Chronic rhinosinusitis with nasal polyps: insights into mechanisms of disease from emerging biological therapies.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disease of the upper airway, with long-term morbidity. With detailed mechanistic studies currently lacking, understanding of the immunopathogenesis is still limited. However, outcomes from CRSwNP clinical studies using biologics that block key mediators or cells may provide some insights into how immune signaling pathways potentially integrate and modulate each other and contribute to disease. Current treatments are often ineffective and there is an urgent unmet clinical need for effective therapeutic strategies. Emerging biologics hold promise. Areas covered: This review covers the biology of CRSwNP in terms of the clinical outcomes reported from blocking immune cascades with available biologics. Immune amplification mechanisms and how biologics can potentially modulate such 'master' cytokines and signaling proteins that drive inflammation and contribute to tissue remodeling in CRSwNP are discussed. Expert commentary: Biologics have the potential to transform CRSwNP treatment. The ability to predict clinical response in a complex disease as CRSwNP to a biologic cannot necessarily be predicted by measuring a single protein or cell as a biomarker of disease. Further studies with biologics must be carefully undertaken to fully evaluate wider biomarker associated pheno-endotype responses along with any associated asthma outcome measures.