Exhaled Volatile Organic Compounds as Markers for Medication Use in Asthma

RATIONALE: Asthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes, however it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry, and may be useful for monitoring drug pharmacokinetics and pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography-time-of-flight-mass spectrometry) with urinary levels of salbutamol and oral corticosteroids (OCS) (by liquid chromatography-high resolution mass spectrometry).

METHODS: Samples were collected at baseline and after 12-18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristics (AUROC) calculation. Results were verified through longitudinal replication and independent validation.

RESULTS: Data were available for 78 patients (baseline: n=48; replication: n=30; validation: n=30). Baseline AUROCs (95% CI) were 82.1 (70.4-93.9) for salbutamol and 78.8 (65.8-91.8) for OCS. These outcomes could adequately be replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone, showed statistically significant correlations (p<0.01).

CONCLUSION: In summary, we have linked exhaled VOCs to urinary detection of salbutamol and OCS. This merits further development of breathomics into a point of care tool for therapeutic drug monitoring.