BibTex format
@article{Kermani:2024:10.1183/13993003.00207-2024,
author = {Kermani, NZ and Chung, KF and Macis, G and Santini, G and Clemeno, FAA and Versi, A and Sun, K and Abdel-Aziz, MI and Andersson, LI and Auffray, C and Badi, Y and Bakke, P and Brightling, C and Brinkman, P and Caruso, M and Chanez, P and De, Meulder B and Djukanovic, R and Fabbri, L and Fowler, SJ and Horvath, I and Howarth, P and James, AJ and Kolmert, J and Kraft, M and Li, C-X and Maitland-van, der Zee AH and Malerba, M and Papi, A and Rabe, K and Sanak, M and Shaw, DE and Singh, D and Sparreman, Mikus M and van, Den Berge M and Wheelock, AM and Wheelock, CE and Yasinska, V and Guo, Y and Wagers, S and Barnes, PJ and Bush, A and Sterk, PJ and Dahlen, S-E and Adcock, IM and Siddiqui, S and Montuschi, P},
doi = {10.1183/13993003.00207-2024},
journal = {European Respiratory Journal},
title = {Radiomultiomics: quantitative CT clusters of severe asthma associated with multi-omics},
url = {http://dx.doi.org/10.1183/13993003.00207-2024},
volume = {64},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - RationaleLung quantitative computed tomographic (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways.MethodsWe used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort. The same qCT measurements were used to replicate qCT clusters in a subsample of the ATLANTIS asthma cohort (n=97). We performed integrated enrichment analysis using blood, sputum, bronchial biopsies, bronchial brushings and nasal brushings transcriptomics and blood and sputum proteomics to characterize radiomultiomic-associated clusters (RACs).ResultsqCT clusters and clinical features in U-BIOPRED were replicated in the matched ATLANTIS cohort. In the U-BIOPRED cohort, RAC1 (n=30) was predominantly female with elevated BMI, mild airflow limitation, normal qCT parameters and upregulation of the complement pathway. RAC2 (n=34) subjects had a lower degree of airflow limitation, airway wall thickness and dilatation, with upregulation of proliferative pathways, including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B (NTRK2/TRKB), and down-regulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signaling and signaling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9.ConclusionsU-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent anovel strategy to identify new molecular pathways in asthma pathobiology.
AU - Kermani,NZ
AU - Chung,KF
AU - Macis,G
AU - Santini,G
AU - Clemeno,FAA
AU - Versi,A
AU - Sun,K
AU - Abdel-Aziz,MI
AU - Andersson,LI
AU - Auffray,C
AU - Badi,Y
AU - Bakke,P
AU - Brightling,C
AU - Brinkman,P
AU - Caruso,M
AU - Chanez,P
AU - De,Meulder B
AU - Djukanovic,R
AU - Fabbri,L
AU - Fowler,SJ
AU - Horvath,I
AU - Howarth,P
AU - James,AJ
AU - Kolmert,J
AU - Kraft,M
AU - Li,C-X
AU - Maitland-van,der Zee AH
AU - Malerba,M
AU - Papi,A
AU - Rabe,K
AU - Sanak,M
AU - Shaw,DE
AU - Singh,D
AU - Sparreman,Mikus M
AU - van,Den Berge M
AU - Wheelock,AM
AU - Wheelock,CE
AU - Yasinska,V
AU - Guo,Y
AU - Wagers,S
AU - Barnes,PJ
AU - Bush,A
AU - Sterk,PJ
AU - Dahlen,S-E
AU - Adcock,IM
AU - Siddiqui,S
AU - Montuschi,P
DO - 10.1183/13993003.00207-2024
PY - 2024///
SN - 0903-1936
TI - Radiomultiomics: quantitative CT clusters of severe asthma associated with multi-omics
T2 - European Respiratory Journal
UR - http://dx.doi.org/10.1183/13993003.00207-2024
UR - https://publications.ersnet.org/content/erj/early/2024/08/01/1399300300207-2024
VL - 64
ER -