Pathophysiology

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition of the nasal mucosa and paranasal sinuses that affects an estimated 1% of the US population.^1,2 It is a subset of chronic rhinosinusitis that occurs in 20%-30% of people with the disease.² Patients are usually diagnosed between 40 and 60 years of age, with an average age of onset of 42 years.³ CRSwNP is found more commonly in males than females, though females with CRSwNP may have more severe disease.²

CRSwNP is characterized by airway epithelial cell dysfunction, including impaired barrier function and mucociliary clearance.⁴ It is associated with both local inflammation of the nasal passages and systemic airway inflammation.² The biological mechanisms leading to nasal polyps in CRSwNP are poorly understood.⁴ In addition, higher levels of Staphylococcus aureus colonization of the upper airway have been observed in patients with CRSwNP.² This can contribute to persistent disease through biofilm formation, immune dysregulation, inflammation, and barrier dysfunction.²

Type 2 inflammation has been reported in 85% of patients with CRSwNP, including those with the highest disease burden.^2,4 The type 2 inflammatory pathway begins when antigen-presenting cells activate Th2 cells, releasing Th2 cytokines. including IL-4, IL-13, and IL-5.⁵ These Th2 cytokines recruit mast cells, eosinophils, basophils, goblet cells, M2 macrophages, and B cells, and they are the drivers of many of the inflammatory tissue responses observed in CRSwNP.⁵