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Original research
Subtyping emphysematous COPD by respiratory volume change distributions on CT
  1. Hiroshi Shima1,
  2. Naoya Tanabe1,
  3. Akira Oguma2,
  4. Kaoruko Shimizu2,
  5. Shizuo Kaji3,
  6. Kunihiko Terada4,
  7. Tsuyoshi Oguma1,
  8. Takeshi Kubo5,
  9. Masaru Suzuki2,
  10. Hironi Makita2,6,
  11. Atsuyasu Sato1,
  12. Masaharu Nishimura2,6,
  13. Susumu Sato1,
  14. Satoshi Konno2,
  15. Toyohiro Hirai1
  1. 1 Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  2. 2 Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan
  3. 3 Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan
  4. 4 Terada Clinic, Respiratory Medicine and General Practice, Himeji, Japan
  5. 5 Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  6. 6 Hokkaido Medical Research Institute for Respiratory Diseases, Sapporo, Japan
  1. Correspondence to Dr Naoya Tanabe, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; ntana{at}


Background There is considerable heterogeneity among patients with emphysematous chronic obstructive pulmonary disease (COPD). We hypothesised that in addition to emphysema severity, ventilation distribution in emphysematous regions would be associated with clinical-physiological impairments in these patients.

Objective To evaluate whether the discordance between respiratory volume change distributions (from expiration to inspiration) in emphysematous and non-emphysematous regions affects COPD outcomes using two cohorts.

Methods Emphysema was quantified using a low attenuation volume percentage on inspiratory CT (iLAV%). Local respiratory volume changes were calculated using non-rigidly registered expiratory/inspiratory CT. The Ventilation Discordance Index (VDI) represented the log-transformed Wasserstein distance quantifying discordance between respiratory volume change distributions in emphysematous and non-emphysematous regions.

Results Patients with COPD in the first cohort (n=221) were classified into minimal emphysema (iLAV% <10%; n=113) and established emphysema with high VDI and low VDI groups (n=46 and 62, respectively). Forced expiratory volume in 1 s (FEV1) was lower in the low VDI group than in the other groups, with no difference between the high VDI and minimal emphysema groups. Higher iLAV%, more severe airway disease and hyperventilated emphysematous regions in the upper-middle lobes were independently associated with lower VDI. The second cohort analyses (n=93) confirmed these findings and showed greater annual FEV1 decline and higher mortality in the low VDI group than in the high VDI group independent of iLAV% and airway disease on CT.

Conclusion Lower VDI is associated with severe airflow limitation and higher mortality independent of emphysema severity and airway morphological changes in patients with emphysematous COPD.

  • Emphysema
  • Imaging/CT MRI etc
  • COPD Pathology
  • Lung Physiology

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors HS: Concept and design of the study, data acquisition, statistical analysis, data interpretation and drafting of the manuscript; NT: concept and design of the study, data acquisition, data interpretation, manuscript editing, the guarantor of the paper; AO: analyses of CT data and data interpretation; KS: data interpretation; SK: data interpretation; KT: data acquisition and interpretation; TO: data interpretation and creating software to analyse the airway structure; TK: data interpretation; MS: data interpretation; HM: data acquisition and interpretation; AS: data acquisition and interpretation; MN: data acquisition, data interpretation, and critical revision of the manuscript; SS: data acquisition and interpretation; SK: data interpretation and revision of the manuscript; TH: data interpretation and revision of the manuscript for important intellectual content.

  • Funding The Kyoto-Himeji cohort was partially supported by a grant from the Fujifilm Corporation and Japan Society for the Promotion of Science (JSPS) (Grants-in Aid for scientific research 19K08624). The Hokkaido COPD Cohort Study was supported by a scientific research grant to the Hokkaido COPD Cohort Study from the Ministry of Education, Science, Culture and Sports of Japan (17390239 and 2139053 to MN), Nippon Boehringer Ingelheim, Pfizer, and the Respiratory Failure Research Group received a grant from the Ministry of Health, Labour, and Welfare, Japan for the Hokkaido COPD cohort.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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