Mueller SK, Wendler O, Nocera A, et al. - In this prospective study involving 66 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), 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. All study participants had surgery, administration of topical/oral steroids, and outpatient mucus sampling at 10 time-points over 2 years. According to results, 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. Findings suggested 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.