{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:30:35Z","timestamp":1790883035866,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ARM"],"abstract":"<jats:p>Background: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19. Aim: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness. Methods: In total, 33 patients (mean \u00b1 SD, 53 \u00b1 11 years) with long COVID-19 were recruited 149 \u00b1 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV\/TLC \u2265 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN2W). Results: CC was 115 \u00b1 28% pred. and open capacity (OC) was 90 \u00b1 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 \u00b1 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010). Conclusions: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.<\/jats:p>","DOI":"10.3390\/arm92050031","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T10:01:51Z","timestamp":1724666511000},"page":"329-337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Small Airways Dysfunction and Lung Hyperinflation in Long COVID-19 Patients as Potential Mechanisms of Persistent Dyspnoea"],"prefix":"10.3390","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5794-3089","authenticated-orcid":false,"given":"Angelos","family":"Vontetsianos","sequence":"first","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-6974","authenticated-orcid":false,"given":"Nikolaos","family":"Chynkiamis","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Thorax Research Foundation, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0925-4046","authenticated-orcid":false,"given":"Christina","family":"Anagnostopoulou","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Lekka","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavrina","family":"Zaneli","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4925-2332","authenticated-orcid":false,"given":"Nektarios","family":"Anagnostopoulos","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0138-5582","authenticated-orcid":false,"given":"Nikoleta","family":"Rovina","sequence":"additional","affiliation":[{"name":"1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos F.","family":"Kampolis","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, \u201cHippokration\u201d General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9708-3241","authenticated-orcid":false,"given":"Andriana I.","family":"Papaioannou","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6852-1553","authenticated-orcid":false,"given":"Georgios","family":"Kaltsakas","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Lane Fox Respiratory Service, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London SE1 7EH, UK"},{"name":"Centre of Human and Applied Physiological Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4830-7207","authenticated-orcid":false,"given":"Ioannis","family":"Vogiatzis","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University Newcastle, Newcastle upon Tyne NE1 8ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5861-3454","authenticated-orcid":false,"given":"Grigorios","family":"Stratakos","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-9656","authenticated-orcid":false,"given":"Petros","family":"Bakakos","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-7220","authenticated-orcid":false,"given":"Nikolaos","family":"Koulouris","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, 1st Respiratory Medicine Department, \u201cSotiria\u201d Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","unstructured":"Johns Hopkins University (2023, October 03). Coronavirus Resource Centre. Available online: https:\/\/coronavirus.jhu.edu\/map.html."},{"key":"ref_2","first-page":"20","article-title":"COVID-19 pandemic: From origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management","volume":"29","author":"Ochani","year":"2021","journal-title":"Infez. Med."},{"key":"ref_3","unstructured":"NICE (2023, October 25). COVID-19 Rapid Guideline: Managing the Longterm Effects of COVID-19. Available online: https:\/\/www.nice.org.uk\/guidance\/ng188\/chapter\/1-Identification."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13256-023-03800-9","article-title":"Management, control, and decision making in unexpected recurrent venous thromboembolism in COVID-19: A case report","volume":"17","author":"Heshmatnia","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s42399-022-01273-3","article-title":"Pulmonary Embolism in Post-CoviD-19 Patients, a Literature Review: Red Flag for Increased Awareness?","volume":"4","author":"Mouzarou","year":"2022","journal-title":"SN Compr. Clin. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0140-6736(20)32656-8","article-title":"6-month consequences of COVID-19 in patients discharged from hospital: A cohort study","volume":"397","author":"Huang","year":"2021","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.pulmoe.2020.10.013","article-title":"Respiratory function in patients post-infection by COVID-19: A systematic review and meta-analysis","volume":"27","author":"Burgos","year":"2021","journal-title":"Pulmonology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101668","DOI":"10.1016\/j.eclinm.2022.101668","article-title":"Lung-function trajectories in COVID-19 survivors after discharge: A two-year longitudinal cohort study","volume":"54","author":"Zhang","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_9","first-page":"e928996","article-title":"Long-Term Respiratory and Neurological Sequelae of COVID-19","volume":"26","author":"Wang","year":"2020","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1007\/s15010-021-01718-2","article-title":"Long-term changes in pulmonary function among patients surviving to COVID-19 pneumonia","volume":"50","author":"Fumagalli","year":"2022","journal-title":"Infection"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s-Telles, A., L\u00f3pez-Romero, S., Figueroa-Hurtado, E., Pou-Aguilar, Y.N., Wong, A.W., Milne, K.M., Ryerson, C.J., and Guenette, J.A. (2021). Pulmonary function and functional capacity in COVID-19 survivors with persistent dyspnoea. Respir. Physiol. Neurobiol., 288.","DOI":"10.1016\/j.resp.2021.103644"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1001\/jama.2020.12603","article-title":"Persistent Symptoms in Patients after Acute COVID-19","volume":"324","author":"Bernabei","year":"2020","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lopes, A.J., Litrento, P.F., Provenzano, B.C., Carneiro, A.S., Monnerat, L.B., da Cal, M.S., Ghetti, A.T.A., and Mafort, T.T. (2021). Small airway dysfunction on impulse oscillometry and pathological signs on lung ultrasound are frequent in post-COVID-19 patients with persistent respiratory symptoms. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260679"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s00508-022-02137-5","article-title":"Relationship between exercise capacity and impulse oscillometry parameters after COVID-19 infections","volume":"135","author":"Candemir","year":"2023","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_15","first-page":"e187","article-title":"Long-term respiratory outcomes after COVID-19: A Brazilian cohort study","volume":"46","author":"Visconti","year":"2022","journal-title":"Rev. Panam. Salud Publica Pan Am. J. Public Health"},{"key":"ref_16","first-page":"7919033","article-title":"The Importance of Radiological Patterns and Small Airway Disease in Long-Term Follow-Up of Postacute COVID-19: A Preliminary Study","volume":"2022","author":"Mogami","year":"2022","journal-title":"Radiol. Res. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s12931-024-02830-1","article-title":"Long COVID symptoms after 8-month recovery: Persistent static lung hyperinflation associated with small airway dysfunction","volume":"25","author":"Lo","year":"2024","journal-title":"Respir. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"McNulty, W., and Usmani, O.S. (2014). Techniques of assessing small airways dysfunction. Eur. Clin. Respir. J., 1.","DOI":"10.3402\/ecrj.v1.25898"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/j.rmed.2013.05.003","article-title":"Techniques for assessing small airways function: Possible applications in asthma and COPD","volume":"119","author":"Kostikas","year":"2016","journal-title":"Respir. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1183\/09031936.00069712","article-title":"Consensus statement for inert gas washout measurement using multiple- and single- breath tests","volume":"41","author":"Robinson","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.chest.2016.05.019","article-title":"Single-Breath Washout Tests to Assess Small Airway Disease in COPD","volume":"150","author":"Boeck","year":"2016","journal-title":"Chest"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00421-006-0389-0","article-title":"Closing volume: A reappraisal (1967\u20132007)","volume":"99","author":"Torchio","year":"2007","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4103\/amsr.amsr_2_23","article-title":"Small airway disease: A new \u201cphenotype\u201d of obstructive airway disease","volume":"2","author":"Patil","year":"2023","journal-title":"Ann. Med. Sci. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1164\/ajrccm.150.6.7952618","article-title":"Dependence of maximal flow-volume curves on time course of preceding inspiration in patients with chronic obstruction pulmonary disease","volume":"150","author":"Prandi","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","unstructured":"ERS (1993). Standardized lung function testing. Official statement of the European Respiratory Society. Eur. Respir. J. Suppl., 16, 1\u2013100."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1183\/09031936.05.00034905","article-title":"Standardisation of the single-breath determination of carbon monoxide uptake in the lung","volume":"26","author":"Macintyre","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1183\/09031936.06.00040506","article-title":"Inspiratory fraction and exercise impairment in COPD patients GOLD stages II-III","volume":"28","author":"Albuquerque","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29S","DOI":"10.1378\/chest.63.4_Supplement.29S","article-title":"Closing volume as a simple, sensitive test for the detection of peripheral airway disease","volume":"63","author":"Buist","year":"1973","journal-title":"Chest"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1378\/chest.93.3.580","article-title":"Evaluation of clinical methods for rating dyspnea","volume":"93","author":"Mahler","year":"1988","journal-title":"Chest"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1148\/radiol.212170","article-title":"Quantitative Chest CT Assessment of Small Airways Disease in Post-Acute SARS-CoV-2 Infection","volume":"304","author":"Cho","year":"2022","journal-title":"Radiology"},{"key":"ref_31","first-page":"850","article-title":"Incidence and follow-up of persistent lung perfusion abnormalities as a result of suspected air trapping or microthrombosis in non-hospitalised COVID-19 patients during the early half of the pandemic\u2014Experience in a tertiary institution in South Afr","volume":"112","author":"Evbuomwan","year":"2022","journal-title":"S. Afr. Med. J. Suid-Afr. Tydskr. Vir Geneeskd."},{"key":"ref_32","first-page":"1299","article-title":"Inspiratory and Expiratory Chest High-resolution CT: Small-airway Disease Evaluation in Patients with COVID-19","volume":"17","author":"Huang","year":"2021","journal-title":"Curr. Med. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107532","DOI":"10.1016\/j.rmed.2024.107532","article-title":"Small airways in asthma: From inflammation and pathophysiology to treatment response","volume":"222","author":"Siora","year":"2024","journal-title":"Respir. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1398-9995.2006.00970.x","article-title":"Nitrogen washout slope in poorly controlled asthma","volume":"61","author":"Bourdin","year":"2006","journal-title":"Allergy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S2213-2600(17)30207-2","article-title":"Frequency of exacerbations in patients with chronic obstructive pulmonary disease: An analysis of the SPIROMICS cohort","volume":"5","author":"Han","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S2213-2600(21)00536-1","article-title":"The role of small airway dysfunction in asthma control and exacerbations: A longitudinal, observational analysis using data from the ATLANTIS study","volume":"10","author":"Kraft","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S2213-2600(23)00159-5","article-title":"Respiratory sequelae of COVID-19: Pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation","volume":"11","author":"Singh","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1136\/jcp.2003.013276","article-title":"Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)","volume":"57","author":"Tse","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ortiz, M.E., Thurman, A., Pezzulo, A.A., Leidinger, M.R., Klesney-Tait, J.A., Karp, P.H., Tan, P., Wohlford-Lenane, C., McCray, P.B., and Meyerholz, D.K. (2020). Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract. EBioMedicine, 60.","DOI":"10.1016\/j.ebiom.2020.102976"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s15010-020-01474-9","article-title":"Pulmonary function in patients surviving to COVID-19 pneumonia","volume":"49","author":"Fumagalli","year":"2021","journal-title":"Infection"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109676","DOI":"10.1016\/j.ejrad.2021.109676","article-title":"Post-discharge chest CT findings and pulmonary function tests in severe COVID-19 patients","volume":"138","author":"Balbi","year":"2021","journal-title":"Eur. J. Radiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1016\/j.mayocp.2021.03.016","article-title":"Why We Should Target Small Airways Disease in Our Management of Chronic Obstructive Pulmonary Disease","volume":"96","author":"Usmani","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e222557","DOI":"10.1148\/radiol.222557","article-title":"Postacute COVID-19 Syndrome: 129Xe MRI Ventilation Defects and Respiratory Outcomes 1 Year Later","volume":"307","author":"Kooner","year":"2023","journal-title":"Radiology"}],"container-title":["Advances in Respiratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2543-6031\/92\/5\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:21Z","timestamp":1760110941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2543-6031\/92\/5\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["arm92050031"],"URL":"https:\/\/doi.org\/10.3390\/arm92050031","relation":{},"ISSN":["2543-6031"],"issn-type":[{"value":"2543-6031","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,23]]}}}