Relationships of computed tomography-based small vessel indices of the lungs with ventilation heterogeneity and high transfer coefficients in non-smokers with asthma

Kaoruko Shimizu; Hirokazu Kimura; Naoya Tanabe; Shotaro Chubachi; Susumu Sato; Masaru Suzuki; Kazuya Tanimura; Hiroaki Iijima; Akira Oguma; Yoichi M Ito; Nobuyasu Wakazono; Michiko Takimoto-Sato; Machiko Matsumoto-Sasaki; Yuki Abe; Nozomu Takei; Hironi Makita; Masaharu Nishimura; Satoshi Konno; Hi-CARAT investigators

doi:10.3389/fphys.2023.1137603

Relationships of computed tomography-based small vessel indices of the lungs with ventilation heterogeneity and high transfer coefficients in non-smokers with asthma

Front Physiol. 2023 Mar 1:14:1137603. doi: 10.3389/fphys.2023.1137603. eCollection 2023.

Authors

Kaoruko Shimizu¹, Hirokazu Kimura¹, Naoya Tanabe², Shotaro Chubachi³, Susumu Sato², Masaru Suzuki¹, Kazuya Tanimura⁴, Hiroaki Iijima⁵, Akira Oguma¹, Yoichi M Ito⁶, Nobuyasu Wakazono¹, Michiko Takimoto-Sato¹, Machiko Matsumoto-Sasaki¹, Yuki Abe¹, Nozomu Takei¹, Hironi Makita^{1

7}, Masaharu Nishimura^{1

7}, Satoshi Konno¹; Hi-CARAT investigators

Affiliations

¹ Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
² Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Department of Medicine, Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan.
⁴ Department of Respiratory Medicine, Nara Medical University, Kashihara, Japan.
⁵ Department of Respiratory Medicine, Tsukuba Medical Center Hospital, Tsukuba, Japan.
⁶ Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan.
⁷ Hokkaido Medical Research Institute for Respiratory Diseases, Sapporo, Japan.

Abstract

Background: The mechanism of high transfer coefficients of the lungs for carbon monoxide (Kco) in non-smokers with asthma is explained by the redistribution of blood flow to the area with preserved ventilation, to match the ventilation perfusion. Objectives: To examine whether ventilation heterogeneity, assessed by pulmonary function tests, is associated with computed tomography (CT)-based vascular indices and Kco in patients with asthma. Methods: Participants were enrolled from the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) study that included a prospective asthmatic cohort. Pulmonary function tests including Kco, using single breath methods; total lung capacity (TLC), using multiple breath methods; and CT, were performed on the same day. The ratio of the lung volume assessed using single breath methods (alveolar volume; V_A) to that using multiple breath methods (TLC) was calculated as an index of ventilation heterogeneity. The volume of the pulmonary small vessels <5 mm² in the whole lung (BV5 volume), and number of BV5 at a theoretical surface area of the lungs from the plural surface (BV5 number) were evaluated using chest CT images. Results: The low V_A/TLC group (the lowest quartile) had significantly lower BV5 number, BV5 volume, higher BV5 volume/BV5 number, and higher Kco compared to the high V_A/TLC group (the highest quartile) in 117 non-smokers, but not in 67 smokers. Multivariable analysis showed that low V_A/TLC was associated with low BV5 number, after adjusting for age, sex, weight, lung volume on CT, and CT emphysema index in non-smokers (not in smokers). Conclusion: Ventilation heterogeneity may be associated with low BV5 number and high Kco in non-smokers (not in smokers). Future studies need to determine the dynamic regional system in ventilation, perfusion, and diffusion in asthma.

Keywords: Kco; asthma; computed tomography; pulmonary small vessels; ventilation heterogeneity.

Copyright © 2023 Shimizu, Kimura, Tanabe, Chubachi, Sato, Suzuki, Tanimura, Iijima, Oguma, Ito, Wakazono, Takimoto-Sato, Matsumoto-Sasaki, Abe, Takei, Makita, Nishimura, Konno and Hi-CARAT investigators.

Grants and funding

The Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) Study is supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (24249049 to MN, 26461151 to SK) and a research grant from the Japan Allergy Foundation, AstraZeneca, and Kyorin.