{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:06:42Z","timestamp":1770455202159,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation of Korea (NRF) grant","award":["2018R1A2B6002810"],"award-info":[{"award-number":["2018R1A2B6002810"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA. We aimed to evaluate the impact of different doses of ASA on inflammation control while minimizing adverse effects in the acute phase treatment of KD. Methods: The enrolled 323 patients with KD were divided into three groups according to ASA dose: moderate-dose (30\u201350 mg\/kg\/day), high-dose (80\u2013100 mg\/kg\/day), and non-ASA. Results: High-dose ASA group showed a significantly shorter duration of fever from the start of treatment to remission than other groups. Baseline level and delta score of interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-\u03b1, and transforming growth factor \u03b2 were not statistically different among the groups. The number of patients who received additional treatments in the non-ASA group was more than other groups. Coronary artery dilatation was not significantly different among the groups. One patient with high-dose ASA was diagnosed with Reye syndrome. Conclusion: Different doses of ASA did not show any differences in changes of inflammatory bio-makers and cytokines. However, high-dose ASA showed occurrence of Reye syndrome, and non-ASA showed intravenous immunoglobulin refractoriness. We suggest that moderate-dose ASA may be beneficial for the treatment of patients in the acute phase of KD.<\/jats:p>","DOI":"10.3390\/children7100185","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T08:56:48Z","timestamp":1602838608000},"page":"185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Impact of Moderate-Dose Acetylsalicylic Acid in the Reduction of Inflammatory Cytokine and Prevention of Complication in Acute Phase of Kawasaki Disease: The Benefit of Moderate-Dose Acetylsalicylic Acid"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-3089","authenticated-orcid":false,"given":"Jung Eun","family":"Kwon","sequence":"first","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Children\u2019s Hospital, Daegu 41404, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da Eun","family":"Roh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Children\u2019s Hospital, Daegu 41404, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-574X","authenticated-orcid":false,"given":"Yeo Hyang","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Children\u2019s Hospital, Daegu 41404, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e927","DOI":"10.1161\/CIR.0000000000000484","article-title":"Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association","volume":"135","author":"McCrindle","year":"2017","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kuo, H.C., Lo, M.H., Hsieh, K.S., Guo, M.M.H., and Huanget, Y.H. (2015). High-dose aspirin is associated with anemia and does not confer benefit to disease outcomes in Kawasaki disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144603"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1016\/j.jacc.2015.12.073","article-title":"Kawasaki disease","volume":"67","author":"Newburger","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Research Committee of the Japanese Society of Pediatric Cardiology, and Cardiac Surgery Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki Disease (2014). Guidelines for medical treatment of acute Kawasaki disease: Report of the Research Committee of the Japanese Society of Pediatric C ardiology and Cardiac Surgery (2012 revised version). Pediatr. Int., 56, 135\u2013158.","DOI":"10.1111\/ped.12317"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e20170098","DOI":"10.1542\/peds.2017-0098","article-title":"Aspirin dose and prevention of coronary abnormalities in Kawasaki disease","volume":"139","author":"Dallaire","year":"2017","journal-title":"Pediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"182","DOI":"10.4070\/kcj.2013.43.3.182","article-title":"Is high-dose aspirin necessary in the acute phase of Kawasaki disease?","volume":"43","author":"Lee","year":"2013","journal-title":"Korean Circ. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"127","DOI":"10.24304\/kjcp.2017.27.3.127","article-title":"Drug Utilization in Korean Children with Kawasaki Disease","volume":"27","author":"Cha","year":"2017","journal-title":"Korean J. Clin. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3345\/kjp.2015.58.11.434","article-title":"Sensorineural hearing loss in patients with Kawasaki disease","volume":"58","author":"Park","year":"2015","journal-title":"Korean J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2165\/00148581-200709030-00008","article-title":"Aspirin and Reye syndrome: A review of the evidence","volume":"9","author":"Schror","year":"2007","journal-title":"Pediatr. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1440-1754.2005.00617.x","article-title":"Reye\u2019s syndrome developing in an infant on treatment of Kawasaki syndrome","volume":"41","author":"Wei","year":"2005","journal-title":"J. Paediatr. Child Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jpeds.2016.12.019","article-title":"Medium-or higher-dose acetylsalicylic acid for acute Kawasaki disease and patient outcomes","volume":"184","author":"Kim","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kuo, H.C., Guo, M.M.H., Lo, M.H., Hsieh, K.S., and Huang, Y.H. (2018). Effectiveness of intravenous immunoglobulin alone and intravenous immunoglobulin combined with high-dose aspirin in the acute stage of Kawasaki disease: Study protocol for a randomized controlled trial. BMC Pediatr., 18.","DOI":"10.1186\/s12887-018-1180-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1177\/000992280204100807","article-title":"Comparison of high-dose and low-dose aspirin plus intravenous immunoglobulin in the treatment of Kawasaki syndrome","volume":"41","author":"Saulsbury","year":"2002","journal-title":"Clin. Pediatr."},{"key":"ref_14","first-page":"209","article-title":"High-dose aspirin for Kawasaki disease: Outdated myth or effective aid?","volume":"35","author":"Amarilyo","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/art.37815","article-title":"Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1\/Th2 cytokine profiles in patients with Kawasaki disease","volume":"65","author":"Wang","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"516","DOI":"10.4070\/kcj.2015.45.6.516","article-title":"T-helper cytokine profiles in patients with Kawasaki disease","volume":"45","author":"Lee","year":"2015","journal-title":"Korean Circ. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10238-018-00544-5","article-title":"Interleukin-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive Kawasaki disease rather than coronary artery aneurysm","volume":"19","author":"Wu","year":"2019","journal-title":"Clin. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cca.2017.05.019","article-title":"TNF-\u03b1 is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease","volume":"471","author":"Hu","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1161\/CIRCGENETICS.110.940858","article-title":"Transforming growth factor-beta signaling pathway in patients with Kawasaki disease","volume":"4","author":"Shimizu","year":"2011","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.humpath.2012.05.004","article-title":"The role of TGF-\u03b2 and myofibroblasts in the arteritis of Kawasaki disease","volume":"44","author":"Shimizu","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/j.1365-2249.2004.02506.x","article-title":"Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease","volume":"137","author":"Kimura","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fphar.2017.00163","article-title":"Il-1 inhibition may have an important role in treating refractory Kawasaki disease","volume":"8","author":"Dusser","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.4049\/jimmunol.1801593","article-title":"TNF and IL-1 play essential but temporally distinct roles in driving cardiac inflammation in a murine model of Kawasaki disease","volume":"202","author":"Stock","year":"2019","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/cei.13314","article-title":"IL-1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis","volume":"198","author":"Gorelik","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e689","DOI":"10.1542\/peds.2004-1037","article-title":"Treatment of acute Kawasaki disease: Aspirin\u2019s role in the febrile stage revisited","volume":"114","author":"Hsieh","year":"2004","journal-title":"Pediatrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jjcc.2008.08.002","article-title":"The strategy of immune globulin resistant Kawasaki disease: A comparative study of additional immune globulin and steroid pulse therapy","volume":"53","author":"Ogata","year":"2009","journal-title":"J. Cardiol."},{"key":"ref_27","first-page":"780","article-title":"Management and outcome of intravenous gammaglobulin-resistant Kawasaki disease","volume":"47","author":"Sittiwangkul","year":"2006","journal-title":"Singapore Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rigante, D., Andreozzi, L., Fastiggi, M., Bracci, B., Natale, M.F., and Esposito, S. (2016). Critical Overview of the Risk Scoring Systems to Predict Non-Responsiveness to Intravenous Immunoglobulin in Kawasaki Syndrome. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030278"},{"key":"ref_29","unstructured":"Kliegman, R., and St Geme, J. (2019). Nelson, Textbook of Pediatrics, Elsevier. [21st ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.echo.2010.10.004","article-title":"New equations and a critical appraisal of coronary artery Z scores in healthy children","volume":"24","author":"Dallaire","year":"2011","journal-title":"J. Am. Soc. Echocardiogr."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/7\/10\/185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:22:33Z","timestamp":1760178153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/7\/10\/185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,16]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["children7100185"],"URL":"https:\/\/doi.org\/10.3390\/children7100185","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,16]]}}}