Exhaled volatile organic compounds for phenotyping chronic obstructive pulmonary disease: a cross-sectional study

Abstract

BackgroundNon-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future. Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes. We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease (COPD) and clinically relevant disease phenotypes.MethodsBreath samples from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry. Subjects with COPD also underwent sputum induction. Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis: 1. principal component analysis; 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis.ResultsComparing COPD versus healthy controls, principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71% of the variance. Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69%. The model had 85% sensitivity, 50% specificity and ROC area under the curve of 0.74. Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy. Models were constructed which classified subjects with ≥2% sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95. Potential biomarkers correlated to clinical variables were identified in each subgroup.ConclusionThe exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinically relevant COPD subgroups. If these findings are validated in prospective cohorts, they may have diagnostic and management value in this disease.

The scent of human diseases: a review on specific volatile organic compounds as diagnostic biomarkers

“…Basanta et al . identified a total of 487 VOCs from 71 human subjects, 39 of whom were COPD‐patients and 32 healthy controls.…”

Laser spectroscopy for breath analysis: towards clinical implementation

“…Several methods are currently employed for exhaled volatiles detection, among which mass spectrometry (e.g., gas chromatography mass spectrometry, GC-MS) is the most widely used analytical tool [11][12][13][14]. However, the GC-MSbased instruments are limited to laboratory settings, do not allow online sampling (i.e., exhaling directly into the instrument, usually using an inbuilt system or an external breath sampler for feedback exhaled airflow control, including a flowmeter) and have a relatively long analysis time (in the order of tens of minutes).…”

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