TY - JOUR
T1 - Radiomultiomics
T2 - quantitative CT clusters of severe asthma associated with multiomics
AU - Kermani, Nazanin Zounemat
AU - Chung, Kian Fan
AU - Macis, Giuseppe
AU - Santini, Giuseppe
AU - Clemeno, Franz A.A.
AU - Versi, Ali
AU - Sun, Kai
AU - Abdel-Aziz, Mahmoud I.
AU - Andersson, Lars I.
AU - Auffray, Charles
AU - Badi, Yusef
AU - Bakke, Per
AU - Brightling, Chris
AU - Brinkman, Paul
AU - Caruso, Massimo
AU - Chanez, Pascal
AU - De Meulder, Bertrand
AU - Djukanovic, Ratko
AU - Fabbri, Leonardo
AU - Fowler, Stephen J.
AU - Horvath, Ildiko
AU - Howarth, Peter
AU - James, Anna J.
AU - Kolmert, Johan
AU - Kraft, Monica
AU - Li, Chuan Xing
AU - Maitland-Van der Zee, Anke H.
AU - Malerba, Mario
AU - Papi, Alberto
AU - Rabe, Klaus
AU - Sanak, Marek
AU - Shaw, Dominick E.
AU - Singh, Dave
AU - Mikus, Maria Sparreman
AU - van Den Berge, Maarten
AU - Wheelock, Asa M.
AU - Wheelock, Craig E.
AU - Yasinska, Valentyna
AU - Guo, Yi Ke
AU - Wagers, Scott
AU - Barnes, Peter J.
AU - Bush, Andrew
AU - Sterk, Peter J.
AU - Dahlen, Sven Erik
AU - Adcock, Ian M.
AU - Siddiqui, Salman
AU - Montuschi, Paolo
N1 - Publisher Copyright:
Copyright ©The authors 2024.
PY - 2024
Y1 - 2024
N2 - Background Lung quantitative computed tomography (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, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence. Methods We 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 characterise radiomultiomic-associated clusters (RACs). Results qCT 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 body mass index, mild airflow limitation, decreased CT lung volume and increased lung density and upregulation of the complement pathway. RAC2 (n=34) subjects had airway wall thickness and a mild degree of airflow limitation, with upregulation of proliferative pathways including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B, and downregulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signalling and signalling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9. Conclusions U-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent a novel strategy to identify new molecular pathways in asthma pathobiology.
AB - Background Lung quantitative computed tomography (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, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence. Methods We 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 characterise radiomultiomic-associated clusters (RACs). Results qCT 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 body mass index, mild airflow limitation, decreased CT lung volume and increased lung density and upregulation of the complement pathway. RAC2 (n=34) subjects had airway wall thickness and a mild degree of airflow limitation, with upregulation of proliferative pathways including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B, and downregulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signalling and signalling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9. Conclusions U-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent a novel strategy to identify new molecular pathways in asthma pathobiology.
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U2 - 10.1183/13993003.00207-2024
DO - 10.1183/13993003.00207-2024
M3 - Article
C2 - 39401856
AN - SCOPUS:85210548779
SN - 0903-1936
VL - 64
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 5
M1 - 2400207
ER -