Therapy For Respiratory Distress Syndrome Research Articles

Abscisic acid for acute respiratory distress syndrome therapy by suppressing alveolar macrophage pyroptosis via upregulating acyloxyacyl hydrolase expression

ObjectiveAbscisic acid (ABA) is a phytohormone that inhibits airway inflammation in acute respiratory distress syndrome (ARDS) mouse models. However, the molecular mechanism underlying this phenomenon remains unclear. Methods: Serum ABA level in patients and mice was measured via liquid chromatography–tandem mass spectrometry (LC–MS/MS). In-depth molecular mechanism was investigated through transmission electron microscopy, RNA-sequencing, and molecular docking in ARDS mice and cultured primary alveolar macrophages (AMs). ResultsWe found that the serum ABA level was remarkably decreased in ARDS mice and patients. ABA inhibited lipopolysaccharide (LPS)-induced airway inflammation in mice; moreover, it downregulated genes associated with pyroptosis, as shown by RNA-sequencing and lung protein immunoblots. ABA inhibited the formation of membrane pores in AMs and suppressed the cleavage of gasdermin D (GSDMD) and the activation of caspase-11 and caspase-1 in vivo and in vitro; however, the overexpression of caspase-11 reversed the protective effect of ABA on LPS-induced pyroptosis of primary AMs. ABA inhibited intra-AM LPS accumulation while increasing the level of acyloxyacyl hydrolase (AOAH) in AMs, whereas AOAH deficiency abrogated the suppressive action of ABA on inflammation, pyroptosis, and intra-AM LPS accumulation in vivo and in vitro. Importantly, ABA promoted its intracellular receptor lanthionine C-like receptor 2 interacting with transcription factor peroxisome proliferator-activated receptor γ, which ultimately leading to increase AOAH expression to inactivate LPS and inhibit pyroptosis in AMs. ConclusionsABA protected against LPS-induced lung injury by inhibiting pyroptosis in AMs via proliferator-activated receptor γ-mediated AOAH expression.

Diagnostic utility of lung ultrasound in predicting the need for surfactant therapy in preterm neonates with respiratory distress.

Lung ultrasound is an accurate and early predictor for surfactant replacement therapy in respiratory distress syndrome (RDS) as compared to clinical parameters and chest x-ray. However, lung pathologies for respiratory distress at birth have overlapping symptomatology and low middle-income countries have a higher incidence of congenital pneumonia, in addition to RDS, making the immediate diagnosis difficult. Thus, there is a need for assessing a cutoff for lung ultrasound scores in the given setting. The primary objective was to determine the diagnostic accuracy of the lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to the fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A), and chest x-ray (CXR) findings. A prospective observational study was carried out at a tertiary-level neonatal intensive care unit in India in 2022 enrolling 100 neonates <34 weeks gestational age with respiratory distress at birth. After initial stabilization of the neonate, LUS was performed and baseline parameters were noted. Surfactant was administered as per the 2019 European Consensus guidelines and LUS was repeated after 6 h of therapy. The mean gestation of enrolled neonates was 31.06 ± 2.12 weeks and the mean birthweight was 1,412 ± 391 g. Approximately 58% were diagnosed with RDS and 30% had congenital pneumonia. Surfactant was administered to 40% of neonates. The cutoff LUS for surfactant therapy was 7 [area under the curve (AUC) 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 92.5%, specificity 96.67%, PPV 94.87%, and NPV 95.08%] and the cutoff LUS for the second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001). The score decreased by 3.24 (2.44-4.05) after 6 h of the first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650), and CXR findings (0.801). The study predicted an optimal LUS cutoff of 7 and 10 for the need for the first dose of surfactant and re-treatment, respectively, in neonates <34 weeks gestational age with respiratory distress.

Comparison of the efficacy of two natural surfactants (BERAKSURF and BLES) in the treatment of respiratory distress syndrome among preterm neonates

BackgroundThe benefit of surfactant replacement therapy for respiratory distress syndrome (RDS) has been demonstrated. However, some surfactants are expensive and usually inaccessible. Consequently, the Iranian Survanta was produced, but its effect on complications and mortality of RDS is unknown. This study aimed to compare the therapeutic outcomes of Iranian surfactant (beraksurf) and BLES (bovine lipid extract surfactant) on RDS treatment among preterm neonates.MethodsThis triple blinded randomized controlled trial study was performed on 128 eligible neonates diagnosed with RDS in Afzalipour hospital in Kerman, Iran. Diagnosis of RDS, gestational age of 28–34 weeks and weight ≥ 1 kg were considered as inclusion criteria. Congenital anomalies such as congenital cyanotic heart diseases, digestive system anomalies and chromosome abnormalities were the exclusion criteria Neonates were randomly assigned into two equal groups: (1) those treated with BLES (n = 64) and (2) those treated with beraksurf (n = 64). Complications including patent ductus arteriosus (PDA), sepsis, intraventricular hemorrhage (IVH), pneumothorax, pulmonary hemorrhage, mortality, and also, the number of days required for invasive mechanical ventilation (using ventilator) and non-invasive continuous positive airway pressure (CPAP) were evaluated for all neonates. The risk ratio (RR) was calculated at 95% of confidence intervals (CI).ResultsCompared with BLES group, the RR estimate among neonates in beraksurf group was 0.89 (0.66–1.20) for PDA, 0.71 (0.23–2.13) for IVH, 0.44 (0.14–1.36) for sepsis, 0.35 (0.13–0.93) for pneumothorax, 0.33 (0.12–0.86) for pulmonary hemorrhage, and 0.55 (0.28–1.05) for mortality.ConclusionsDespite advances in the use of exogenous surfactants for the treatment of neonatal respiratory distress syndrome; There are still some controversial topics in this field. The results obtained in the present study showed that the two types of surfactant (BERAKSURF and BLES) have similar efficacy for the treatment and short-term outcomes in preterm infants with respiratory distress syndrome. Therefore, due to the cost-effectiveness of BRAKSURF compared to BLES, We recommend choosing BERAKSURF in terms of treatment.

Early Surfactant Therapy for Respiratory Distress Syndrome in Very Preterm Infants.

It is currently considered that early initiation of nasal continuous positive airway pressure, using a less invasive exogenous surfactant administration and avoiding mechanical ventilation as much as possible to minimize lung damage, may reduce mortality and/or the risk of morbidities in preterm infants. The aim of our study was to quantify our experience and compare different strategies of surfactant administration, to investigate which method is associated with less morbidity. A total of 135 preterm infants with early rescue surfactant administration for respiratory distress syndrome were included in the study. The infants were treated in an academic, Level III Neonatal Intensive Care Unit over a 3-year period between 1 December 2018 and 1 December 2021. Patients were separated into three groups: those with standard surfactant administration; those with Less Invasive Surfactant Administration-LISA; and those with Intubation Surfactant Administration Extubation-INSURE. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 h, while the secondary outcomes were major neonatal morbidities and death before discharge. The surfactant administration method was significantly associated with the need for mechanical ventilation within 72 h after the procedure (p < 0.001). LISA group infants needed less MV (OR = 0.538, p = 0.019) than INSURE group infants. We found less morbidities (OR = 0.492, p = 0.015) and deaths before discharge (OR = 0.640, p = 0.035) in the LISA group compared with the INSURE group. The analysis of morbidities found in infants who were given the surfactant by the LISA method compared with the INSURE method showed lower incidence of pneumothorax (3.9% vs. 8.8%), intraventricular hemorrhage (17.3% vs. 23.5%), intraventricular hemorrhage grade 3 and 4 (3.9% vs. 5.9%), sepsis/probable sepsis (11.5% vs. 17.7%) retinopathy of prematurity (16.7% vs. 26.7%) and deaths (3.9% vs. 5.9%). There were no significant differences between groups in frequencies of bronchopulmonary dysplasia, necrotizing enterocolitis and patent ductus arteriosus. Less invasive surfactant administration methods seem to have advantages regarding early need for mechanical ventilation, decreasing morbidities and death rate. In our opinion, the LISA procedure may be a good choice in spontaneously breathing infants regardless of gestational age.

Outcome of Surfactant replacement therapy for respiratory distress syndrome in preterm babies

Introduction: Surfactant is an important treatment modality in preterm babies with respiratory distress syndrome leading to decrease in mortality, morbidity and cost of treatment. Experiences on surfactant therapy in Nepal are scarce. This study was conceptualised to find the use and immediate outcome of surfactant therapy in preterm babies in a tertiary care hospital in Nepal. Methods: A cross-sectional study was done in preterm babies who received surfactant over period of five years at neonatal / pediatric intensive care unit at Patan Hospital, Lalitpur, Nepal. After approval from Institutional review committee, information on gestational age, sex, birth weight, doses of dexamethasone, doses and time surfactant delivery, complications and immediate outcome was retrieved from the files. Comparison between early and late rescue group was done. Data was analysed using SPSS 16. Results: Twelve babies (11.2%) needed a repeat dose of surfactant. Only 12 (11.2%) babies received early rescue surfactant. About 53 (49.5%) babies developed complications with hypotension being the most common seen in 38 (35.5%) babies. Complications were 75% and 46% in the early and late rescue group respectively (p - 0.22). The mortality was inversely proportional to the gestational age (p - 0.002) and birth weight (p &lt; 0.05). Mortality was 16% in both the groups but the deaths related to complications of surfactant was all in the late rescue group. Conclusions: Complications were more in early rescue group and mortality was similar in both the groups, but mortality related to complications of surfactant was all in the late rescue group. Complications of surfactant therapy and mortality were inversely proportional to the gestational age and birth weight.

Natural Versus Synthetic Surfactant Therapy in Respiratory Distress Syndrome of Prematurity.

To compare the clinical efficacy and the cost of treatment between the newborns who received either a natural or a protein-free synthetic surfactant for respiratory distress syndrome (RDS) of prematurity. This is a retrospective analytical study incorporating comparisons of clinical parameters and cost in newborns having RDS of prematurity who received either Survanta (bovine lung extract), a natural surfactant or Surfact (protein-free colfosceril palmitate), a synthetic surfactant. There were 100 newborns who received either of the natural (n = 52) or synthetic (n = 48) surfactant with mean (SD) gestational age and mean (SD) birth weight of 31.5 (2.6) wk, 1425 (461) g and 32.2 (2.2) wk, 1519 (413) g, respectively. Majority of the newborns (> 90%) received endotracheal surfactant within the first 24h of life and had similar baseline characteristics in either group. No differences were noted in ventilator settings on admission and 24h after surfactant/admission. Oxygen requirement, extubation age, complications, hospital stay, and mortality were similar across groups, except that the necrotizing enterocolitis was noted only in natural surfactant group. There was a significant pharmacy cost savings in synthetic surfactant group. Synthetic surfactant was comparable to natural surfactant with regard to outcomes, like ventilator settings, hospital stay, and mortality. Pharmacy cost was less in synthetic surfactant group.

Surfactant Therapy for Respiratory Distress Syndrome in High- and Ultra-High-Altitude Settings.

ObjectiveThe objective of this study is to investigate the therapeutic effect of surfactant replacement therapy (SRT) on respiratory distress syndrome (RDS) in premature infants in the Qinghai-Tibet Plateau.Materials and MethodsThis multi-center retrospective cohort study collected and screened reasonable clinical data of 337 premature infants with RDS from 10 hospitals in the Qinghai-Tibet Plateau from 2015 to 2017. We grouped the cases by rationally analyzing their baseline characteristics, using logistic analysis to evaluate each factor's effect on the prognosis of the infants, and comparing the short-term improvement in blood gas and mortality after SRT treatment at different altitudes, in high-altitude (1,500–3,500 m) and ultra-high-altitude (3,500–5,500 m) groups.ResultsIndependent of altitude, the mortality rate of children with RDS in the SRT group was significantly lower than that of children in the non-SRT group (both P < 0.05). The effect of SRT on preterm infants with RDS in the high-altitude group [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.22–0.87, P = 0.02] was better than that in the infants in the ultra-high-altitude group (OR = 0.26, 95% CI = 0.13–0.58, P < 0.01), with death rates of 34.34 and 49.71%, respectively. Similarly, after SRT, the improvement of PaO2/FiO2 and pH of children at high altitude was significantly better than those of children at ultra-high altitude (all P < 0.01).ConclusionsSRT plays a prominent role in curing infants with RDS in both high- and ultra-high-altitude regions, although with better effects at high rather than ultra-high altitude. This study provides a basis for further large-scale studies on SRT for RDS treatment at high altitudes.

Comparison Between Nasal High-Frequency Oscillatory Ventilation And Nasal Continuous Positive Airway Pressure In The Management Of Respiratory Distress Syndrome

Context: A neonatal respiratory distress syndrome occurs at or soon after delivery (<24 hours). Premature newborns with respiratory distress syndrome (RDS) often need breathing assistance. There has been a tendency to reduce in the previous decade the use of non-invasive ventilation modes (NIV) in neonatal intensive care units to prevent ventilator-induced lung damage, in particular after recent data showing NIV in preterm babies has equivalent efficiency compared to EMV. In practical practise, different forms of NIV may be employed include nasal continuing positive airway pressure and noninvasive intermittent positive airway pressure. Nasal continuous positive airway pressure is one of the most often utilised non-invasive techniques (NCPAP). Although HFV has been used in several neonatal critical care units, a relatively novel modality of nasal high frequency oscillatory ventilation (nHFOV) is limited in evidence of its utility. The objective of this research has been to examine the effectiveness and safety of nasal oscillatory ventilation with nasal airway continuous pressure in preterm baby respiratory distress syndrome therapy. Methods: This research is a (60 instances) clinical experiment conducted with respiratory distress syndrome (admitted to the Benha University Hospital Neonatal Intensive Care Unit and Benha Kids Hospital) between the 1–28 day age range. Cases were randomly picked in two groups: Group I: 30 instances of high-frequency oscillatory nasal ventilation were treated (nHFOV). Group II: 30 individuals with constant nasal airway pressure were treated (NCPAP). Methods: Detailed history of medicine. Total usage time NHFV and NCPAP usage time and oxygenation time required for each instance. Complication detection occurs during non-invasive breathing (pulmonary air leak syndrome, IVH, nasal injury and other.) Studies of imagery. Outcomes: There was no statistically significant difference in demographic data between the two groups. There was a statistically significant difference in IVH complication between Group I and Group II. The percentage of nasal septal injuries in Group I was significantly lower than in Group II. The rate of intervention failure (intubing and ventilator demand) in Group I was significantly lower than in Group II (3.3 percent, (26.6 percent) p value=0.030. Conclusion: High frequency nasal ventilation has a greater impact than continuous airway pressure on infants and is less complicated. This research revealed that the length of non-invasive respiratory support was greatly shortened by high frequency nasal ventilation and the necessity for intubation was minimised compared to the continuous positive airway pressure of RDS infants.

Association of Adherence to Surfactant Best Practice Uses With Clinical Outcomes Among Neonates in Sweden

While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework. To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks). This population-based cohort study used registry data for 97 377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020. Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS. In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic corticosteroids for lung disease, treatment with supplemental oxygen at 28 days' postnatal age and at 36 weeks' postmenstrual age. Odds ratios (ORs) were calculated and adjusted for any prenatal corticosteroid treatment, cesarean delivery, GA, infant sex, Apgar score at 10 minutes, and birth weight z score of less than -2. In total, 7980 surfactant administrations were given to 5209 infants (2233 [42.9%] girls; 2976 [57.1%] boys): 629 (12.1%) born at full term, 691 (13.3%) at 32 to 36 weeks' GA, 1544 (29.6%) at 28 to 31 weeks' GA, and 2345 (45.0%) at less than 28 weeks' GA. Overall, 977 infants (18.8%) received off-label use. In 1364 of 3508 infants (38.9%) with GA of 22 to 31 weeks, the first administration of surfactant was given more than 2 hours after birth, and this was associated with higher odds of pneumothorax (adjusted OR [aOR], 2.59; 95% CI, 1.76-3.83), intraventricular hemorrhage grades 3 to 4 (aOR, 1.71; 95% CI, 1.23-2.39), receipt of postnatal corticosteroids (aOR, 1.57; 95% CI, 1.22-2.03), and longer duration of assisted ventilation (aOR, 1.34; 95% CI, 1.04-1.72) but also higher survival (aOR, 1.45; 95% CI, 1.10-1.91) than among infants treated within 2 hours of birth. In 146 infants (2.8%), the recommended maximum of 3 surfactant administrations was exceeded but without associated improvements in outcome. Omission of surfactant treatment occurred in 203 of 3551 infants (5.7%) who were receiving mechanical ventilation and was associated with lower survival (aOR, 0.49; 95% CI, 0.30-0.82). In full-term infants, 336 (53.4%) of those receiving surfactant had a diagnosis of meconium aspiration syndrome. Surfactant for meconium aspiration was not associated with improved neonatal outcomes. In this study, adherence to best practices and labels for surfactant use in newborn infants varied, with important clinical implications for neonatal outcomes.

The efficacy of intra-tracheal budesonide with surfactant in treatment of respiratory distress syndrome and prevention of bronchopulmonary dysplasia

Background: Premature birth is an important issue in developed and developing countries. Surfactant replacement therapy of respiratory distress syndrome (RDS) causes a change in the normal pattern of the disease and increases the likelihood of survival of more premature newborns with chronic pulmonary damage. The purpose of this study was to investigate the effects of budesonide and surfactant on the treatment of respiratory distress syndrome and the prevention of bronchopulmonary dysplasia. Methods: In a randomized clinical trial, 128 preterm infants less than 1250 g or gestational age of 26-30 weeks that were admitted to Al-Zahra Hospital from 2017 to 2018 with RDS and needed surfactant replacement therapy were enrolled. They were randomly allocated into two groups. In one group (group Surfactant), the surfactant was administered intratracheally 2.5 cc/kg and in the second group (group Surfactant + Budesonide), budesonide was administered 0.25 mg/kg in addition to the intratracheal surfactant. The primary outcome was bronchopulmonary dysplasia and the secondary outcome was complications of prematurity. Results: In this study 128 neonates including 48 (60.9%) boys and 50 (39.1%) girls were studied. The mean gestational ages of studied neonates were 28.32±1.60 weeks. The mean duration of mechanical ventilation, continuous positive airway pressure (CPAP), high flow nasal cannulae (HFNC), and need for supplemental oxygen were significantly shorter in the group that received surfactant and budesonide combination. The required FiO2 at four hours after surfactant treatment was significantly lower in group Surfactant + Budesonide than the Surfactant group (p = 0.01). In the group Surfactant, 38 neonates (59.4%) and in group S+B, 24 cases (37.5%) developed bronchopulmonary dysplasia (BPD), (p = 0.04). The mortality rate was 15 neonates that 6 cases were in group S+B (p =0.29). Conclusion: In our study, using surfactant with budesonide combination in comparison with surfactant alone is associated with less respiratory support and BPD rate. Future studies with a larger number of patients before routine use of surfactant and budesonide combination is recommended.

Roxadustat attenuates hyperoxia-induced lung injury by upregulating proangiogenic factors in newborn mice

Premature infants who require oxygen therapy for respiratory distress syndrome often develop bronchopulmonary dysplasia, a chronic lung disease characterized by interrupted alveologenesis. Disrupted angiogenesis inhibits alveologenesis; however, the mechanisms through which disrupted angiogenesis affects lung development are poorly understood. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple oxygen-sensitive genes, including those encoding for vascular endothelial growth factor (VEGF). However, the HIF modulation of angiogenesis in hyperoxia-induced lung injury is not fully understood. Therefore, we explored the effects of roxadustat, an HIF stabilizer that has been shown to promote angiogenesis, in regulating pulmonary angiogenesis on hyperoxia exposure. C57BL6 mice pups reared in room air and 85% O2 were injected with phosphate-buffered saline or 5mg/kg or 10mg/kg roxadustat. Their daily body weight and survival rate were recorded. Their lungs were excised for histology and angiogenic factor expression analyses on postnatal Day 7. Exposure to neonatal hyperoxia reduced body weight; survival rate; and expressions of von Willebrand factor, HIF-1α, phosphor mammalian target of rapamycin, VEGF, and endothelial nitric oxide synthase and increased the mean linear intercept values in the pups. Roxadustat administration reversed these effects. Hyperoxia suppressed pulmonary vascular development and the expression of proangiogenic factors. Roxadustat promoted pulmonary angiogenesis on hyperoxia exposure by stabilizing HIF-1α and upregulating the expression of proangiogenic factors, indicating its potential in clinical and therapeutic applications.

TRIM72 mediates lung epithelial cell death upon hyperoxia exposure.

Premature infants often require oxygen (O2) therapy for respiratory distress syndrome; however, excessive use of O2 can cause clinical conditions such as bronchopulmonary dysplasia. Although many treatment methods are currently available, they are not effective in preventing bronchopulmonary dysplasia. Herein, we explored the role of tripartite motif protein 72 (TRIM72), a factor involved in repairing alveolar epithelial wounds, in regulating alveolar cells upon hyperoxia exposure. In this in vivo study, we used Sprague-Dawley rat pups that were reared in room air or 85% O2 for 2 weeks after birth. The lungs were excised for histological analyses, and TRIM72 expression was assessed on postnatal days 7 and 14. For in vitro experiments, RLE-6TN cells (i.e., rat alveolar type II epithelial cells) and A549 cells (i.e., human lung carcinoma epithelial cells) were exposed to 85% O2 for 5 days. The cells were then analyzed for cell viability, and TRIM72 expression was determined. Exposure to hyperoxia reduced body and lung weight, increased mean linear intercept values, and upregulated TRIM72 expression. In vitro study results revealed increased or decreased lung cell viability upon hyperoxia exposure depending on the suppression or overexpression of TRIM72, respectively. Hyperoxia upregulates TRIM72 expression in neonatal rat lung tissue; moreover, it initiates TRIM72-dependent alveolar epithelial cell death, leading to hyperoxia-induced lung injury.

Safety of Early Rescue Surfactant Replacement Therapy for Preterm Neonates with Respiratory Distress Syndrome at Neonatal Intensive Care Unit of a Tertiary Hospital

Introduction: Respiratory distress syndrome (RDS) is an acute disease of preterm neonates and is caused by the deficiency of pulmonary surfactant. Surfactant deficiency can lead to alveolar collapse, atelectasis, impaired gas exchange, severe hypoxia and acidosis. Surfactant replacement therapy (SRT) is an integral part of management of preterm neonates with respiratory distress syndrome. The objective of the study was to evaluate the safety of early rescue surfactant replacement therapy in RDS.&#x0D; Methods: This was a prospective observational study conducted in a 17 bedded teaching and referral NICU of Eastern Nepal over a period of seven months. All preterm neonates with clinical and radiological features of RDS were enrolled in the study. The safety of early rescue SRT was evaluated by measuring the outcomes: incidence of pulmonary haemorrhage, apnea, hypoxia and cardiac arrest. All data were entered into the worksheet of SPSS software version (19.0) and descriptive statistics including percentages and frequencies was analysed. The level of statistical significance adopted was p-value &lt; 0.05. &#x0D; Results: The survival rate of preterm babies with SRT was 64.7% (22 babies). The incidence / prevalence of pulmonary haemorrhage, apnea, hypoxia, and cardiac arrest during or immediately after SRT was 14.7%, 5.9%, 5.9% and 2.9% respectively. &#x0D; Conclusions: This study suggests that SRT is an effective, safe and feasible intervention in level-3 neonatal units and has the potential to reduce neonatal mortality. The study also emphasises on the fact that SRT should be provided in settings where there is adequate manpower, professional skills and desired infrastructure to administer surfactant.

The influence of the technique of surfactant administration (LISA vs INSURE) on the outcomes of respiratory distress syndrome treatment in preterm infants.

Intratracheal administration of exogenous surfactant is a well-established therapy for respiratory distress syndrome in preterm infants. The two preferred methods for respiratory support in neonates that contribute to limiting the risk of lung damage associated with mechanical ventilation include nCPAP and non-invasive ventilation. The increasing popularity of surfactant administration techniques is due to the fact they reduce the time of mechanical ventilation until this medication is administered. In some cases a short period of mechanical ventilation follows (INSURE: INtubation-SURfactant-Extubation). There are also methods that make it possible to completely avoid intubation and help maintain spontaneous breathing during surfactant administration (LISA: Less Invasive Surfactant Administration, MIST: Minimal Invasive Surfactant Therapy).AimTo analyze treatment outcomes in preterm infants who suffer from respiratory distress syndrome and require exogenous surfactant administration depending on the technique used: LISA vs INSURE.Material and methodsThe present retrospective analysis included 129 infants born at a gestational age of between 24 and 33 weeks who were hospitalized in the Neonatology Department in the years 2014-2016, were administered surfactant and remained on non-invasive ventilation. All the subjects received only proractant alfa. Both study groups: LISA (n=83) and INSURE (n=46) were analyzed in terms of respiratory distress treatment outcomes and the presence of complications of prematurity.ResultsThere were no significant differences in patient characteristics between the two study groups (LISA vs INSURE: mean birth body weight was 1210g vs 1275 g, respectively; mean gestational age at birth was 30 weeks vs 29 6/7 weeks, respectively). The comparison of respiratory support method and FiO2 concentration within the first 72 hours after surfactant administration showed no significant differences between the groups. Similarly, respiratory outcomes did not significantly differ between the LISA and INSURE groups and were: the need for intubation ☒ 42.2% vs 32.6%, p=0.201, duration of mechanical ventilation – median days 0 vs 0, p=0.377, duration of nCPAP – median days 5 vs 5, p=0.379, duration of oxygen supplementation – median days 1 vs 1, p=0.555, and the incidence of bronchopulmonary dysplasia – 28.9% vs 23.9%, p=0.506. Also, the incidence of complications was similar in both study groups.ConclusionsOur retrospective analysis of preliminary outcomes of surfactant administration involving the use of the LISA technique showed no statistically significant differences as compared with the INSURE method. The randomized, prospective study that is currently being conducted at our Neonatology Department and includes biochemical markers of lung damage, will bring more objective data on the safety and effectiveness of both surfactant administration techniques (LISA vs INSURE).

EOLIA trial: the future of extracorporeal membrane oxygenation in acute respiratory distress syndrome therapy?

In the EOLIA trial, early use of ECMO did not significantly improve mortality at 60 days in patients with severe ARDS, but when used as a rescue modality ECMO might help improve survival http://bit.ly/2XOjwSE

Nasal high-frequency oscillatory ventilation (nHFOV) versus nasal continuous positive airway pressure (NCPAP) as an initial therapy for respiratory distress syndrome (RDS) in preterm and near-term infants

BackgroundCurrently, various forms of non-invasive respiratory support have been used in the management of respiratory distress syndrome (RDS) in preterm neonates. However, nasal high-frequency oscillatory ventilation (nHFOV) has not yet...

Comprehensive characterization and proteoform analysis of the hydrophobic surfactant proteins B and C in calf pulmonary surfactant

Calf pulmonary surfactant (CPS), which contains about 98% lipids and 2% hydrophobic surfactant proteins B (SP-B) and C (SP-C), has been used as a surfactant preparation for the clinical replacement therapy of respiratory distress syndrome (RDS). Characterization of SP-B and SP-C in CPS is informative for quality control and the evaluation of their biological activities. However, analysis of SP-B and SP-C is impeded by the high content of lipids in CPS. Here, we describe an integrated method by combining size exclusion chromatography (SEC)–based delipidation, SDS-PAGE separation, in-gel digestion and mass spectrometric analysis for comprehensive characterization and proteoform analysis of the extremely hydrophobic SP-B and SP-C in CPS. This study has shown that 30 proteoforms of SP-C with different truncations and modifications were identified and SP-B was found to be existed as a dimer form in the CPS.

Surfactant Replacement Therapy for Respiratory Distress Syndrome in the Newborn: A Review

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in low birth weight premature infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Exogenous surfactant therapy has become well established in newborn infants with respiratory distress. Many aspects of its use have been well evaluated in high-quality trials and systematic reviews. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/ sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This article summarizes the evidence and gives recommendations for the use of surfactant therapy for respiratory distress syndrome (RDS) in newborn.Bangladesh J Child Health 2016; VOL 40 (1) :26-30

Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future.

Respiratory distress syndrome (RDS) due to surfactant deficiency is the most common cause of respiratory failure in preterm infants. Tremendous progress has been made since the original description that surfactant deficiency is the major cause of RDS. Surfactant therapy has been extensively studied in preterm infants and has been shown to significantly decrease air leaks and neonatal and infant mortality. Synthetic and animal-derived surfactants from bovine as well as porcine origin have been evaluated in randomized controlled trials. Animal-derived surfactants generally result in faster weaning of respiratory support, shorter duration of invasive ventilation, and decreased mortality when compared to first- or second-generation of synthetic surfactants, but some of the second-generation synthetic surfactants are at least not inferior to the animal-derived surfactants. Using a higher initial dose of porcine derived surfactant may provide better outcomes when compared with using lower doses of bovine surfactants, likely, due to compositional difference and/or the dose. Third-generation synthetic surfactant containing peptide analogs of surfactant protein B and C are currently being studied. Less invasive intra-tracheal surfactant administration techniques in spontaneously breathing neonate receiving noninvasive ventilator support are also being evaluated. In the present era, prophylactic surfactant is not recommended as it may increase the risk of lung injury or death. In the future, surfactants may be used as vector to deliver steroids, or used in combination with molecules, such as, recombinant Club Cell Protein-10 (rhCC-10) to improve pulmonary outcomes. Also, noninvasive surfactant administration techniques, such as aerosolization or atomization of surfactant may play a greater role in the future.

Heated, Humidified High-Flow Nasal Cannula vs Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome of Prematurity: A Randomized Clinical Noninferiority Trial.

Heated, humidified high-flow nasal cannula (HHHFNC) has gained increasing popularity as respiratory support for newborn infants thanks to ease of use and improved patient comfort. However, its role as primary therapy for respiratory distress syndrome (RDS) of prematurity needs to be further elucidated by large, randomized clinical trials. To determine whether HHHFNC provides respiratory support noninferior to nasal continuous positive airway pressure (nCPAP) or bilevel nCPAP (BiPAP) as a primary approach to RDS in infants older than 28 weeks' gestational age (GA). An unblinded, monocentric, randomized clinical noninferiority trial at a tertiary neonatal intensive care unit. Inborn infants at 29 weeks 0 days to 36 weeks 6 days of GA were eligible if presenting with mild to moderate RDS requiring noninvasive respiratory support. Criteria for starting noninvasive respiratory support were a Silverman score of 5 or higher or a fraction of inspired oxygen higher than 0.3 for a target saturation of peripheral oxygen of 88% to 93%. Infants were ineligible if they had major congenital anomalies or severe RDS requiring early intubation. Infants were enrolled between January 5, 2012, and June 28, 2014. Randomization to either HHHFNC at 4 to 6 L/min or nCPAP/BiPAP at 4 to 6 cm H2O. Need for mechanical ventilation within 72 hours from the beginning of respiratory support. The absolute risk difference in the primary outcome and its 95% confidence interval were calculated to determine noninferiority (noninferiority margin, 10%). An intention-to-treat analysis was performed. A total of 316 infants were enrolled in the study: 158 in the HHHFNC group (mean [SD] GA, 33.1 [1.9] weeks; 52.5% female) and 158 in the nCPAP/BiPAP group (mean [SD] GA, 33.0 [2.1] weeks; 47.5% female). The use of HHHFNC was noninferior to nCPAP with regard to the primary outcome: failure occurred in 10.8% vs 9.5% of infants, respectively (95% CI of risk difference, -6.0% to 8.6% [within the noninferiority margin]; P = .71). Significant between-group differences in secondary outcomes were not found between the HHHFNC and nCPAP/BiPAP groups, including duration of respiratory support (median [interquartile range], 4.0 [2.0 to 6.0] vs 4.0 [2.0 to 7.0] days; 95% CI of difference in medians, -1.0 to 0.5; P = .45), need for surfactant (44.3% vs 46.2%; 95% CI of risk difference, -9.8 to 13.5; P = .73), air leaks (1.9% vs 2.5%; 95% CI of risk difference, -3.3 to 4.5; P = .70), and bronchopulmonary dysplasia (4.4% vs 5.1%; 95% CI of risk difference, -3.9 to 7.2; P = .79). In this study, HHHFNC showed efficacy and safety similar to those of nCPAP/BiPAP when applied as a primary approach to mild to moderate RDS in preterm infants older than 28 weeks' GA. clinicaltrials.gov Identifier: NCT02570217.