Mueller SK, Wendler O, Nocera A, et al. - Researchers ascertained if prospective sampling of these mucus proteins (cystatin 2 (CST2), pappalysin-A (PAPP-A), periostin, serpinE1, and serpinF2) could anticipate medical failure and the need for revision surgery in this prospective study including 66 individuals with chronic rhinosinusitis with nasal polyps (CRSwNP). All participants in the study had surgery, administration of topical/oral steroids, and outpatient mucus sampling at 10 time-points over 2 years. The authors discovered that all patients showed a significant drop in CST2, PAPP-A, and periostin after their initial surgery. Despite steroids, the recalcitrant group showed escalations in all proteins, with concentrations at 1 year greater than those of the stable group. They recommended that early recurrences and medical recalcitrance in CRSwNP can be noninvasively predicted by serial, prospective sampling of mucus CST2, PAPP-A, and periostin levels. These biosignatures can help predict the course of the disease and the need for revision surgery as well as help guide individualized therapy.