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Surfactant proteins A (SP-A) and D (SP-D) are soluble innate immune molecules which maintain lung homeostasis through their dual roles as anti-infectious and immunomodulatory agents. SP-A and SP-D bind numerous viruses including influenza A virus, respiratory syncytial virus (RSV) and human immunodeficiency virus (HIV), enhancing their clearance from mucosal points of entry and modulating the inflammatory response. They also have diverse roles in mediating innate and adaptive cell functions and in clearing apoptotic cells, allergens and other noxious particles. Here, we review how the properties of these first line defense molecules modulate inflammatory responses, as well as host-mediated immunopathology in response to viral infections. Since SP-A and SP-D are known to offer protection from viral and other infections, if their levels are decreased in some disease states as they are in severe asthma and chronic obstructive pulmonary disease (COPD), this may confer an increased risk of viral infection and exacerbations of disease. Recombinant molecules of SP-A and SP-D could be useful in both blocking respiratory viral infection while also modulating the immune system to prevent excessive inflammatory responses seen in, for example, RSV or coronavirus disease 2019 (COVID-19). Recombinant SP-A and SP-D could have therapeutic potential in neutralizing both current and future strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus as well as modulating the inflammation-mediated pathology associated with COVID-19. A recombinant fragment of human (rfh)SP-D has recently been shown to neutralize SARS-CoV-2. Further work investigating the potential therapeutic role of SP-A and SP-D in COVID-19 and other infectious and inflammatory diseases is indicated.

ObjectiveTo evaluate if nebulised surfactant reduces intubation requirement in preterm infants with respiratory distress treated with nasal continuous positive airway pressure (nCPAP).DesignDouble blind, parallel, stratified, randomised control trial.SettingSole tertiary neonatal unit in West Australia.PatientsPreterm infants (290–336 weeks’ gestational age, GA) less than 4 hours of age requiring 22%–30% supplemental oxygen, with informed parental written consent.InterventionsInfants were randomised within strata (290–316 and 320–336 weeks’ GA) to bubble nCPAP or bubble nCPAP and nebulised surfactant (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation (100 mg/kg) was repeated after 12 hours for persistent supplemental oxygen requirement.Main outcome measuresThe primary outcomes were requirement for intubation and duration of mechanical ventilation at 72 hours. Data analysis followed the intention-to-treat principle.Results360 of 606 assessed infants were eligible; 64 of 360 infants were enrolled and randomised (n=32/group). Surfactant nebulisation reduced the requirement for intubation within 72 hours: 11 of 32 infants were intubated after continuous positive airway pressure (CPAP) and nebulised surfactant compared with 22 of 32 infants receiving CPAP alone (relative risk (95% CI)=0.526 (0.292 to 0.950)). The reduced requirement for intubation was limited to the 320–336 weeks’ GA stratum. The median (range) duration of ventilation in the first 72 hours was not different between the intervention (0 (0–62) hours) and control (9 (0–64) hours; p=0.220) groups. There were no major adverse events.ConclusionsEarly postnatal nebulised surfactant may reduce the need for intubation in the first 3 days of life compared with nCPAP alone in infants born at 290–336 weeks’ GA with mild respiratory distress syndrome. Confirmation requires further adequately powered studies.Trial registration numberACTRN12610000857000.

Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).

Background Surfactant decreases surface tension in the peripheral airways and plays a role in regulating the lung’s immune responses. Several reports have documented changes in surfactant proteins levels, especially surfactant protein D (SP-D) and surfactant protein A (SP-A), suggesting their potential as biomarkers for asthma. However, the results of these studies are controversial. This systematic review was done to assess the levels of surfactant proteins in asthmatic patients compared to healthy individuals. Methods A systematic review was conducted according to PRISMA guidelines. Searches were performed in the Medline/PubMed, Web of Science, Embase, and ScienceDirect databases to identify studies that assessed surfactants proteins levels in asthmatic patients. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using R version 4.4.3 meta package. Results A total of 16 studies met the inclusion criteria and were thus considered for this systematic review. Among these, SP-D was the most frequently studied protein in relation to asthma, asthma severity, and lung function parameters in asthmatic patients. Serum and sputum levels of SP-D in asthmatic patients were slightly elevated compared to non-asthmatic individuals. However, these differences were not statistically significant; the pooled SMDs were 0.27 (95% CI: -0.034 to 0.574, P  = 0.082) for serum levels and 1.47 (95% CI, -0.197 to 3.103, P  = 0.084) for sputum levels. Similarly, no significant difference was detected for the analysis of serum SP-A levels, with SMD = 0.18 (95% CI, -0.505 to 0.866, P  = 0.606). Though, some of the reviewed studies showed an association between SP-D levels and disease severity in asthmatic patients. Conclusion Although alterations have been observed in asthma and proposed as biomarkers, this systematic review did not find significant differences in the levels between asthmatics and healthy individuals. However, some studies have suggested an association between SP-D levels and asthma severity. Given the limited number of studies investigating this association, further research is needed to validate the clinical relevance of correlation between SP-D levels and asthma severity.

The acute respiratory distress syndrome (ARDS) results from a deficiency of functional surfactant in the airways. These investigators carried out a multicenter study in which patients with ARDS were treated with a recombinant human surfactant protein C–based surfactant. No clinical benefits were noted. A multicenter study in which patients with ARDS were treated with a recombinant human surfactant protein C–based surfactant. Although exogenous surfactant is of proven benefit in the prevention and treatment of the respiratory distress syndrome in infants, 1 its value in treating patients with the acute respiratory distress syndrome (ARDS) has not been established. Whereas infants with an immature lung have a deficit in surfactant production, patients with ARDS have decreased surfactant production as well as biochemical alterations of endogenous surfactant that impair surface-tension–lowering properties and decreased surfactant function in distal airways. 2 Normally, pulmonary surfactant phospholipids, acting in concert with surfactant proteins A, B, and C, cause alveolar surface tension to reach very low values at end expiration, thus . . .

Pathogenic variants in surfactant proteins SP-B and SP-C cause surfactant deficiency and interstitial lung disease. Surfactant proteins are synthesized as precursors (proSP-B, proSP-C), trafficked, and processed via a vesicular-regulated secretion pathway; however, control of vesicular trafficking events is not fully understood. Through the Undiagnosed Diseases Network, we evaluated a child with interstitial lung disease suggestive of surfactant deficiency. Variants in known surfactant dysfunction disorder genes were not found in trio exome sequencing. Instead, a de novo heterozygous variant in RAB5B was identified in the Ras/Rab GTPases family nucleotide binding domain, p.Asp136His. Functional studies were performed in Caenorhabditis elegans by knocking the proband variant into the conserved position (Asp135) of the ortholog, rab-5. Genetic analysis demonstrated that rab-5[Asp135His] is damaging, producing a strong dominant negative gene product. rab-5[Asp135His] heterozygotes were also defective in endocytosis and early endosome (EE) fusion. Immunostaining studies of the proband’s lung biopsy revealed that RAB5B and EE marker EEA1 were significantly reduced in alveolar type II cells and that mature SP-B and SP-C were significantly reduced, while proSP-B and proSP-C were normal. Furthermore, staining normal lung showed colocalization of RAB5B and EEA1 with proSP-B and proSP-C. These findings indicate that dominant negative–acting RAB5B Asp136His and EE dysfunction cause a defect in processing/trafficking to produce mature SP-B and SP-C, resulting in interstitial lung disease, and that RAB5B and EEs normally function in the surfactant secretion pathway. Together, the data suggest a noncanonical function for RAB5B and identify RAB5B p.Asp136His as a genetic mechanism for a surfactant dysfunction disorder.

Preterm neonates with respiratory distress syndrome (RDS) are commonly treated with surfactant by intubate surfactant extubate (InSurE) technique. Mode of surfactant administration has evolved towards less invasive technique in the last few years. We randomised 58 preterm infants of 28–34 weeks of gestation with RDS within 6 h of birth to receive surfactant by InSurE or minimally invasive surfactant therapy (MIST). Non-invasive positive pressure ventilation (NIPPV) was used as primary respiratory support. The main objective was to compare the need of invasive mechanical ventilation (IMV) in first 72 h of life and secondarily hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular haemorrhage (IVH) (> grade 2), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. We did not find any difference in need of IMV in first 72 h between MIST and InSurE (relative risk with MIST, 0.62; 95% confidence interval, 0.22 to 1.32). No difference was observed in terms of hs PDA, IVH (> grade 2), BPD and composite outcome of BPD/mortality.Conclusion: There is no difference between MIST and InSurE in preterm neonates with RDS with NIPPV as a primary mode of respiratory support. Larger multicentre studies are needed to further explore differences in treatment failure and other secondary outcomes.Trial registration: www.ctri.nic.in id CTRI/2019/03/017992, registration date March 8, 2019.What is Known• InSurE is commonly used for many years for treatment of RDS in preterm neonates.• MIST has been introduced as a newer tool.What is New• MIST with feeding tube is comparable with InSurE in preterm infants with RDS in developing countries.•NIPPV can be used as primary respiratory support for MIST.

Background The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb. Methods Twelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200 mg/kg) and 5 lambs were managed with mechanical ventilation for 120 min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH 2 O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant. Results Surfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance ( p  < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. Conclusions Applying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.

Background. Enterobacter cloacae complex producing extended-spectrum beta-lactamase - ESBL (ECCOE) is a group of gram-negative pathogens responsible for nosocomial outbreaks in vulnerable patients, among whom neonatal patients represent one of the highest risk groups. Methods. We present data from an ECCOE outbreak identified at the Cremona hospital in January 2024, when a case of ECCOE bacteremia was diagnosed in patient admitted to the Neonatology ward. Following the identification of the index case, an infection prevention and control (IPC) program was implemented, based on: isolation of all positive patients with contact precautions, weekly screening of all hospitalized patients, environmental sampling, a program to improve adherence to hand hygiene, enhanced disinfection procedures, and regular data feedback to the ward staff. Results. The retrospective analysis identified a second infection in January 2024. In 2023, no clinical cases were identified and only one positivity for ECCOE emerged from 301 microbiological screening swabs (0.3%). The prospective analysis did not reveal other infections in the following 11 months. Patient surveillance through swabs showed a baseline prevalence of ECCOE of 15.4% in January, which rose to 30.8% in February, significantly decreased in March, then increased again to 38.5% in June and finally dropped to zero in August. The environmental sampling highlighted only one positivity out of 79 samples (1.3% of the samples). The consumption of alcohol hand rub solution, very low at the start of the outbreak (26 L/1,000 patient days - PD), increased to 113 L/1,000 PD, and then decreased by 70% after the outbreak ended. Conclusions. A rapid and complex IPC intervention focusing on improving hand hygiene can help control an ECCOE outbreak in neonatology. However, maintaining adequate adherence to hand hygiene over time remains very challenging.