Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma

Houman Goudarzi, Hirokazu Kimura, Hiroki Kimura, Hironi Makita, Michiko Takimoto-Sato, Yuki Abe, Akira Oguma, Munehiro Matsumoto, Nozomu Takei, Machiko Matsumoto-Sasaki, Kaoruko Shimizu, Masaru Suzuki, Noriharu Shijubo, Shau ku Huang, Nobuyuki Hizawa, Masaharu Nishimura, Satoshi Konno

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: There are knowledge gaps in the potential role of Club cell 16-kDa secretory protein (CC16) in severe asthma phenotypes and type 2 inflammation, as well as the longitudinal effect of CC16 on pulmonary function tests and exacerbation risk in epidemiological studies. Objective and methods: To assess whether serum CC16 is associated with eosinophilic inflammation in patients with severe asthma. We also examined the effect of this protein on the annual decline in forced expiratory volume in the first second (FEV1) and the risk of exacerbation using a longitudinal approach. We recruited 127 patients with severe asthma from 30 hospitals/pulmonary clinics in Hokkaido, Japan. The least square means and standard error were calculated for T-helper 2 (Th2) biomarkers and pulmonary function test across CC16 tertiles at baseline. We did the same for asthma exacerbation and annual decline in FEV1 with 3 and 5 years’ follow-up, respectively. Results: We found that serum CC16 was inversely associated with sputum eosinophils and blood periostin in a dose-response manner. Baseline CC16 and FEV1/forced vital capacity ratio were positively associated in adjusted models (p for trend = 0.008). Patients with the lowest tertile of serum CC16 levels at baseline had a −14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up (p for trend = 0.031, fully adjusted model). We did not find any association of CC16 with exacerbation risk. Conclusion: Patients with severe asthma with lower circulatory CC16 had enhanced eosinophilic inflammation with rapid FEV1 decline over time.

Original languageEnglish (US)
Article number107089
JournalRespiratory Medicine
StatePublished - Jan 2023


  • CC16
  • Eosinophilic inflammation
  • Periostin
  • Respiratory function
  • Severe asthma
  • Sputum eosinophils
  • T-helper 2 biomarkers

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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