{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:14:30Z","timestamp":1771488870920,"version":"3.50.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019004","name":"Deanship of Research, Jordan University of Science and Technology","doi-asserted-by":"publisher","award":["20180020"],"award-info":[{"award-number":["20180020"]}],"id":[{"id":"10.13039\/501100019004","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Objective monitoring of improvement during treatment of pulmonary exacerbation can be difficulty in children when pulmonary function testing cannot be obtained. Thus, the identification of predictive biomarkers to determine the efficacy of drug treatments is of high priority. The major aim of the current study was to investigate the serum levels of vasoactive intestinal peptide (VIP) and alpha calcitonin gene related peptide (aCGRP) of cystic fibrosis pediatric patients during pulmonary exacerbation and post-antibiotic therapy, and possible associations of their levels with different clinicopathological parameters.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>21 patients with cystic fibrosis were recruited at onset of pulmonary exacerbation. Serum was collected at time of admission, three days post-antibiotic therapy, and two weeks post-antibiotic therapy (end of antibiotic therapy). Serum VIP and aCGRP levels were measured using ELISA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Overall least square means of serum aCGRP level but not VIP changed from time of exacerbation to completion of antibiotic therapy (p = 0.005). Serum VIP was significantly associated with the presence of diabetes mellitus (p = 0.026) and other comorbidities (p = 0.013), and with type of antibiotic therapy (p = 0.019). Serum aCGRP level was significantly associated with type of antibiotic therapy (p = 0.012) and positive <jats:italic>Staphylococcus aureus<\/jats:italic> microbiology test (p = 0.046).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study could only show significant changes in serum aCGRP levels following treatment of pulmonary exacerbations. Future studies with larger sample size are required to investigate the clinical importance of VIP and aCGRP in cystic fibrosis patients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0284511","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T17:26:52Z","timestamp":1683307612000},"page":"e0284511","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of serum VIP and aCGRP during pulmonary exacerbation in cystic fibrosis: A longitudinal pilot study of patients undergoing antibiotic therapy"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-4966","authenticated-orcid":true,"given":"Maha 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Al-Keilani","year":"2021","journal-title":"Neurological Sciences"},{"issue":"5","key":"pone.0284511.ref033","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/JLB.5COVA1121-626R","article-title":"VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells","volume":"111","author":"JR Temerozo","year":"2022","journal-title":"Journal of Leukocyte Biology"},{"key":"pone.0284511.ref034","article-title":"Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes","volume":"13","author":"X Hou","year":"2022","journal-title":"Frontiers in Endocrinology"},{"key":"pone.0284511.ref035","unstructured":"Sanlioglu AD, Karacay B, Balci MK, Griffith TS, Sanlioglu S, editors. Potential Therapeutic Role of Vasoactive Intestinal Peptide in Diabetes. HUMAN GENE THERAPY; 2012: MARY ANN LIEBERT INC 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA."},{"key":"pone.0284511.ref036","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00570545","article-title":"Vasoactive intestinal polypeptide increases whole pancreatic blood flow but does not affect islet blood flow in the rat","volume":"31","author":"L. 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