Exhaled Breath Profiles: Biomarker for Diagnosing COPD Exacerbations

Researchers sought to determine whether exhaled breath profiles as measured by Gas Chromatography-Mass Spectrometry or electronic nose vary between stable disease and exacerbations and can potentially serve as biomarkers for COPD exacerbations.

The use of exhaled breath tests may qualify as a noninvasive biomarker for the diagnosis of an acute exacerbation of chronic obstructive pulmonary disease (COPD). A prospective observational follow-up study on the subject was conducted at 2 teaching hospitals in Amsterdam, The Netherlands, and the results were published in the Journal of Chronic Obstructive Pulmonary Disease.1

Recognizing that the diagnosis of a COPD exacerbation is based solely on symptoms, the investigators hypothesized that exhaled breath profiles as measured by gas chromatography-mass spectrometry (GC-MS) or electronic nose (eNose) differ between patients with stable disease vs patients with disease exacerbations and thus may be potential biomarkers for COPD exacerbations. In the study, researchers obtained breath samples during stable COPD, during a subsequent disease exacerbation, and after recovery. They analyzed the samples using GC-MS and eNose.

The investigators measured clinical control with the use of the Clinical COPD Questionnaire (CCQ) symptom scores,2 which were linked to univariate outcomes of GC-MS and eNose via the use of analysis of covariance. The CCQ is a self-administered questionnaire that includes 10 questions in 3 domains (ie, symptoms, functional state, and mental state). After multivariate analysis modeling by Principal Component Analysis, the investigators conducted paired student t-tests.

The researchers told all patients to refrain from eating, drinking, and smoking for ≥2 hours before the collection of breath samples to minimize the influence of exogenous compounds. They included a total of 68 patients in the study; 31 experienced an exacerbation and 18 of these fulfilled the predefined criteria. Researchers successfully obtained breath samples from 18 patients during an exacerbation and from 16 patients after recovery. Overall, 14 patients had complete data available for GC-MS analysis and 14 had complete data for eNose analysis; 12 of these patients had complete data for both analyses.

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Results of the study demonstrated significant differences in breathprints obtained during exacerbations compared with baseline and recovery for both GC-MS and eNose. Breath profiles obtained by GC-MS and eNose demonstrated correct classification of 71% of patients (10/14) at baseline vs exacerbation and of 78% of patients (11/14) for exacerbation vs recovery.

The investigators concluded that these findings offer proof of principle that exhaled breath can serve as a noninvasive biomarker for diagnosing COPD exacerbations. Of particular note is the fact that as breathprints at baseline and after clinical recovery did not differ, this suggests the existence of complete recovery of metabolic activity as captured in exhaled air. Replication of the current data in a large COPD cohort is warranted to render the analysis of volatile organic compounds applicable to the monitoring of patients with COPD.


1. van Velzen P, Brinkman P, Knobel HH, et al. Exhaled breath profiles before, during and after exacerbation of COPD: a prospective follow-up study [published online October 7, 2019]. COPD.  doi:10.1080/15412555.2019.1669550

2. van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire.Health Qual Life Outcomes. 2003;1:13.