{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:04:04Z","timestamp":1790114644827,"version":"4.0.1"},"reference-count":22,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI\/TTOT) and by the VT\/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI\/TTOT and VT\/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p &lt; 0.05). LC patients also showed significantly higher values of TI\/TTOT at rest and at peak, and lower values in VT\/TI at peak (p &lt; 0.05). In LC patients, values of TI\/TTOT at peak were significantly related to \u2206PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p &lt; 0.05). When LC patients were categorized by the TI\/TTOT 0.38 cut-off value, patients with TI\/TTOT &gt; 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation\/CO2 linear relationship slope than patients with TI\/TTOT \u2264 0.38 (p &lt; 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.<\/jats:p>","DOI":"10.3390\/jcm11247388","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T03:32:32Z","timestamp":1670902352000},"page":"7388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea"],"prefix":"10.3390","volume":"11","author":[{"given":"Annalisa","family":"Frizzelli","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Cardio-Thoracic and Vascular Department, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Spigno","sequence":"additional","affiliation":[{"name":"Cardiac Unit, \u201cG. da Saliceto\u201d Hospital of Piacenza, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Moderato","sequence":"additional","affiliation":[{"name":"Cardiac Unit, \u201cG. da Saliceto\u201d Hospital of Piacenza, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geza","family":"Halasz","sequence":"additional","affiliation":[{"name":"Cardiac Unit, \u201cG. da Saliceto\u201d Hospital of Piacenza, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-5345","authenticated-orcid":false,"given":"Marina","family":"Aiello","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Cardio-Thoracic and Vascular Department, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-1035","authenticated-orcid":false,"given":"Panagiota","family":"Tzani","sequence":"additional","affiliation":[{"name":"Cardio-Thoracic and Vascular Department, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Manari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-069X","authenticated-orcid":false,"given":"Luigino","family":"Calzetta","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5552-2912","authenticated-orcid":false,"given":"Roberta","family":"Pisi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-7281","authenticated-orcid":false,"given":"Giovanna","family":"Pel\u00e0","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Department of General and Specialistic Medicine, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Piepoli","sequence":"additional","affiliation":[{"name":"Clinical Cardiology Unit, Policlinico San Donato, University of Milan, 20122 Milan, Italy"},{"name":"Department of Preventive Cardiology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Chetta","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Cardio-Thoracic and Vascular Department, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","unstructured":"(2020). COVID-19 Rapid Guideline: Managing the Long-Term Effects of COVID-19, National Institute for Health and Care Excellence (NICE). ISBN-13: 978-1-4731-3943-5."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"2100996","DOI":"10.1183\/13993003.00996-2021","article-title":"Cardiopulmonary exercise capacity and limitations 3 months after COVID-19 hospitalisation","volume":"58","author":"Ankerstjerne","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2100870","DOI":"10.1183\/13993003.00870-2021","article-title":"Deconditioning as main mechanism of impaired exercise response in COVID-19 survivors","volume":"58","author":"Rinaldo","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2101578","DOI":"10.1183\/13993003.01578-2021","article-title":"Hyperventilation as one of the mechanisms of persistent dyspnoea in SARS-CoV-2 survivors","volume":"58","author":"Motiejunaite","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jchf.2021.10.002","article-title":"Use of Cardiopulmonary Stress Testing for Patients with Unexplained Dyspnea Post-Coronavirus Disease","volume":"9","author":"Mancini","year":"2021","journal-title":"JACC Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e001126","DOI":"10.1136\/bmjresp-2021-001126","article-title":"Dysfunctional breathing diagnosed by cardiopulmonary exercise testing in \u2018long COVID\u2019 patients with persistent dyspnoea","volume":"9","author":"Genecand","year":"2022","journal-title":"BMJ Open Respir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e15197","DOI":"10.14814\/phy2.15197","article-title":"Classification and occurrence of an abnormal breathing pattern during cardiopulmonary exercise testing in subjects with persistent symptoms following COVID-19 disease","volume":"10","author":"Nylander","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_9","first-page":"53","article-title":"Getting to grips with \u2018dysfunctional breathing\u2019","volume":"16","author":"Barker","year":"2015","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1183\/16000617.0088-2015","article-title":"Dysfunctional breathing: A review of the literature and proposal for classification","volume":"25","author":"Boulding","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF01709831","article-title":"Breathing pattern analysis","volume":"18","author":"Tobin","year":"1992","journal-title":"Intensive Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1748-1716.1984.tb07381.x","article-title":"Breathing pattern and lung volumes during exercise","volume":"120","author":"Lind","year":"1984","journal-title":"Acta Physiol. Scand."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E70","DOI":"10.1164\/rccm.201908-1590ST","article-title":"Standardization of spirometry 2019 update an official American Thoracic Society and European Respiratory Society technical statement","volume":"200","author":"Graham","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1183\/09041950.005s1693","article-title":"Lung volumes and forced ventilatory flows. Report working party standardization of lung function tests, European community for steel and oral official statement of the European respiratory society","volume":"6","author":"Quanjer","year":"1993","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1164\/ajrccm.167.10.950","article-title":"ATS\/ACCP Statement on cardiopulmonary exercise testing","volume":"167","author":"Ross","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","unstructured":"Wasserman, K., Hansen, J.E., Sue, D.Y., Casaburi, R., and Whipp, B.J. (1994). Normal values. Principles of Exercise Testing & Interpretation, Lippincott Williams & Wilkins."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/S0735-1097(96)00412-3","article-title":"Oxygen uptake efficiency slope: A new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise","volume":"28","author":"Baba","year":"1996","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1056\/NEJM199910283411804","article-title":"Heart-rate recovery immediately after exercise as a predictor of mortality","volume":"341","author":"Cole","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.chest.2021.08.010","article-title":"Persistent Exertional Intolerance After COVID-19: Insights from Invasive Cardiopulmonary Exercise Testing","volume":"161","author":"Singh","year":"2022","journal-title":"Chest"},{"key":"ref_20","first-page":"1196","article-title":"Evaluation of human diaphragm fatigue","volume":"53","author":"Bellemare","year":"1982","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1136\/thx.32.2.212","article-title":"Comparison of occlusion pressure and ventilatory responses","volume":"32","author":"Lederer","year":"1977","journal-title":"Thorax"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1183\/09031936.02.00063102","article-title":"Effects of mechanical ventilation on diaphragm function and biology","volume":"20","author":"Decramer","year":"2002","journal-title":"Eur. Respir. J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/24\/7388\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:40:11Z","timestamp":1760146811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/24\/7388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":22,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["jcm11247388"],"URL":"https:\/\/doi.org\/10.3390\/jcm11247388","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]}}}