BACKGROUND: Nasal polyps and comorbid asthma (NPcA) is a common united airway disease and is highly heterogeneous with respect to clinical, physiologic, and pathologic parameters. The clinical phenotypes of NPcA are poorly understood. OBJECTIVE: We sought to explore clinical phenotypes in patients with NPcA. METHODS: Patients first diagnosed with NPcA were recruited from Rhinological Clinics and Respiratory Clinics. We clustered patients with NPcA based on parameters regarding natural courses and demographic characteristics. Patients were also evaluated with respect to clinical, functional, and inflammatory parameters in both upper and lower airways. RESULTS: Clustering of 110 cases resulted in 3 clusters: cluster 1 (n = 16, 14.55%, atopic NPcA) was predominantly atopic patients with child-onset airway symptoms, intermediate disease duration, history of family asthma, better lung function, and less severe asthma; cluster 2 (n = 32, 29.09%, smoking NPcA) was characterized by more smokers, short disease duration, adult-onset airway symptoms, less atopy, nonsteroidal anti-inflammatory drug sensitivity, prior sinus surgery history, eosinophilic airway phenotypes, worse lung function, and severe computed tomography appearance; and cluster 3 (n = 62, 56.36%, older NPcA) consisted mostly of older patients with long disease duration, adult-onset airway symptoms, less atopy, more noneosinophilic airway phenotypes, and prior sinus surgery history. CONCLUSIONS: Patients with NPcA with 3 distinct natural courses had different inflammatory status and disease severity. Determining the natural course of a patient might help clinicians predict the clinical aspects of NPcA and contribute to phenotype-guided management approaches in the future. (C) 2017 American Academy of Allergy, Asthma & Immunology