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Ventilation-perfusion inequality in COVID-19 pneumonia

Year: 2021
Type: letter
Abstract: Letter to the EditorVentilation-perfusion inequality in COVID-19 pneumoniaHaopeng Xu, Nayia Petousi, and Peter A. RobbinsHaopeng XuNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, Nayia PetousiNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, and Peter A. RobbinsDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomPublished Online:16 Aug 2021https://doi.org/10.1152/japplphysiol.00388.2021MoreFiguresReferencesRelatedInformationSectionsGRANTSDISCLAIMERSDISCLOSURESAUTHOR CONTRIBUTIONSAUTHOR NOTESPDF (207 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookXLinkedInWeChat TO THE EDITOR: COVID-19 pneumonia is unusual in the severity of the hypoxemia relative to the degree of atelectasis or consolidation observed in the lung (1). To explore this further, Busana et al. (2) recently reported findings for five patients with severe COVID-19 in whom the fraction of nonaerated lung tissue had been quantified by computed tomography. They assumed that the shunt flow fraction was proportional to the nonaerated lung fraction, and sought to identify ventilation-perfusion (V̇/Q̇) distributions for the aerated element of the lung that would generate the observed arterial Pco2 and Po2. They found that a large fraction of the blood flow was probably distributed toward regions with very low V̇/Q̇, and that overall the results were suggestive of high V̇/Q̇ inequality. Although the authors should be congratulated for making such observations on these patients, there are several aspects of the analysis that give rise to concern. The first is that the authors considered that any randomly generated V̇/Q̇ distribution that predicted values for arterial Pco2 and Po2 to within 10% of the observed values was a potential solution. Although this is approximate at best, of greater concern is that the predicted arterial Pco2 and Po2 values did not scatter around the true value, but rather they were all grouped away from the true value in the direction of higher arterial Pco2 and Po2 (Fig. 6). This suggests that the authors' methodology for identifying V̇/Q̇ distributions to describe the patient data was not particularly successful. The second problem is physiological. In the modeling of Busana et al. (2), regions of very low V̇/Q̇ in the lung were required to ensure that the alveolar Po2 was sufficiently low so that it could not fully oxygenate the blood. A corollary is that the alveolar Pn2 has to be relatively high. However, the inspired O2 fraction was high for all patients, and thus the inspired Pn2 has to be some 100 s of mmHg lower than in the low V̇/Q̇ regions. In these extremely poorly ventilated regions where alveolar Pn2 is much higher, it is inconceivable that N2 will not diffuse significantly both into the blood and retrogradely into the airways. This violates an assumption made implicitly in the model of Busana et al. (2) that all N2 exchange occurs via convection. In particular, an equal convective flow of N2 into and out of all alveolar units is used to generate the relationship between the inspired and expired alveolar ventilation, which, in turn, is required for the derivation of the exact form of the alveolar gas equation (see item 2.2 under Computational Model). Although in many cases this approximation is reasonable, it will break down when both diffusion gradients are very high and convective flows (alveolar ventilation) are very low, as is the case here. Busana et al. (2) concluded that "shunt alone cannot completely account for the hypoxemia and a significant V̇/Q̇ abnormality must be present in COVID-19." In contrast, we consider it likely that their starting assumption that the shunt blood flow fraction is proportional to the nonaerated lung fraction is incorrect. Damage to the pulmonary vascular endothelium by SARS-CoV-2 (3, 4) is likely to impair hypoxic pulmonary vasoconstriction and contribute to a shunt fraction significantly greater than otherwise expected. A higher shunt flow fraction then obviates the need for the extreme V̇/Q̇ distributions (and improbable alveolar Pn2 values) postulated by the modeling of Busana et al. (2).GRANTS This work was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Center (BRC). H.X. was supported by a China Scholarship Council (CSC)-Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI) scholarship. N.P. was supported by the NIHR-Research Capability Funding award.DISCLAIMERS The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research, or the Department of Health.DISCLOSURES No conflicts of interest, financial or otherwise, are declared by the authors.AUTHOR CONTRIBUTIONS P.A.R. conceived and designed research; H.X. analyzed data; P.A.R. drafted manuscript; H.X., N.P., and P.A.R. edited and revised manuscript; H.X., N.P., and P.A.R. approved final version of manuscript.AUTHOR NOTESCorrespondence: P. A. Robbins ([email protected]). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationREFERENCES1. Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D . COVID-19 does not lead to a "typical" acute respiratory distress syndrome. Am J Respir Crit Care Med 201: 1299–1300, 2020. doi:10.1164/rccm.202003-0817LE. Crossref | PubMed | Web of Science | Google Scholar2. Busana M, Giosa L, Cressoni M, Gasperetti A, Girolamo Martinelli DL, Sonzogni A, Lorini A, Palumbo L, Romitti MM, Gattarello F, Steinberg S, Herrmann I, Meissner P, Quintel K, Gattinoni ML . The impact of ventilation-perfusion inequality in COVID-19: a computational model. J Appl Physiol (1985) 130: 865–876, 2021. doi:10.1152/japplphysiol.00871.2020. Link | Web of Science | Google Scholar3. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D . Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 383: 120–128, 2020. doi:10.1056/NEJMoa2015432. Crossref | PubMed | Web of Science | Google Scholar4. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H . Endothelial cell infection and endotheliitis in COVID-19. Lancet 395: 1417–1418, 2020. doi:10.1016/S0140-6736(20)30937-5. Crossref | PubMed | Web of Science | Google Scholar CollectionsAPS Cross-Journal CollectionsCoronavirus-Related Papers Related ArticlesThe impact of ventilation–perfusion inequality in COVID-19: a computational model 18 Mar 2021Journal of Applied PhysiologyReply to Xu et al. 16 Aug 2021Journal of Applied PhysiologyCited ByReply to Xu et al.Mattia Busana16 August 2021 | Journal of Applied Physiology, Vol. 131, No. 2 More from this issue > Volume 131Issue 2August 2021Pages 868-869 Crossmark Copyright & PermissionsCopyright © 2021 the American Physiological Society.https://doi.org/10.1152/japplphysiol.00388.2021PubMed34397292History Received 3 June 2021 Accepted 14 July 2021 Published online 16 August 2021 Published in print 1 August 2021 Metrics 1 CITATION 1 Total citation 0 Recent citations n/a Field Citation Ratio 0.14 Relative Citation Ratio publications1supporting0mentioning0contrasting0Smart Citations1000Citing PublicationsSupportingMentioningContrastingView CitationsSee how this article has been cited at scite.aiscite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made. 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DOI: 10.1152/japplphysiol.00388.2021
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W3193992153
Cites: 4
Cited by: 1
Related to: 10