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- Brinkman, P, et al.
(författare)
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Exhaled volatile organic compounds as markers for medication use in asthma
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:2
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the 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/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry).MethodsSamples 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 characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation.ResultsData were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p<0.01).ConclusionWe have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring.
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- Pasman, JA, et al.
(författare)
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The CADM2 Gene and Behavior: A Phenome-Wide Scan in UK-Biobank
- 2022
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Ingår i: Behavior genetics. - : Springer Science and Business Media LLC. - 1573-3297 .- 0001-8244. ; 52:4-5, s. 306-314
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Tidskriftsartikel (refereegranskat)abstract
- The cell adhesion molecule 2 (CADM2) gene has appeared among the top associations in a wide range of genome-wide association studies (GWASs). This study aims to: (1) examine how widespread the role of CADM2 is in behavioural traits, and (2) investigate trait-specific effects on CADM2 expression levels across tissues. We conducted a phenome-wide association study in UK Biobank (N = 12,211–453,349) on 242 psycho-behavioral traits, both at the SNP and the gene-level. For comparison, we repeated the analyses for other large (and high LD) genes. We found significant associations between CADM2 and 50 traits (including cognitive, risk taking, and dietary traits), many more than for the comparison genes. We show that many trait associations are reduced when taking geographical stratification into account. S-Predixcan revealed that CADM2 expression in brain tissues was significantly associated with many traits; highly significant effects were also observed for lung, mammary, and adipose tissues. In conclusion, this study shows that the role of CADM2 extends to a wide range of psycho-behavioral traits, suggesting these traits may share a common biological denominator.
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