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@article{Reinke:2022:10.1183/13993003.01733-2021,
author = {Reinke, SN and Naz, S and Chaleckis, R and Gallart-Ayala, H and Kolmert, J and Kermani, NZ and Tiotiu, A and Broadhurst, D and Lundqvist, A and Olsson, H and Strom, M and Wheelock, AM and Gomez, C and Ericsson, M and Sousa, AR and Riley, JH and Bates, S and Scholfield, J and Loza, M and Baribaud, F and Bakke, PS and Caruso, M and Chanez, P and Fowler, SJ and Geiser, T and Howarth, P and Horvath, I and Krug, N and Montuschi, P and Behndig, A and Singer, F and Musial, J and Shaw, DE and Dahlen, B and Hu, S and Lasky-Su, J and Sterk, PJ and Chung, KF and Djukanovic, R and Dahlen, S-E and Adcock, IM and Wheelock, CE},
doi = {10.1183/13993003.01733-2021},
journal = {European Respiratory Journal},
pages = {1--17},
title = {Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study},
url = {http://dx.doi.org/10.1183/13993003.01733-2021},
volume = {59},
year = {2022}
}

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TY  - JOUR
AB  - Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-speci
AU  - Reinke,SN
AU  - Naz,S
AU  - Chaleckis,R
AU  - Gallart-Ayala,H
AU  - Kolmert,J
AU  - Kermani,NZ
AU  - Tiotiu,A
AU  - Broadhurst,D
AU  - Lundqvist,A
AU  - Olsson,H
AU  - Strom,M
AU  - Wheelock,AM
AU  - Gomez,C
AU  - Ericsson,M
AU  - Sousa,AR
AU  - Riley,JH
AU  - Bates,S
AU  - Scholfield,J
AU  - Loza,M
AU  - Baribaud,F
AU  - Bakke,PS
AU  - Caruso,M
AU  - Chanez,P
AU  - Fowler,SJ
AU  - Geiser,T
AU  - Howarth,P
AU  - Horvath,I
AU  - Krug,N
AU  - Montuschi,P
AU  - Behndig,A
AU  - Singer,F
AU  - Musial,J
AU  - Shaw,DE
AU  - Dahlen,B
AU  - Hu,S
AU  - Lasky-Su,J
AU  - Sterk,PJ
AU  - Chung,KF
AU  - Djukanovic,R
AU  - Dahlen,S-E
AU  - Adcock,IM
AU  - Wheelock,CE
DO  - 10.1183/13993003.01733-2021
EP  - 17
PY  - 2022///
SN  - 0903-1936
SP  - 1
TI  - Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study
T2  - European Respiratory Journal
UR  - http://dx.doi.org/10.1183/13993003.01733-2021
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000834085100003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://erj.ersjournals.com/content/59/6/2101733
UR  - http://hdl.handle.net/10044/1/101711
VL  - 59
ER  -

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