The Role of Small Airways in Respiratory Failure Caused by Covid-19 Infection
Main Article Content
Abstract
Small airways are the “silent zone” of lungs because there is a limited range of methods to assess their function. At the same time this lung zone plays an important role in local distribution between ventilation and perfusion, that in turn influences the effectiveness of gas exchange. Small airways are incorporated into the lung elastic network and their patency is strongly influenced by the pathological processes that occur in lung parenchyma.
ACE2 receptors which are the bindng sites for SARS-Cov-2 virus most densly are located on the epihelium of upper airways, second type alveolocytes and club cells. Damage to mucosa of pharynx and proximal bronchi explains the symptoms of mild covid-19 disease, but affections to alveolar epthelium opens the access to pulmonary vessels which increase permeability inducing interstitial oedema, initiate infiltration of lung interstitium with inflammatory cells and release from endothelial cells vasodilatory mediators which in turn inactivate the mechanism of hypoxic pu;monary vasoconstriction.
Ventilation/perfusion mismatch in favour of perfusion that develpops as the consequence of described events leads to intrapulmonary blood shunting, arterial hypoxaemia and severe dispnoea that poorely associates with mild changes in X-ray examination findings.
Progressing of parenchymal inflammation further increases the pulmonary vascular permeability that recruits more alveoli, increases the lung weight and affects gas diffusion through alveolo-capillary membrane making hypoxemia more severe.
During the acute period of covid-19 pneumonia small airways demonstrate more functional rather than organic obstruction. However, during the post-acute period proliferation of bronchiolar epitelial cells occurs, they transdifferentiate and ingrow into alveolar space and initiate lung and airways fibrosis.
This review has summarized recent research findings that uncover the small airways role in different pathogenetic mechanisms involved in the course of covid-19 infection both in acute and recovery period.
Article Details
How to Cite
IMMANUELS, Taivans; GUNTA, Strazda; NORMUNDS, Jurka.
The Role of Small Airways in Respiratory Failure Caused by Covid-19 Infection.
Medical Research Archives, [S.l.], v. 11, n. 7.1, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3980>. Date accessed: 15 may 2024.
doi: https://doi.org/10.18103/mra.v11i7.1.3980.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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13. Liu Y, Qu HQ, Qu J, Tian L, Hakonarson H. Expression Pattern of the SARS-CoV-2 Entry Genes ACE2 and TMPRSS2 in the Respiratory Tract. Viruses. 2020;12(10).
14. Chen Q, Langenbach S, Li M, et al. ACE2 Expression in Organotypic Human Airway Epithelial Cultures and Airway Biopsies. Frontiers in pharmacology. 2022;13:813087.
15. Stelzig KE, Canepa-Escaro F, Schiliro M, Berdnikovs S, Prakash YS, Chiarella SE. Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells. American journal of physiology Lung cellular and molecular physiology. 2020;318(6):L1280-l1281.
16. Aksoy H, Karadag AS, Wollina U. Angiotensin II receptors: Impact for COVID-19 severity. Dermatologic therapy. 2020;33(6):e13989.
17. Karnik SS, Singh KD, Tirupula K, Unal H. Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22. British journal of pharmacology. 2017;174(9):737-753.
18. Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Critical Care. 2020;24(1):422.
19. Gierhardt M, Pak O, Walmrath D, et al. Impairment of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome. European Respiratory Review. 2021;30(161):210059.
20. Lumb AB, Slinger P. Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications. Anesthesiology. 2015;122(4):932-946.
21. Borczuk AC, Salvatore SP, Seshan SV, et al. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2020;33(11):2156-2168.
22. Menter T, Haslbauer JD, Nienhold R, et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198-209.
23. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. The New England journal of medicine. 2020;383(2):120-128.
24. Mauad T, Duarte-Neto AN, da Silva LFF, et al. Tracking the time course of pathological patterns of lung injury in severe COVID-19. Respiratory research. 2021;22(1):32.
25. Stoyanov GS, Yanulova N, Stoev L, et al. Temporal Patterns of COVID-19-Associated Pulmonary Pathology: An Autopsy Study. Cureus. 2021;13(12):e20522.
26. Boers JE, Ambergen AW, Thunnissen FB. Number and proliferation of clara cells in normal human airway epithelium. American journal of respiratory and critical care medicine. 1999;159(5 Pt 1):1585-1591.
27. Rokicki W, Rokicki M, Wojtacha J, Dżeljijli A. The role and importance of club cells (Clara cells) in the pathogenesis of some respiratory diseases. Kardiochirurgia i torakochirurgia polska = Polish journal of cardio-thoracic surgery. 2016;13(1):26-30.
28. Doglioni C, Ravaglia C, Chilosi M, et al. Covid-19 Interstitial Pneumonia: Histological and Immunohistochemical Features on Cryobiopsies. Respiration; international review of thoracic diseases. 2021;100(6):488-498.
29. Magro C, Mulvey JJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational research : the journal of laboratory and clinical medicine. 2020;220:1-13.
30. Lang M, Som A, Mendoza DP, et al. Hypoxaemia related to COVID-19: vascular and perfusion abnormalities on dual-energy CT. The Lancet Infectious diseases. 2020;20(12):1365-1366.
31. Huang R, Zhu J, Zhou J, et al. Inspiratory and Expiratory Chest High-resolution CT: Small-airway Disease Evaluation in Patients with COVID-19. Current medical imaging. 2021;17(11):1299-1307.
32. Tarraso J, Safont B, Carbonell-Asins JA, et al. Lung function and radiological findings 1 year after COVID-19: a prospective follow-up. Respiratory research. 2022;23(1):242.
33. Franquet T, Giménez A, Ketai L, et al. Air trapping in COVID-19 patients following hospital discharge: retrospective evaluation with paired inspiratory/expiratory thin-section CT. Eur Radiol. 2022;32(7):4427-4436.
34. Jia X, Han X, Cao Y, et al. Quantitative inspiratory-expiratory chest CT findings in COVID-19 survivors at the 6-month follow-up. Sci Rep. 2022;12(1):7402.
35. Cho JL, Villacreses R, Nagpal P, et al. Quantitative Chest CT Assessment of Small Airways Disease in Post-Acute SARS-CoV-2 Infection. Radiology. 2022;304(1):185-192.
36. Maniscalco M, Ambrosino P, Fuschillo S, et al. Bronchodilator reversibility testing in post-COVID-19 patients undergoing pulmonary rehabilitation. Respiratory Medicine. 2021;182:106401.
37. Chakraborty A, Mastalerz M, Ansari M, Schiller HB, Staab-Weijnitz CA. Emerging Roles of Airway Epithelial Cells in Idiopathic Pulmonary Fibrosis. Cells. 2022;11(6).
38. Verleden SE, Tanabe N, McDonough JE, et al. Small airways pathology in idiopathic pulmonary fibrosis: a retrospective cohort study. The Lancet Respiratory medicine. 2020;8(6):573-584.
39. Doerner AM, Zuraw BL. TGF-β1 induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids. Respiratory research. 2009;10(1):100.
40. Tian B, Li X, Kalita M, et al. Analysis of the TGFβ-induced program in primary airway epithelial cells shows essential role of NF-κB/RelA signaling network in type II epithelial mesenchymal transition. BMC genomics. 2015;16(1):529.
41. Yun E, Kook Y, Yoo KH, et al. Endothelial to Mesenchymal Transition in Pulmonary Vascular Diseases. Biomedicines. 2020;8(12).
42. Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(35):13180-13185.
43. Strickland NH, Hughes JM, Hart DA, Myers MJ, Lavender JP. Cause of regional ventilation-perfusion mismatching in patients with idiopathic pulmonary fibrosis: a combined CT and scintigraphic study. AJR American journal of roentgenology. 1993;161(4):719-725.
44. Ikezoe K, Hackett TL, Peterson S, et al. Small Airway Reduction and Fibrosis Is an Early Pathologic Feature of Idiopathic Pulmonary Fibrosis. American journal of respiratory and critical care medicine. 2021;204(9):1048-1059.
45. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.
46. Akira M. Radiographic Differentiation of Advanced Fibrocystic Lung Diseases. Annals of the American Thoracic Society. 2017;14(3):432-440.
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