Linking endotypes to omics profiles in difficult-to-control asthma using the diagnostic Chinese medicine syndrome differentiation algorithm

AbstractObjective: Patients with difficult-to-control asthma have difficulty breathing almost all of the time, even leading to life-threatening asthma attacks. However, only few diagnostic markers for this disease have been identified. We aimed to take advantage of unique Chinese medicine theories for phenotypic classification and to explore molecular signatures in difficult-to-control asthma. Methods: The Chinese medicine syndrome differentiation algorithm (CMSDA) is a syndrome-scoring classification method based on the Chinese medicine overall observation theory. Patients with difficult-to-control asthma were classified into Cold- and Hot-pattern groups according to the CMSDA. DNA methylation and metabolomic profiles were obtained using Infinium Human Methylation 450 BeadChip and gas chromatography-mass spectrometer. Subsequently, an integrated bioinformatics analysis was performed to compare those two patterns and identify Cold/Hot-associated candidates, followed by functional validation studies. Resul...