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

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          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 mm 2 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.

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          Most cited references45

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          Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society.

          C. Irvin, A’s Society, SJ Szefler … (2000)
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            ERS/ATS technical standard on interpretive strategies for routine lung function tests

            Sanja Stanojevic, David A Kaminsky, Martin A. Miller … (2021)
            Background Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiologic determinants of test results into functional classifications, and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standard for PFT interpretation. Methods This technical standards document was developed by an international joint task force, appointed by the European Respiratory Society and the American Thoracic Society with multidisciplinary expertise in conducting and interpreting pulmonary function tests, and developing international standards. A comprehensive literature review was conducted, and published evidence was reviewed. Results Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results, respectively are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments. Conclusions PFTs interpretation must be complemented with clinical expertise and consider the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.
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              Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes

              Helen Reddel, Leonard Bacharier, Eric D Bateman … (2021)
              The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β 2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS–formoterol reduces severe exacerbations by ⩾60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS–formoterol as the reliever at all steps: as needed only in Steps 1–2 (mild asthma), and with daily maintenance ICS–formoterol (maintenance-and-reliever therapy, “MART”) in Steps 3–5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS–long-acting β 2-agonist (Steps 3–5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6–11 years, new treatment options are added at Steps 3–4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Physiol
                Journal ID (iso-abbrev): Front Physiol
                Journal ID (publisher-id): Front. Physiol.
                Title: Frontiers in Physiology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-042X
                Publication date (Electronic): 01 March 2023
                Publication date Collection: 2023
                Volume: 14
                Electronic Location Identifier: 1137603
                Affiliations
                [1] 1 Department of Respiratory Medicine , Faculty of Medicine , Hokkaido University , Sapporo, Japan
                [2] 2 Department of Respiratory Medicine , Graduate School of Medicine , Kyoto University , Kyoto, Japan
                [3] 3 Department of Medicine , Division of Pulmonary Medicine , Keio University School of Medicine , Tokyo, Japan
                [4] 4 Department of Respiratory Medicine , Nara Medical University , Kashihara, Japan
                [5] 5 Department of Respiratory Medicine , Tsukuba Medical Center Hospital , Tsukuba, Japan
                [6] 6 Data Science Center , Promotion Unit , Institute of Health Science Innovation for Medical Care , Hokkaido University Hospital , Sapporo, Japan
                [7] 7 Hokkaido Medical Research Institute for Respiratory Diseases , Sapporo, Japan
                Author notes

                Edited by: Lars Knudsen, Hannover Medical School, Germany

                Reviewed by: Sanghun Choi, Kyungpook National University, Republic of Korea

                Haribalan Kumar, The University of Auckland, New Zealand

                *Correspondence: Kaoruko Shimizu, okaoru@ 123456med.hokudai.ac.jp

                This article was submitted to Respiratory Physiology and Pathophysiology, a section of the journal Frontiers in Physiology

                Article
                Publisher ID: 1137603
                DOI: 10.3389/fphys.2023.1137603
                PMC ID: 10014854
                PubMed ID: 36935740
                SO-VID: e5c2cddf-0908-45a7-9c6b-4b3f47eea85e
                Copyright © 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.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 04 January 2023
                Date accepted : 17 February 2023
                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.
                Categories
                Subject: Physiology
                Subject: Original Research

                ScienceOpen disciplines: Anatomy & Physiology
                Keywords: asthma,computed tomography,pulmonary small vessels,ventilation heterogeneity,kco
                Data availability:
                ScienceOpen disciplines: Anatomy & Physiology
                Keywords: asthma, computed tomography, pulmonary small vessels, ventilation heterogeneity, kco

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