{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:30:44Z","timestamp":1790825444540,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with an impaired autonomic nervous system and vagus nerve function. Electrical or physiological (deep breathing\u2014DB) vagus nerve stimulation (VNS) could be a potential treatment approach, but no direct comparison has been made. In this study, the effect of transcutaneous auricular VNS (taVNS) and DB on vagal tone was compared in healthy participants and RA or SLE patients. The vagal tone was estimated using time-domain heart-rate variability (HRV) parameters. Forty-two healthy participants and 52 patients performed 30 min of DB and 30 min of taVNS on separate days. HRV was recorded before and immediately after each intervention. For the healthy participants, all HRV parameters increased after DB (SDNN + RMSSD: 21\u201346%), while one HRV parameter increased after taVNS (SDNN: 16%). For the patients, all HRV parameters increased after both DB (17\u201331%) and taVNS (18\u201325%), with no differences between the two types of VNS. DB was associated with the largest elevation of the HRV parameters in healthy participants, while both types of VNS led to elevated HRV parameters in the patients. The findings support a potential use of VNS as a new treatment approach, but the clinical effects need to be investigated in future studies.<\/jats:p>","DOI":"10.3390\/s22207884","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:31:01Z","timestamp":1666053061000},"page":"7884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Modulating Heart Rate Variability through Deep Breathing Exercises and Transcutaneous Auricular Vagus Nerve Stimulation: A Study in Healthy Participants and in Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus"],"prefix":"10.3390","volume":"22","author":[{"given":"Mette Kjeldsgaard","family":"Jensen","sequence":"first","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally S\u00f8gaard","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine S\u00f8gaard","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Hundborg","family":"Liboriussen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5812-5234","authenticated-orcid":false,"given":"Salome","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-4359","authenticated-orcid":false,"given":"Mads","family":"Jochumsen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","article-title":"Rheumatoid arthritis","volume":"376","author":"Scott","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMra1100359","article-title":"Systemic Lupus Erythematosus","volume":"365","author":"Tsokos","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.semarthrit.2014.05.001","article-title":"The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: A systematic review and meta-analysis","volume":"44","author":"Matcham","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.rdc.2009.12.006","article-title":"Health-related quality of life and employment among persons with systemic lupus erythematosus","volume":"36","author":"Yazdany","year":"2010","journal-title":"Rheum. Dis. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10198-007-0088-8","article-title":"The burden of rheumatoid arthritis and access to treatment: Health burden and costs","volume":"8","author":"Lundkvist","year":"2008","journal-title":"Eur. J. Health Econ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: A review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/annrheumdis-2020-218272","article-title":"Update on the diagnosis and management of systemic lupus erythematosus","volume":"80","author":"Fanouriakis","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ejmech.2018.09.027","article-title":"Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review","volume":"158","author":"Wang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/03009742.2017.1314001","article-title":"Vagal influences in rheumatoid arthritis","volume":"47","author":"Rasmussen","year":"2018","journal-title":"Scand. J. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/joim.12626","article-title":"Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis","volume":"282","author":"Koopman","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1113\/JP271539","article-title":"Anti-inflammatory properties of the vagus nerve: Potential therapeutic implications of vagus nerve stimulation","volume":"594","author":"Bonaz","year":"2016","journal-title":"J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/0961203306076223","article-title":"Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sj\u00f6gren syndrome and other autoimmune diseases","volume":"16","author":"Stojanovich","year":"2007","journal-title":"Lupus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ebiom.2016.02.029","article-title":"Autonomic dysfunction precedes development of rheumatoid arthritis: A prospective cohort study","volume":"6","author":"Koopman","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/0002-8703(94)90059-0","article-title":"Heart rate variability: A measure of cardiac autonomic tone","volume":"127","author":"Stein","year":"1994","journal-title":"Am. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102894","DOI":"10.1016\/j.autneu.2021.102894","article-title":"Transcutaneous auricular vagus nerve stimulation and heart rate variability: Analysis of parameters and targets","volume":"236","author":"Machetanz","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105002","DOI":"10.1088\/1361-6579\/ac24e6","article-title":"Bursted auricular vagus nerve stimulation alters heart rate variability in healthy subjects","volume":"42","author":"Kampusch","year":"2021","journal-title":"Physiol. Meas."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.brs.2017.05.006","article-title":"Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial","volume":"10","author":"Antonino","year":"2017","journal-title":"Brain Stimul."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.autneu.2016.11.003","article-title":"Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects","volume":"203","author":"Cserjesi","year":"2017","journal-title":"Auton. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Borges, U., Laborde, S., and Raab, M. (2019). Influence of transcutaneous vagus nerve stimulation on cardiac vagal activity: Not different from sham stimulation and no effect of stimulation intensity. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223848"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"599896","DOI":"10.3389\/fphys.2020.599896","article-title":"Sympathetic effect of auricular transcutaneous vagus nerve stimulation on healthy subjects: A crossover controlled clinical trial comparing vagally mediated and active control stimulation using microneurography","volume":"11","author":"Gauthey","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13933","DOI":"10.1111\/psyp.13933","article-title":"Does transcutaneous auricular vagus nerve stimulation affect vagally mediated heart rate variability? A living and interactive Bayesian meta-analysis","volume":"58","author":"Wolf","year":"2021","journal-title":"Psychophysiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.brs.2020.03.011","article-title":"Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation","volume":"13","author":"Sclocco","year":"2020","journal-title":"Brain Stimul."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13571","DOI":"10.1111\/psyp.13571","article-title":"Moving beyond belief: A narrative review of potential biomarkers for transcutaneous vagus nerve stimulation","volume":"57","author":"Burger","year":"2020","journal-title":"Psychophysiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12999","DOI":"10.1111\/nmo.12999","article-title":"Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha","volume":"29","author":"Brock","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/ner.12398","article-title":"Noninvasive transcutaneous vagus nerve stimulation decreases whole blood culture-derived cytokines and chemokines: A randomized, blinded, healthy control pilot trial","volume":"19","author":"Lerman","year":"2016","journal-title":"Neuromodul. Technol. Neural Interface"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13075-015-0667-5","article-title":"Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: A randomized controlled study","volume":"17","author":"Kox","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8284","DOI":"10.1073\/pnas.1605635113","article-title":"Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis","volume":"113","author":"Koopman","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1136\/annrheumdis-2020-217872","article-title":"Transcutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: A randomised, double-blind, sham-controlled pilot trial","volume":"80","author":"Aranow","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/03009742.2020.1764617","article-title":"Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: Results of a pilot study","volume":"50","author":"Drewes","year":"2021","journal-title":"Scand. J. Rheumatol."},{"key":"ref_30","first-page":"503","article-title":"Acute effects on cardiovascular oscillations during controlled slow yogic breathing","volume":"145","author":"Bhagat","year":"2017","journal-title":"Indian J. Med. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3389\/fphys.2018.01341","article-title":"Optimization of vagal stimulation protocol based on spontaneous breathing rate","volume":"9","author":"Ferreira","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-016-1286-7","article-title":"Yogic breathing when compared to attention control reduces the levels of pro-inflammatory biomarkers in saliva: A pilot randomized controlled trial","volume":"16","author":"Twal","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.3233\/BMR-200190","article-title":"Influence of respiration frequency on heart rate variability parameters: A randomized cross-sectional study","volume":"34","author":"Soer","year":"2021","journal-title":"J. Back Musculoskelet. Rehabil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"110569","DOI":"10.1016\/j.jpsychores.2021.110569","article-title":"Investigating components of pranayama for effects on heart rate variability","volume":"148","author":"Sharpe","year":"2021","journal-title":"J. Psychosom. Res."},{"key":"ref_35","first-page":"107","article-title":"Slow deep breathing increases pain-tolerance and modulates cardiac autonomic nervous system","volume":"61","author":"Sharma","year":"2017","journal-title":"Indian J. Physiol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/RHU.0000000000001300","article-title":"Deep Breathing Increases Heart Rate Variability in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus","volume":"27","author":"Rovsing","year":"2021","journal-title":"J. Clin. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liboriussen, C.H., Andersen, S.S., Andersen, S.S., Jensen, M.K., Jochumsen, M., and Kristensen, S. (2022). Investigating the Dose-Response Relationship between Deep Breathing and Heart Rate Variability in Healthy Participants and Across-Days Reliability in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus. Sensors, 22.","DOI":"10.3390\/s22186849"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1183\/20734735.009817","article-title":"The physiological effects of slow breathing in the healthy human","volume":"13","author":"Russo","year":"2017","journal-title":"Breathe"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s42234-019-0020-4","article-title":"Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear","volume":"5","author":"Addorisio","year":"2019","journal-title":"Bioelectron. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102893","DOI":"10.1016\/j.autneu.2021.102893","article-title":"Effects of transcutaneous auricular vagus nerve stimulation on cardiovascular autonomic control in health and disease","volume":"236","author":"Carandina","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.berh.2014.10.015","article-title":"Vagus nerve stimulation: A new bioelectronics approach to treat rheumatoid arthritis?","volume":"28","author":"Koopman","year":"2014","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000435843","article-title":"Modulation of the innate immune response through the vagus nerve","volume":"131","author":"Kox","year":"2015","journal-title":"Nephron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1476-511X-10-19","article-title":"Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus?","volume":"10","author":"Das","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1365-2796.2010.02321.x","article-title":"The pulse of inflammation: Heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy","volume":"269","author":"Huston","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1136\/gutjnl-2013-306698","article-title":"Preliminary report: Modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity","volume":"64","author":"Botha","year":"2015","journal-title":"Gut"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability: Standards of measurement, physiological interpretation, and clinical use","volume":"17","author":"Malik","year":"1996","journal-title":"Eur. Heart J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vollmer, M. (2019, January 8\u201311). HRVTool\u2014An Open-Source Matlab Toolbox for Analyzing Heart Rate Variability. Proceedings of the 2019 Computing in Cardiology (CinC), Singapore.","DOI":"10.22489\/CinC.2019.032"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fpubh.2017.00258","article-title":"An overview of heart rate variability metrics and norms","volume":"5","author":"Shaffer","year":"2017","journal-title":"Front. Public Health"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.brs.2014.07.031","article-title":"Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity","volume":"7","author":"Clancy","year":"2014","journal-title":"Brain Stimul."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/BF02322053","article-title":"Standardized tests of heart rate variability: Normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate","volume":"11","author":"Agelink","year":"2001","journal-title":"Clin. Auton. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102886","DOI":"10.1016\/j.autneu.2021.102886","article-title":"Transdermal auricular vagus stimulation for the treatment of postural tachycardia syndrome","volume":"236","author":"Diedrich","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9933532","DOI":"10.1155\/2021\/9933532","article-title":"Vagal nerve stimulation-modulation of the anti-inflammatory response and clinical outcome in psoriatic arthritis or ankylosing spondylitis","volume":"2021","author":"Brock","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Venborg, J., Wegeberg, A.M., Kristensen, S., Brock, B., Brock, C., and Pfeiffer-Jensen, M. (2021). The Effect of Transcutaneous Vagus Nerve Stimulation in Patients with Polymyalgia Rheumatica. Pharmaceuticals, 14.","DOI":"10.3390\/ph14111166"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ca.1089","article-title":"The nerve supply of the human auricle","volume":"15","author":"Peuker","year":"2002","journal-title":"Clin. Anat."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1136\/heart.88.4.378","article-title":"The pNNx files: Re-examining a widely used heart rate variability measure","volume":"88","author":"Mietus","year":"2002","journal-title":"Heart"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.autneu.2008.05.005","article-title":"Heart rate variability predicts anti-tumor necrosis factor therapy response for inflammatory arthritis","volume":"143","author":"Holman","year":"2008","journal-title":"Auton. Neurosci."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/22\/20\/7884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:43Z","timestamp":1760144143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/22\/20\/7884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":56,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["s22207884"],"URL":"https:\/\/doi.org\/10.3390\/s22207884","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]}}}