{"doi":"10.1111/apa.15807","title":"EBNEO Review: aerosolised Calfactant in infants with RDS: A feasible route of surfactant administration?","abstract":"EBNEO commentaries on manuscripts relevant to evidence-based neonatal practice are welcomed and published after a formal peer-review process. To learn more, visit <https://ebneo.org/author-instructions/> and contact Dr. Amy Keir (amy.keir@adelaide.edu.au) or Dr. Clyde J. Wright (clyde.wright@cuanschutz.edu) with questions. Although almost 60 years have passed since the initial report of treating RDS with aerosolised surfactant,1 clinicians remain without an effective delivery system. A truly non-invasive approach of surfactant delivery could decrease many of the risks of exposure to mechanical ventilation, including lung injury and bronchopulmonary dysplasia.2-7 Recently, Cummings et al reported the largest RCT (with 457 neonates randomised) to date comparing nebulised surfactant to standard therapy for babies with RDS.8 In this pragmatic clinical trial, administration of nebulised surfactant was shown to reduce the need for liquid surfactant treatment, cutting rates of intubation in half (from ~50% to ~25%), with a number needed to treat of 5 to prevent one intubation. These promising results demonstrate that the modified nebuliser with pacifier interface could effectively and safely administer surfactant to neonates with signs of RDS. Of note, respiratory support at days 3, 7 and 28 did not differ among both groups. In this study, the authors have taken advantage of a ‘pragmatic’ study design. Specifically, the trial did not include criteria dictating intubation and liquid surfactant administration following randomisation. This allowed clinicians—rather than study protocols—to decide who received liquid surfactant following randomisation. There are multiple benefits to this pragmatic design. It could be argued that by incorporating natural variations in clinical practice the study findings would be more likely to be replicated when applied to real-life clinical practice. Additionally, the authors state that by leaving the decision of who to treat with liquid surfactant to the practitioner results in ethically compliant practice. In addition to these benefits, there are potential limitations to this practical design. By not strictly ‘treatment failure’ or ‘surfactant therapy criteria’, the unblinded design could have introduced variability in practice and contributed to differences in outcomes found between treatment arms. Clinicians could have been biased to anticipate a beneficial effect of aerosolised surfactant—this bias potentially resulting in a delay in treatment with liquid surfactant in infants allocated to the aerosol group. This could have manifested as differences between groups in the level of non-invasive respiratory support and oxygen requirement at the time of liquid surfactant administration; however, these data are not available. Of note, treatment with liquid surfactant occurred later in the group following aerosolised surfactant (~24 h) when compared to standard therapy (~10 h), indicating a delay in treatment. Whether this delay and other potential differences have clinical implications is unknown and should be addressed in future trials. This trial constitutes another important step forward in the management of RDS. A truly non-invasive surfactant administration would have broad application and wide-ranging benefits.2 Specifically, trials targeting less mature neonates at very high risk of injury following intubation and mechanical ventilation are eagerly anticipated. By demonstrating safety and feasibility, this trial sets the stage for a more intensive investigation of aerosolised surfactant to treat RDS. https://ebneo.org/aerosolized-calfactant-rds None.","journal":"Acta Paediatrica","year":2021,"id":211698,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":404974,"name":"Clyde J. Wright","orcid":"0000-0002-8449-5631","position":1,"is_corresponding":false},{"id":415315,"name":"Kirsten Glaser","orcid":"0000-0002-2158-0222","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-18T23:52:20.112538Z","pmid":"33682175","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}