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Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma

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Title: Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma
Authors: Konno, Satoshi Browse this author →KAKEN DB
Taniguchi, Natsuko Browse this author
Makita, Hironi Browse this author →KAKEN DB
Nakamaru, Yuji Browse this author →KAKEN DB
Shimizu, Kaoruko Browse this author →KAKEN DB
Shijubo, Noriharu Browse this author
Fuke, Satoshi Browse this author
Takeyabu, Kimihiro Browse this author
Oguri, Mitsuru Browse this author
Kimura, Hirokazu Browse this author
Maeda, Yukiko Browse this author
Suzuki, Masaru Browse this author →KAKEN DB
Nagai, Katsura Browse this author →KAKEN DB
Ito, Yoichi M. Browse this author →KAKEN DB
Wenzel, Sally E. Browse this author
Nishimura, Masaharu Browse this author →KAKEN DB
Keywords: severe asthma
cluster analysis
Issue Date: Jan-2018
Publisher: American Thoracic Society
Journal Title: Annals of the American Thoracic Society
Volume: 15
Issue: 1
Start Page: 33
End Page: 41
Publisher DOI: 10.1513/AnnalsATS.201701-065OC
PMID: 28910142
Abstract: Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Results: Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. Conclusions: This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.
Rights: Originally Published in: Satoshi Konno, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M. Ito, Sally E. Wenzel, and Masaharu Nishimura, for the HiCARAT Investigators. Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma. Annals of the American Thoracic Society, 2018;Vol 15, No 1:pp 33–41. DOI:10.1513/AnnalsATS.201701-065OC Copyright © 2018 by the American Thoracic Society The final publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 今野 哲

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