Diagnosing RA Using Breath Analysis of Volatile Organic Compounds

An "electronic nose" device utilizing gas chromatography and mass spectrometry may be able to identify the exhaled breath fingerprints of patients with rheumatoid arthritis and psoriatic arthritis with moderate accuracy.

The use of breath analysis by an “electronic nose” device utilizing gas chromatography and mass spectrometry can identify disease-specific volatile organic compounds (VOCs) to possibly differentiate patients with active rheumatoid arthritis (RA) from patients with active psoriatic arthritis (PsA) and healthy control subjects, according to data published in Plos One.1

The electronic nose (Cyranose 320; Smiths Detection, Pasadena, CA) allows “high-throughput analysis of mixtures of gases representing an innovative method to measure the complete spectrum of [VOCs] as a composite fingerprint,” the authors of the study wrote.

Researchers compared the exhaled breath of 21 patients with RA, 18 patients with PsA, and 21 healthy control patients using an electronic nose. The breath prints were analyzed with principal component analysis, discriminant analysis, and the area under the receiving operating characteristics curves (AUC).

The researchers also examined the relationship between breath prints and markers of disease activity and identified VOCs with gas chromatography and mass spectrometry.

The electronic nose distinguished RA patients from the control subjects with a 71% accuracy (AUC: 0.75; 95% confidence interval [CI], 0.60-0.90) and distinguished PsA patients from control subjects with 69% accuracy (AUC: 0.77; 95% CI, 0.61-0.92). The device also differentiated exhaled breath of RA and PsA patients with an accuracy of 69% (AUC: 0.72; 95% CI, 0.55-0.89).

There was also a positive association between disease activity scores (DAS28) and the number of painful joints among RA patients. The gas chromatography and mass spectrometry identified seven VOCs that differ among the three cohorts, five of which were lower in RA patients than in PsA patients.

The authors conclude that the electronic nose device “could possibly provide an additional tool in the diagnosis of inflammatory joint diseases. The data presented warrant external validation of this tool by testing its diagnostic accuracy prospectively in a large untreated group of patients with signs and symptoms of joint inflammation.

Summary and Clinical Applicability

VOCs are developed from many metabolic and inflammatory processes inside the body, and can be found in exhaled breath. The electronic nose device has the potential to be a diagnostic tool, due to its potential to analyze the complete VOC spectrum, and because collecting exhaled breath is a noninvasive procedure for patients.

The results showed that the electronic nose device can distinguish the exhaled breath of RA, PsA, and control patients with moderate accuracy. The researchers of the study suggest that further research be conducted to test the diagnostic accuracy of the device in a population of untreated patients who could be diagnosed with inflammatory joint diseases.

Limitations and Disclosures

This study was not able to assess whether baseline study participant characteristics like age and pharmacotherapy use influenced breath profiles as opposed to inflammatory disease state.

These findings have to be independently duplicated and validated in a larger sample, however it should be noted that the methodology of collecting samples must be standardized to minimize the degree to which collection may affect breath analysis.

Several authors have disclosed employment with GlaxoSmithKline.


Brekelmans MP, Fens N, Brinkman P, et al. Smelling the diagnosis: the electronic nose as a diagnostic tool in inflammatory arthritis. A case-reference study. Plos One. 2016;11:e0151715.