Association between exhaled volatile organic compounds and urinary levels of oral corticosteroids within the U-BIOPRED Cohort

Rationale: In uncontrolled asthma short courses of oral corticosteroids (OCS) are often prescribed, however it is difficult to monitor their uptake. Since our lungs are in direct contact with blood, the analysis of exhaled volatile organic compounds (VOCs) may be suitable for monitoring the uptake and distribution of OCS. Objective: To test the association between exhaled VOCs by gas chromatography-mass spectrometry (GC-MS) and urinary levels of prednisolone and its metabolites in severe asthma patients. Methods: In this pan-European study, urine and breath samples were collected from adult severe asthma patients. Analysis of urine samples was done by liquid chromatography-mass spectrometry (LC-MS). VOCs were trapped on Tenax tubes and analyzed by GC-MS. Statistical analysis was based on: 1) univariate Wilcoxon sum-rank testing (p<0.05) plus computation of area under the receiver operating characteristics curve (AUC>0.7) [yes vs. no urinary prednisolone detected], 2) multivariate sparse partial least squares (SLPS) modeling and 3) bootstrapped linear regression. Results: Complete data were available for 108 patients [mean (± SD) age 52 (±14) years, 48% male, 68% using daily OCSs]. Ten VOCs endured univariate testing, of which four [identification in progress] were combined in the SPLS model. Regression analysis between the multivariate model and urinary prednisolone levels resulted in a R2 of 0.63 (95%CI: 0.33-0.94), p<0.01. Conclusion: This study revealed an exhaled VOC profile potentially associated with urinary prednisolone levels, suggesting that breathomics qualifies for development into a point of care tool for therapeutic drug monitoring.