Next Decade Research in Asthma: Broad Omics-Based Exploration Versus Targeted Airway Epithelium Studies

Understanding asthma's endotypes is key to advancing precision medicine. Using omics techniques on sputum, bronchial epithelium, and blood have revealed T2 and non-T2 asthma, each which have been further categorized into T2 and non-T2 subgroups. Despite advances in understanding asthma's molecular complexity, many questions remain. Future research could either enhance current multiomics approaches with sophisticated bioinformatics or integrate hypothesis-driven research. It is now widely accepted that the airway epithelium starts and regulates the inflammatory cascade in asthma. If asthma originates in the altered epithelium, concentrating research on epithelial dysfunction is logical. This approach is likely more straightforward than analyzing the multitude of genes affected by the inflammatory cascade triggered by this disturbed airway epithelium. The airway epithelium comprises various cell types, including basal cells, club cells, ciliated cells, goblet cells, pulmonary neuroendocrine cells, tuft cells, and pulmonary ionocytes, which are connected by junctional complexes including tight junctions, adherens junctions, gap junctions, and desmosomes. The healthy airway epithelium helps support homeostasis, defend against threats, and regulate immunity through innate and adaptive systems. Chronic airway epithelial barrier dysfunction can instigate and propagate excessive immune responses. Knowing the cellular makeup and differentiation of the airway epithelium is vital for creating treatments to restore airway integrity in established asthma. A new consensus highlights focusing research on airway epithelial dysfunction as the main driver of inflammation, marking the start of the "epithelium era" in asthma research.