Abstract
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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Brinkman has nothing to disclose.
Conflict of interest: Dr. Ahmed has nothing to disclose.
Conflict of interest: Dr. Gómez has nothing to disclose.
Conflict of interest: Dr. Knobel reports In addition, Dr. Knobel has a patent Inline drying of breath sample pending.
Conflict of interest: Dr. Weda has nothing to disclose.
Conflict of interest: Dr. Vink has nothing to disclose.
Conflict of interest: Dr. Nijsen has nothing to disclose.
Conflict of interest: Dr. Wheelock has nothing to disclose.
Conflict of interest: Dr. Dahlén reports other from AZ, GSK, Merck, Novartis, Sanofi, Teva, outside the submitted work.
Conflict of interest: Dr. Montuschi has nothing to disclose.
Conflict of interest: Dr. Richard Knowles reports personal fees from Knowles Consulting Ltd, outside the submitted work.
Conflict of interest: Dr. Vijverberg has nothing to disclose.
Conflict of interest: Dr. Maitland-van der Zee reports grants from Boehringer Ingelheim, personal fees from Astra Zeneca, and Chiesi outside the submitted work.
Conflict of interest: Dr. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study; other from Scientific Advisor and 4% interest in Breathomix BV, outside the submitted work.
Conflict of interest: Dr. Fowler reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Chiesi, outside the submitted work.
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