Instability Of Sputum Molecular Phenotypes In U-Biopred Severe Asthma

The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project has described phenotypic differences of severe asthma using a systems biology approach. We obtained three molecular phenotypes termed transcription-associated clusters (TACs) using hierarchical clustering of differentially-expressed transcripts between T2-high and T2-low [1]. TAC1 was characterised by receptors IL33R, CCR3 and TSLPR, with the highest enrichment of gene signatures for IL-13/Type-2 (T2) inflammation with sputum eosinophilia, while TAC2 by inflammasome-associated genes, interferon-α (IFN-α) and tumour necrosis factor-α(TNF-α)-associated genes with sputum neutrophilia and TAC3, by metabolic and mitochondrial function genes with pauci-granulocytic inflammation. Given that sputum eosinophilia may vary with time in many asthmatic subjects [2, 3], we hypothesised that TAC status may also change with time.\n\nFootnotes \n\nThis manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.\n\nConflict of interest: Dr. Z. KERMANI has nothing to disclose.\n\nConflict of interest: Dr. Pavlidis has nothing to disclose.\n\nConflict of interest: Dr. Xie has nothing to disclose.\n\nConflict of interest: Dr. Sun has nothing to disclose.\n\nConflict of interest: Dr. Loza reports other from Janssen RD.\n\nConflict of interest: F. Baribaud reports that he is an employee and share holder of Janssen R\u0026D, Pharmaceutical Companies of Johnson \u0026 Johnson.\n\nConflict of interest: Dr. Fowler reports grants from IMI, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, outside the submitted work;.\n\nConflict of interest: Dr. Shaw reports personal fees from GSK, personal fees from AstraZeneca, personal fees from Teva, personal fees from Boehringer Ingelheim, outside the submitted work;.\n\nConflict of interest: Dr. Fleming reports personal fees from Advisory Board membership, grants for research, personal fees from payments for lectures, outside the submitted work.\n\nConflict of interest: Dr. Howarth reports Part time employment by GSK as Global Medical Expert.\n\nConflict of interest: Dr. Sousa has nothing to disclose.\n\nConflict of interest: Miss Corfield has nothing to disclose.\n\nConflict of interest: Dr. AUFFRAY has nothing to disclose.\n\nConflict of interest: Dr. De Muelder has nothing to disclose.\n\nConflict of interest: Dr. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study;.\n\nConflict of interest: Dr. Guo has nothing to disclose.\n\nConflict of interest: Dr. Uddin reports he is an employee of AstraZeneca and holds shares in the company.\n\nConflict of interest: Dr. Djukanovic reports personal fees from TEVA, grants and personal fees from Novartis, and personal fees and other support from Synairgen outside the submitted work.\n\nConflict of interest: Dr. Adcock reports personal fees from Advisory Board membership, grants from Grants, personal fees from Payments for lectures, outside the submitted work;.\n\nConflict of interest: KFC has received honoraria for participating on Advisory Board meetings of GSK, AZ, Novartis, Merck, BI , Roche and TEVA regarding treatments for asthma and chronic obstructive pulmonary disease and on the Scientific Advisory Board of the Clean Breathing Institute supported by GSK Health Care Consumer Products. He has also been renumerated for speaking engagements by AZ, Novartis and Merck.