For a study, researchers sought to discover the underlying molecular pathways of type 2–low chronic rhinosinusitis (CRS) with the hope of improving tailored therapy by stratifying patients. Proteins in nasal secretions and tissues of CRS patients were analyzed using Luminex assays. In nasal tissue, immunostainings were used to look for changes in neutrophils, granulocyte-colony stimulating factor (G-CSF), and its receptor. G-CSF was used to activate neutrophils obtained from healthy participants’ blood. Flow cytometry was used to examine the effects on apoptosis and neutrophil activity. In type 2–low CRS patients, G-CSF levels were considerably higher in nasal tissue and secretory fluid than in type 2–high CRS patients. A substantial infiltration of neutrophils expressing both G-CSF and its receptor was found in the nasal polyp tissue of type 2–low individuals, suggesting a neutrophil-intrinsic autocrine survival mechanism. Neutrophils were stimulated and resistant to apoptosis in response to G-CSF, possibly contributing to persistent inflammation. Patients with type 2–high nasal polyps treated with IgE-blocking omalizumab had higher G-CSF concentrations than those who were not. G-CSF was a cytokine that regulated neutrophils in type 2–low CRS and could be used to diagnose and treat the condition.