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This study investigated whether exogenous surfactant (Alveofact) combined with intratracheal budesonide modulates these pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty preterm neonates with RDS were randomized into four groups to receive Alveofact 50\u2009mg\/kg or 100\u2009mg\/kg, with or without budesonide 0.25\u2009mg\/kg. Tracheal aspirates (TA) and blood samples were obtained at baseline and 24\u2009h post-treatment, and an additional blood sample was obtained at 48\u2009hours. NETs were measured by ELISA, oxidative stress by malondialdehyde (MDA) assay, and PAD4 expression by qPCR. Clinical outcomes, including hospital stay and mortality, were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combination of Alveofact 100\u2009mg\/kg with budesonide significantly reduced NETs and secretory Immunoglobin A (sIgA) in TA, plasma NETs, MDA, and PAD4 expression compared with other treatment groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Plasma and TA NETs levels were strongly correlated across time points. No significant differences were observed in hospital stay, mortality, or complications among groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A combination of 100\u2009mg\/kg Alveofact with budesonide effectively attenuates neutrophil-driven inflammation and oxidative stress in neonatal RDS. The study was registered on the Clinical Trial Registration Site (ID: NCT06367881, first submitted 2024-04-07).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/study\/NCT06367881?term=NCT06367881&amp;rank=1\" ext-link-type=\"uri\">https:\/\/www.clinicaltrials.gov\/study\/NCT06367881?term=NCT06367881&amp;rank=1<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>High-dose Alveofact + budesonide lowers NETs, PAD4, and oxidative stress.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma NETs strongly correlate with normalized tracheal aspirates NETs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>First trial to test surfactant\u2013steroid effects on neutrophil pathways in RDS.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Therapy reduces neutrophil-mediated inflammation in preterm neonates.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma NETs may serve as a minimally invasive biomarker for RDS monitoring.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-04824-9","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:05:18Z","timestamp":1774263918000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-dependent effects of Alveofact with and without steroids on neutrophil extracellular traps in neonatal respiratory distress syndrome"],"prefix":"10.1038","author":[{"given":"Amira M.","family":"Rashad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nashwa","family":"El-Khazragy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisham","family":"Awad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada Ibrahim","family":"Gad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Rabie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"4824_CR1","first-page":"12","volume":"44","author":"J Dyer","year":"2019","unstructured":"Dyer, J. 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