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; 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.
At 1 year, 45% of severe asthma change molecular phenotype as determined by sputum transcriptomic analysis. Together with concomitant shift in sputum granulocytic markers, this may indicate variability of driving mechanisms in this unstable group. https://bit.ly/35aj489