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Background: Asthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of “TH2-high” asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma. Methods: Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry. Results: The serum concentrations of periostin were significantly higher (P ¼ 0.014) in asthmatics [70.0 (54.0e93.5) ng/ml] than in healthy subjects [57.0 (39.0e63.0) ng/ml], though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize “high-periostin” phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P ¼ 0.04), had a higher prevalence of aspirin intolerance (P ¼ 0.04) or concomitant nasal disorders (P ¼ 0.03e0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P ¼ 0.02e0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the “high-periostin” phenotype. Conclusion: Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.