Induced sputumeosinophilia has also been used as a biomarker in clinical trials and has proven informative for regulating corticosteroid dose for asthma control. More recently, an assay based on three IL-13 regulated genes showed promise in distinguishing Th2 driven asthma from BMS-907351 alternate mechanisms . Molecular indicators from airway samples for Th2-low asthmatics have remained elusive. Our results indicate the possibility that airway hyperresponsiveness in these endotypes is elicited by triggers due to a heightened state of alert for circulating innate immune cells. Detection of increased airway inflammation will consequently be restricted to periods of active airway constriction Regorafenib during an asthma attack, highlighting the importance of systemic biomarkers for asthma diagnosis. Given that inhaled corticosteroids are most effective in Th2-high individuals, our putative endotypes from the right hand side of the decision tree provide important information for development of new therapies and diagnostic biomarkers for this ever-growing population. Specifically, our results suggest that a biomarker panel including markers of systemic inflammation as well as metabolic syndrome is needed for better diagnosis of distinct asthma endotypes. The strong association between our asthma endotypes and both systemic inflammation and metabolic syndrome-associated clinical indicators suggests that asthma incidence for the Th2- low endotypes described here may continue to rise with the worldwide escalation in obesity. Given that inhaled corticosteroids are most effective in Th2-high individuals, our putative Th2-low endotypes add important mechanistic information for development of new therapies and diagnostic biomarkers for this ever-growing population. These proposed endotypes, along with their associations with key biological pathways, should also provide valuable insights for interpreting the continually expanding list of genes putatively identified as genetic risk factors for asthma. Finally, a better understanding of the various asthma endotypes from this and complementary studies provides a scientifically defensible foundation for the evaluation of the many environmental factors influencing each mechanistically distinct endotype. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels that have improved sensitivity and specificity in clinical diagnosis of asthma over biomarkers currently available and reflected in conventional studies of asthmatics.