{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:37:52Z","timestamp":1780555072329,"version":"3.54.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2019,11,30]],"date-time":"2019-11-30T00:00:00Z","timestamp":1575072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2019,11,30]],"date-time":"2019-11-30T00:00:00Z","timestamp":1575072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2020,5]]},"DOI":"10.1038\/s41390-019-0696-x","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T10:40:32Z","timestamp":1575283232000},"page":"1019-1024","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A novel delivery system for supraglottic atomization allows increased lung deposition rates of pulmonary surfactant in newborn piglets"],"prefix":"10.1038","volume":"87","author":[{"given":"Anders","family":"Nord","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikard","family":"Linner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Milesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Zannin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"di Castri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele L.","family":"Dellac\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Cunha-Goncalves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Perez-de-Sa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,30]]},"reference":[{"key":"696_CR1","first-page":"278483","volume":"2012","author":"S Gupta","year":"2012","unstructured":"Gupta, S. & Donn, S. M. Novel approaches to surfactant administration. Crit. Care Res. Pract. 2012, 278483 (2012).","journal-title":"Crit. Care Res. Pract."},{"key":"696_CR2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1136\/archdischild-2014-306642","volume":"100","author":"S Sakonidou","year":"2015","unstructured":"Sakonidou, S. & Dhaliwal, J. The management of neonatal respiratory distress syndrome in preterm infants (European Consensus Guidelines-2013 update). Arch. Dis. Child. Educ. Pract. Ed. 100, 257\u2013259 (2015).","journal-title":"Arch. Dis. Child. Educ. Pract. Ed."},{"key":"696_CR3","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1164\/ajrccm\/136.5.1256","volume":"136","author":"A Jobe","year":"1987","unstructured":"Jobe, A. & Ikegami, M. Surfactant for the treatment of respiratory distress syndrome. Am. Rev. Respir. Dis. 136, 1256\u20131275 (1987).","journal-title":"Am. Rev. Respir. Dis."},{"key":"696_CR4","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0140-6736(80)90489-4","volume":"1","author":"T Fujiwara","year":"1980","unstructured":"Fujiwara, T. et al. Artificial surfactant therapy in hyaline-membrane disease. Lancet 1, 55\u201359 (1980).","journal-title":"Lancet"},{"key":"696_CR5","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1007\/s004310050588","volume":"156","author":"JA Schipper","year":"1997","unstructured":"Schipper, J. A., Mohammad, G. I., van Straaten, H. L. & Koppe, J. G. The impact of surfactant replacement therapy on cerebral and systemic circulation and lung function. Eur. J. Pediatr. 156, 224\u2013227 (1997).","journal-title":"Eur. J. Pediatr."},{"key":"696_CR6","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1203\/00006450-199811000-00012","volume":"44","author":"PH Dijk","year":"1998","unstructured":"Dijk, P. H., Heikamp, A. & Oetomo, S. B. Surfactant nebulization versus instillation during high frequency ventilation in surfactant-deficient rabbits. Pediatr. Res. 44, 699 (1998).","journal-title":"Pediatr. Res."},{"key":"696_CR7","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/jp.2012.166","volume":"33","author":"AC Katheria","year":"2013","unstructured":"Katheria, A. C. & Leone, T. A. Changes in hemodynamics after rescue surfactant administration. J. Perinatol. 33, 525\u2013528 (2013).","journal-title":"J. Perinatol."},{"key":"696_CR8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1159\/000121457","volume":"93","author":"K Bohlin","year":"2008","unstructured":"Bohlin, K., Jonsson, B., Gustafsson, A. S. & Blennow, M. Continuous positive airway pressure and surfactant. Neonatology 93, 309\u2013315 (2008).","journal-title":"Neonatology"},{"key":"696_CR9","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/sj.jp.7211754","volume":"27","author":"K Bohlin","year":"2007","unstructured":"Bohlin, K., Gudmundsdottir, T., Katz-Salamon, M., Jonsson, B. & Blennow, M. Implementation of surfactant treatment during continuous positive airway pressure. J. Perinatol. 27, 422\u2013427 (2007).","journal-title":"J. Perinatol."},{"key":"696_CR10","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/S0140-6736(11)60986-0","volume":"378","author":"W G\u00f6pel","year":"2011","unstructured":"G\u00f6pel, W. et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 378, 1627\u20131634 (2011).","journal-title":"Lancet"},{"key":"696_CR11","doi-asserted-by":"crossref","unstructured":"Kanmaz, H. G. et al. Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics 131, e502\u2013e509 (2013).","DOI":"10.1542\/peds.2012-0603"},{"key":"696_CR12","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/apa.12883","volume":"104","author":"W Gopel","year":"2015","unstructured":"Gopel, W. et al. Less invasive surfactant administration is associated with improved pulmonary outcomes in spontaneously breathing preterm infants. Acta Paediatr. 104, 241\u2013246 (2015).","journal-title":"Acta Paediatr."},{"key":"696_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26437-x","volume":"8","author":"C Hartel","year":"2018","unstructured":"Hartel, C. et al. Less invasive surfactant administration and complications of preterm birth. Sci. Rep. 8, 8333 (2018).","journal-title":"Sci. Rep."},{"key":"696_CR14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1159\/000369955","volume":"107","author":"R Linner","year":"2015","unstructured":"Linner, R., Perez-de-Sa, V. & Cunha-Goncalves, D. Lung deposition of nebulized surfactant in newborn piglets. Neonatology 107, 277\u2013282 (2015).","journal-title":"Neonatology"},{"key":"696_CR15","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00431-010-1292-6","volume":"170","author":"J Mazela","year":"2011","unstructured":"Mazela, J. & Polin, R. A. Aerosol delivery to ventilated newborn infants: historical challenges and new directions. Eur. J. Pediatr. 170, 433\u2013444 (2011).","journal-title":"Eur. J. Pediatr."},{"key":"696_CR16","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/pr.2016.39","volume":"80","author":"I Milesi","year":"2016","unstructured":"Milesi, I. et al. Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome. Pediatr. Res. 80, 92\u2013100 (2016).","journal-title":"Pediatr. Res."},{"key":"696_CR17","unstructured":"Dellac\u00e1, R. F. & Milesi, I. Method and system for the administration of a pulmonary surfactant by atomization. European patents 2012016523420120423 and WO2013160129 A1 (patent pending) (2013)."},{"key":"696_CR18","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1007\/s001340050458","volume":"23","author":"PH Dijk","year":"1997","unstructured":"Dijk, P. H., Heikamp, A. & Bambang Oetomo, S. Surfactant nebulisation: lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits. Intensive Care Med. 23, 1070\u20131076 (1997).","journal-title":"Intensive Care Med."},{"key":"696_CR19","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/S0925-4439(98)00080-5","volume":"1408","author":"B Robertson","year":"1998","unstructured":"Robertson, B. & Halliday, H. L. Principles of surfactant replacement. Biochim. Biophys. Acta 1408, 346\u2013361 (1998).","journal-title":"Biochim. Biophys. Acta"},{"key":"696_CR20","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.reprotox.2012.05.089","volume":"34","author":"DK Rahmel","year":"2012","unstructured":"Rahmel, D. K. et al. The non-intubated, spontaneously breathing, continuous positive airway pressure (CPAP) ventilated pre-term lamb: a unique animal model. Reprod. Toxicol. 34, 204\u2013215 (2012).","journal-title":"Reprod. Toxicol."},{"key":"696_CR21","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.1097\/00003246-200007000-00058","volume":"28","author":"MH Wagner","year":"2000","unstructured":"Wagner, M. H. et al. Endotracheal surfactant atomization: an alternative to bolus instillation? Crit. Care Med. 28, 2540\u20132544 (2000).","journal-title":"Crit. Care Med."},{"key":"696_CR22","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1097\/PCC.0000000000001267","volume":"18","author":"I Milesi","year":"2017","unstructured":"Milesi, I. et al. Supraglottic atomization of surfactant in spontaneously breathing lambs receiving continuous positive airway pressure. Pediatr. Crit. Care Med. 18, e428\u2013e434 (2017).","journal-title":"Pediatr. Crit. Care Med."},{"key":"696_CR23","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1089\/jamp.2007.0663","volume":"21","author":"R Dhand","year":"2008","unstructured":"Dhand, R. Aerosol delivery during mechanical ventilation: from basic techniques to new devices. J. Aerosol Med. Pulm. Drug Deliv. 21, 45\u201360 (2008).","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"696_CR24","unstructured":"Darquenne, C. in The ISAM Textbook of Aerosol Medicine (ed. Dhand, R.) Ch. 2.2 (Mary Ann Libert Publishing, Inc., Rochelle, NY., 2015)."},{"key":"696_CR25","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1203\/00006450-199704000-00006","volume":"41","author":"A Moen","year":"1997","unstructured":"Moen, A., Yu, X. Q., Rootwelt, T. & Saugstad, O. D. Acute effects on systemic and pulmonary hemodynamics of intratracheal instillation of porcine surfactant or saline in surfactant-depleted newborn piglets. Pediatr. Res. 41, 486\u2013492 (1997).","journal-title":"Pediatr. Res."},{"key":"696_CR26","first-page":"869","volume":"1991","author":"JF Lewis","year":"1985","unstructured":"Lewis, J. F., Ikegami, M., Jobe, A. H. & Tabor, B. Aerosolized surfactant treatment of preterm lambs. J. Appl. Physiol. 1991, 869\u2013876 (1985).","journal-title":"J. Appl. Physiol."},{"key":"696_CR27","first-page":"1270","volume":"1991","author":"J Lewis","year":"1985","unstructured":"Lewis, J., Ikegami, M., Higuchi, R., Jobe, A. & Absolom, D. Nebulized vs. instilled exogenous surfactant in an adult lung injury model. J. Appl. Physiol. 1991, 1270\u20131276 (1985).","journal-title":"J. Appl. Physiol."},{"key":"696_CR28","first-page":"1256","volume":"1993","author":"JF Lewis","year":"1985","unstructured":"Lewis, J. F. et al. Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant. J. Appl. Physiol. 1993, 1256\u20131264 (1985).","journal-title":"J. Appl. Physiol."},{"key":"696_CR29","doi-asserted-by":"publisher","first-page":"F3","DOI":"10.1136\/fn.78.1.F3","volume":"78","author":"TF Fok","year":"1998","unstructured":"Fok, T. F., al-Essa, M., Dolovich, M., Rasid, F. & Kirpalani, H. Nebulisation of surfactants in an animal model of neonatal respiratory distress. Arch. Dis. Child. Fetal Neonatal Ed. 78, F3\u2013F9 (1998).","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"696_CR30","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/pr.2013.24","volume":"73","author":"C Rey-Santano","year":"2013","unstructured":"Rey-Santano, C. et al. Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome. Pediatr. Res. 73, 639\u2013646 (2013).","journal-title":"Pediatr. Res."},{"key":"696_CR31","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/pr.2015.165","volume":"78","author":"MC Hutten","year":"2015","unstructured":"Hutten, M. C. et al. Nebulization of Poractant alfa via a vibrating membrane nebulizer in spontaneously breathing preterm lambs with binasal continuous positive pressure ventilation. Pediatr. Res. 78, 664\u2013669 (2015).","journal-title":"Pediatr. Res."},{"key":"696_CR32","doi-asserted-by":"publisher","unstructured":"Gregory, T. J., Irshad, H., Chand, R. & Kuehl, P. J. Deposition of aerosolized lucinactant in nonhuman primates. J. Aerosol Med. Pulm. Drug Deliv. https:\/\/doi.org\/10.1089\/jamp.2018.1505 (2019).","DOI":"10.1089\/jamp.2018.1505"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0696-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0696-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0696-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:37:10Z","timestamp":1744177030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0696-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,30]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["696"],"URL":"https:\/\/doi.org\/10.1038\/s41390-019-0696-x","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,30]]},"assertion":[{"value":"3 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Chiesi Farmaceutici SpA, and Politecnico di Milano University, the home institution of I.M., E.Z., and R.L.D., own patents on the atomization of surfactant licensed to Chiesi Farmaceutici. The authors disclose off-label product use of surfactant where it is delivered by a different route of administration, an investigational device for the delivery of aerosol drugs, though indication (Respiratory Distress Syndrome, RDS) and dosage (200\u2009mg\u2009kg\u22121) have not been changed. Not related to this study, Politecnico di Milano University, home institution of R.L.D., I.M., and E.Z., received research funding from Chiesi Farmaceutici SpA, ACUTRONIC Medical Systems AG, RESTECH Srl, and Philips AB. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}