide an easy, onsite, rapid, and non-invasive diagnosis of tuberculosis. Thus, it may serve as a useful community-based triage tool (a major unmet need in the TB field).


Methods: We enrolled 1,143 participants (31% HIV- infected) with suspected TB (243 microbiologically-con- firmed TB, 130 probable TB, and 770 non-TB) from primary care clinics in Cape Town, South Africa. Sputum GeneXpert MTB/RIF and/ or culture served as the reference standard. Volatile organic compounds in exhaled-breath were detected using an electronic nose containing 3 metal-oxide sensors (AeonoseTM, Zutphen, The Netherlands). Data were analysed by machine learning using artificial neural networks (ANN) in a ‘leave-10%-out’ cross-validation training set (n=756; 189 TB and 567 non-TB) and the findings ratified in a test set (n=257).


Results: In the training set the sensitivity, specificity, PPV, NPV of Aeonose-TB (95% CI) was 81% (74-86) and 60% (55-64), 40% (35-45), and 90% (87-93), respectively. However, in HIV uninfected patients, using a ANN- derived rule-in threshold, performance characteristics were 59% (50-69), 91% (87-93), 68% (58-77), and 87% (83-90), respectively. In the same group, using an ANN- derived rule-out threshold, the performance characteristics were 90% (83-95), 59% (54-65), 43% (36-49) and 95% (91-97), respectively. Results in the validation set, and in HIV-infected persons, showed comparable performance characteristics.


Conclusion: Aeonose-TB may be useful as a triage test for tuberculosis in HIV-infected and uninfected persons as it meets the FIND/WHO minimum Target Product Profile (TPP) for a rule-out TB test. However, it may also have utility to rule in TB in sputum scarce or smear-negative persons. Further studies are now required to clarify these findings.

Aeonose breath analysis on TB screening Peru

The Union World Conference on Lung Health 2019 was held in Hyderabad (India) from October 30 – November 2. Dr. Ruvandhi Nathavitharana (Harvard University) presented results on the Aeonose exhaled-breath TB-study in Lima, suggesting Aeonose may meet WHO triage test criteria to rule out TB (90% sensitivity, 70% specificity) in lower-risk patients admitted with cough or TB risk factors.

Improving lung cancer screening results

At the ERS Conference in Madrid (September 28 – October 2, 2019), Sharina Kort (MST, Enschede, the Netherlands) presented clinical study results on diagnosing lung cancer using the Aeonose:

  1. Improving lung cancer diagnosis from exhaled-breath analysis by adding clinical parameters to the artificial neural network (oral presentation)
  2. Combining exhaled-breath analysis data with clinical parameters to improve the diagnosis of lung cancer (poster presentation)

Combining the electronic nose data and easily-available clinical parameters, she obtained a sensitivity of 96% and a negative predictive value of 93%. Nice results!

Pancreas new diagnostics

Improved diagnostics for pancreatic diseases are badly needed. An electronic nose (AeoNose™) analysing exhaled breath was successfully used to distinguish between pancreas carcinoma, chronic pancreatitis (inflammation of the pancreas), and healthy controls: promising results from a multicenter pilot study in the Netherlands.

Pancreatic ductal adenocarcinoma and chronic pancreatitis may be diagnosed by exhaled-breath profiles: a multicenter pilot study

Presentations at DDW San Diego

At the Digestive Disease Week in San Diego, 4 posters were presented discussing ongoing clinical studies with the Aeonose for exhaled-breath analysis:

  • Colorectal cancer and advanced adenomas
  • Barrett’s esophagus (presented both by Radboud University (Nijmegen, the Netherlands) and Mayo Clinic (Rochester))
  • Fasting state

Mo1003 — 2019  AGA
Kelly v. Keulen1, Maud E. Jansen2, Ruud W. Schrauwen3, J.J. Kolkman2,4, Peter D. Siersema1


Sa1136 — 2019  AGA    Poster of Distinction 
Yonne Peters1, Ruud W. Schrauwen2, A.C. Tan3, Sanne Bogers2, Bart de Jong1, Peter D. Siersema1


Sa1153 — 2019  AGA   
Juan Reyes Genere1, Kavel Visrodia2, Liam Zakko3, Bryan Linn1, Magdalen A. Clemens1, James Allen1, Lori S. Lutzke1, Kenneth K. Wang1


Mo2053 — 2019  AGA   
Juan Reyes Genere1, Liam Zakko2, Kavel Visrodia3, Magdalen A. Clemens1, James Allen1, Bryan Linn1, Lori S. Lutzke1, Kenneth K. Wang1

Paper on wound-swaps

The majority of clinical studies has been based on exhaled-breath analysis, but for the current study, a dedicated eNose-device was used, ‘Aetholab’, that enables headspace analysis of 4 vials simultaneously. For this purpose, 4 electronic noses have been integrated. Data analysis methods in this case are similar to the ones used in exhaled-breath analysis.

Our first paper on headspace analysis for human diagnostics was recently published in the journal ‘Clinical Microbiology and Infection’:

‘Differentiation between infected and not infected wounds using an electronic nose’

Pilot Study: Detection of Prostate Cancer



Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN).



To determine whether exhaled-breath analysis using a handheld electronic nosedevice can be used to discriminate between VOC patterns between PCa patients and healthy individuals.


Design, setting, and participants

This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE).


Outcome measurements and statistical analysis

Patient characteristics were statistically analyzed using independent sample ttest and Pearson’s chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method.


Results and limitations

Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval [CI] 0.66–0.94) and 0.70 (95% CI 0.55–0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size.



Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis.


Patient summary

We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals.



Prostatic neoplasms; Electronic nose; Volatile organic compounds; Breath tests