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American Journal of Perinatology Oct 2022Laryngeal mask airway (LMA) has emerged as an alternative surfactant delivery method. The effectiveness of this method for the delivery of surfactant is uncertain. A... (Meta-Analysis)
Meta-Analysis
Laryngeal Mask Airway for Surfactant Administration Versus Standard Treatment Methods in Preterm Neonates with Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.
OBJECTIVE
Laryngeal mask airway (LMA) has emerged as an alternative surfactant delivery method. The effectiveness of this method for the delivery of surfactant is uncertain. A meta-analysis of randomized control trials (RCTs) comparing LMA with standard methods of surfactant delivery for the outcomes of surfactant dose repetition, oxygen requirement, mechanical ventilation, intubation, mortality, bronchopulmonary dysplasia (BPD), and pneumothorax.
STUDY DESIGN
Systematic review and meta-analysis of RCTs. Homogeneity between studies was analyzed by using I statistics. Risk ratio or mean difference of outcomes was assessed from random effects models. Subgroup analyses were conducted when necessary. Data sources are as follows: Ovid Medline, Embase, and the Cochrane Central Register of Controlled trials from inception till December 2018, bibliographies of identified reviews and trial registries for ongoing studies. RCTs comparing short-term respiratory outcomes in neonates with respiratory distress syndrome who were administered surfactant through an LMA versus standard method of care.
RESULTS
Six RCTs were identified, enrolling a total of 357 infants. Administering surfactant via LMA was associated with decreased FiO requirement (mean difference = 1.82 (95% confidence interval [CI]: -6.01-9.66), decreased intubation (risk ratio [RR] = 0.17; 95% CI: 0.05-0.57), and decreased mechanical ventilation (RR = 0.44; 95% CI: 0.31-0.61). There were no significant differences between groups for death, BPD, or pneumothorax.
CONCLUSION
LMA might be an effective alternative method of surfactant delivery; however, further high-quality RCTs with larger sample size and including extreme preterm infants are needed to establish LMA as an alternative technique for surfactant delivery.
KEY POINTS
· Pulmonary surfactants reduce mortality and pulmonary air leaks in newborns with respiratory distress syndrome.. · Preterm lungs are at risk of volutrauma by mechanical ventilation; laryngoscopy is still traumatic.. · Surfactant administration via LMA to avoid mechanical ventilation and intubation might be feasible..
Topics: Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Laryngeal Masks; Oxygen; Pneumothorax; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 33517565
DOI: 10.1055/s-0041-1722953 -
Chemosphere Jun 2021Air particulate matter (PM) pollution is associated with the alterations in circulating pulmonary damage proteins. But there are not consistent results among the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Air particulate matter (PM) pollution is associated with the alterations in circulating pulmonary damage proteins. But there are not consistent results among the epidemiological studies. The aim of this study is to investigate the alteration of surfactant protein (SP) from PM exposure.
METHODS
We conducted a comprehensive meta-analysis by searching the databases of PubMed, Medline, EMBASE, Web of Science and CNKI before October 2020 which reported PM pollutants and surfactant protein in the population. The sources of heterogeneity were assessed by subgroup (smoking, particulate matter with different aerodynamic diameter, exposure duration) analysis. We also used the publication bias tests for the comprehensive assessment.
RESULTS
This meta-analysis consisted of 10 studies with 1985 subjects. The results showed that the combined standardized mean difference (SMD) value was 0.05, 95% confidence interval (CI) was -0.07 to 0.17 for serum SP-A and -0.81 (95% CI: -1.41 to -0.21) for circulating SP-D. Among smokers, the combined SMD value of SP-A were 0.29 (95% CI: 0.05 to 0.52). We did not find the correlation between publication year of SP-A and SP-D and study heterogeneity.
CONCLUSIONS
Circulating SP-D was significantly decreased by air particulate matter. Serum SP-A was significantly increased by PM exposure among smokers. Circulating surfactant protein may be considered as a biomarker for respiratory injury caused by air particulate matter.
Topics: Air Pollutants; Air Pollution; Environmental Exposure; Humans; Particulate Matter; Surface-Active Agents
PubMed: 33476792
DOI: 10.1016/j.chemosphere.2021.129564 -
Medicine Nov 2020Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated the role of nebulized versus invasively delivered PS, yet the results remained inconsistent. Therefore, we aimed to conduct this meta-analysis to evaluate the effects and safety of nebulized versus invasively delivered PS in the treatment of NRDS.
METHODS
We searched PubMed et al databases from inception date to May 15, 2020 for RCTs that compared nebulized vs invasively delivered PS. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated for each outcome by means of fixed- or random-effects model.
RESULTS
Two RCTs with a total of 95 preterm neonates were identified, with 48 neonates received PS nebulization and 47 neonates undergone invasive PS administration. There was no significant difference in the SpO2 level (MD = -0.44, 95% CI -6.01 to 5.12) and the A/APaO2 level (MD = 0.01, 95% CI -0.02 to 0.05) 1 hour after treatment among 2 groups. But the duration of mechanical ventilation in the nebulization groups was significantly less than that of invasive group (MD = -30.70, 95% CI -41.45 to 19.95).
CONCLUSIONS
Given the limited evidences, the effects and safety of nebulized versus invasively delivered PS still need further verification.
Topics: Administration, Inhalation; Humans; Infant, Newborn; Infusions, Intravenous; Nebulizers and Vaporizers; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 33235071
DOI: 10.1097/MD.0000000000023113 -
Neonatology 2021Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the...
INTRODUCTION
Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the risk of bronchopulmonary dysplasia. Continuous positive airway pressure (CPAP), a form of noninvasive ventilation, is commonly used in modern neonatology. Limited clinical data are available on the acute and long-term effect of neonatal exposure to CPAP on the lung. Given the restricted clinical data, newborn animal models have been used to study the influence of CPAP on lung structure and function. The findings of animal studies can guide neonatal care and improve the use of CPAP.
METHODS
A systematic review of electronic databases (Medline, Embase, and Cinahl) was performed using the medical subject heading terms, "CPAP" or "continuous positive airway pressure" and "animals" and "newborn." Abstracts were screened for inclusion using predetermined eligibility criteria.
RESULTS
In total, 235 abstracts were identified and screened for inclusion. Of these, 21 papers were included. Large (N = 18) and small (N = 3) animal models investigated the effects of CPAP. Pulmonary outcomes included gas exchange, lung structure and function, surfactant metabolism, lung inflammation and injury, and the effect of intrapulmonary therapy. Compared to mechanical ventilation, CPAP improves lung function, evokes less lung injury, and does not disrupt alveolar development. Surfactant administration combined with CPAP further improves respiratory outcomes. Of concern are findings that CPAP may increase airway reactivity.
DISCUSSION/CONCLUSION
CPAP offers numerous advantages over mechanical ventilation for the immature lung. The combination of CPAP and exogenous surfactant administration offers further pulmonary benefit.
Topics: Animals; Animals, Newborn; Continuous Positive Airway Pressure; Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 33091899
DOI: 10.1159/000511086 -
The Cochrane Database of Systematic... Oct 2020Respiratory distress, particularly respiratory distress syndrome (RDS), is the single most important cause of morbidity and mortality in preterm infants. In infants with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory distress, particularly respiratory distress syndrome (RDS), is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant has been the usual treatment, but it is invasive, potentially resulting in airway and lung injury. Continuous positive airway pressure (CPAP) has been used for the prevention and treatment of respiratory distress, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae.
OBJECTIVES
To determine the effect of continuous distending pressure in the form of CPAP on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.
SEARCH METHODS
We used the standard strategy of Cochrane Neonatal to search CENTRAL (2020, Issue 6); Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
All randomised or quasi-randomised trials of preterm infants with respiratory distress were eligible. Interventions were CPAP by mask, nasal prong, nasopharyngeal tube or endotracheal tube, compared with spontaneous breathing with supplemental oxygen as necessary.
DATA COLLECTION AND ANALYSIS
We used standard methods of Cochrane and its Neonatal Review Group, including independent assessment of risk of bias and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence. Subgroup analyses were planned on the basis of birth weight (greater than or less than 1000 g or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), timing of application (early versus late in the course of respiratory distress), pressure applied (high versus low) and trial setting (tertiary compared with non-tertiary hospitals; high income compared with low income) MAIN RESULTS: We included five studies involving 322 infants; two studies used face mask CPAP, two studies used nasal CPAP and one study used endotracheal CPAP and continuing negative pressure for a small number of less ill babies. For this update, we included one new trial. CPAP was associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.64, 95% confidence interval (CI) 0.50 to 0.82; typical risk difference (RD) -0.19, 95% CI -0.28 to -0.09; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 4 to 11; I = 50%; 5 studies, 322 infants; very low-certainty evidence), lower use of ventilatory assistance (typical RR 0.72, 95% CI 0.54 to 0.96; typical RD -0.13, 95% CI -0.25 to -0.02; NNTB 8, 95% CI 4 to 50; I = 55%; very low-certainty evidence) and lower overall mortality (typical RR 0.53, 95% CI 0.34 to 0.83; typical RD -0.11, 95% CI -0.18 to -0.04; NNTB 9, 95% CI 2 to 13; I = 0%; 5 studies, 322 infants; moderate-certainty evidence). CPAP was associated with increased risk of pneumothorax (typical RR 2.48, 95% CI 1.16 to 5.30; typical RD 0.09, 95% CI 0.02 to 0.16; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 7 to 50; I = 0%; 4 studies, 274 infants; low-certainty evidence). There was no evidence of a difference in bronchopulmonary dysplasia, defined as oxygen dependency at 28 days (RR 1.04, 95% CI 0.35 to 3.13; I = 0%; 2 studies, 209 infants; very low-certainty evidence). The trials did not report use of surfactant, intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis and neurodevelopment outcomes in childhood.
AUTHORS' CONCLUSIONS
In preterm infants with respiratory distress, the application of CPAP is associated with reduced respiratory failure, use of mechanical ventilation and mortality and an increased rate of pneumothorax compared to spontaneous breathing with supplemental oxygen as necessary. Three out of five of these trials were conducted in the 1970s. Therefore, the applicability of these results to current practice is unclear. Further studies in resource-poor settings should be considered and research to determine the most appropriate pressure level needs to be considered.
Topics: Bronchopulmonary Dysplasia; Continuous Positive Airway Pressure; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Outcome Assessment, Health Care; Pneumothorax; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Selection Bias; Treatment Failure
PubMed: 33058208
DOI: 10.1002/14651858.CD002271.pub3 -
Journal of Extracellular Vesicles Aug 2020Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors.... (Review)
Review
Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors. Most patients with severe COVID-19 infections who died had developed ARDS. Currently, ARDS is treated with supportive measures, but regenerative medicine approaches including extracellular vesicle (EV)-based therapies have shown promise. Herein, we aimed to analyse whether EV-based therapies could be effective in treating severe pulmonary conditions that affect COVID-19 patients and to understand their relevance for an eventual therapeutic application to human patients. Using a defined search strategy, we conducted a systematic review of the literature and found 39 articles (2014-2020) that reported effects of EVs, mainly derived from stem cells, in lung injury models (one large animal study, none in human). EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production). These effects were mediated by the release of EV cargo and identified factors including miRs-126, -30b-3p, -145, -27a-3p, syndecan-1, hepatocyte growth factor and angiopoietin-1. This review indicates that EV-based therapies hold great potential for COVID-19 related lung injuries as they target multiple pathways and enhance tissue regeneration. However, before translating EV therapies into human clinical trials, efforts should be directed at developing good manufacturing practice solutions for EVs and testing optimal dosage and administration route in large animal models.
PubMed: 32944185
DOI: 10.1080/20013078.2020.1795365 -
Pediatric Pulmonology Sep 2020To investigate the effect of nasal continuous positive airway pressure (NCPAP) given with nasal masks (NM) compared with binasal prongs (BNP) on the incidence of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the effect of nasal continuous positive airway pressure (NCPAP) given with nasal masks (NM) compared with binasal prongs (BNP) on the incidence of intubation within 72 hours in preterm infants (primary outcome) via meta-analysis of clinical studies.
DATA SOURCES
We searched for randomized clinical trials (RCTs) or quasi-RCTs in Medline, PubMed, and Web of Science from inception through 4 December 2019.
DATA EXTRACTION/SYNTHESIS
Two independent co-authors extracting data performed the meta-analysis using a fixed-effect model to yield pooled relative risk (RR) and its 95% confidence interval (CI) for each outcome. We used Cochrane GRADE to evaluate the evidence quality.
RESULTS
Eleven RCTs met the inclusion criteria. The meta-analysis showed NCPAP provided via NM significantly reduced the rate of intubation within 72 hours (RR, 0.72; 95% CI, 0.58-0.90; nine studies; GRADE-moderate) and nasal trauma (RR, 0.64; 95% CI, 0.55-0.74; GRADE-low) compared with NCPAP provided via BNP. Also, NCPAP via NM significantly reduced surfactant treatment (RR, 0.85; 95% CI, 0.74-0.97; GRADE-very low) and bronchopulmonary dysplasia (RR, 0.47; 95% CI, 0.23-0.95; GRADE-low) compared with BNP in a setting where NCPAP was used as the primary support in respiratory distress syndrome. No statistically significant differences were noted between groups in secondary outcomes except increased NCPAP duration when NCPAP given with NM compared with BNP (mean difference [days], 1.78; 95% CI, 1.67-1.89; GRADE-low).
CONCLUSION
Among premature infants, NCPAP provided with NM is more effective in preventing intubation and mechanical ventilation within 72 hours of initiating the support compared with NCPAP provided with BNP.
Topics: Bronchopulmonary Dysplasia; Continuous Positive Airway Pressure; Humans; Infant, Newborn; Infant, Premature; Masks; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 32478923
DOI: 10.1002/ppul.24878 -
Acta Paediatrica (Oslo, Norway : 1992) Nov 2020Surfactant delivery is a cornerstone for managing respiratory distress in preterm neonates, but data on the best surfactant delivery methods have been conflicting. (Review)
Review
Systematic review found that using thin catheters to deliver surfactant to preterm neonates was associated with reduced bronchopulmonary dysplasia and mechanical ventilation.
AIM
Surfactant delivery is a cornerstone for managing respiratory distress in preterm neonates, but data on the best surfactant delivery methods have been conflicting.
METHODS
A systematic literature review using the PubMed, Embase, Cochrane Library and Web of Science databases identified papers published up to November 5, 2019. Additional studies were identified from trial registries, conference proceedings and the reference lists of the selected papers.
RESULTS
We identified 15 studies covering 4926 preterm infants. The randomised controlled trials (RCTs) and observational studies both showed significant reductions in early intubation rates with use of thin catheters. The relative risk (RR) was 0.63 and the 95% confidence interval (95% CI) was 0.55-0.72 (P < .01), with an odds ratio (OR) of 0.40 and 95% CI of 0.35-0.45 (P < .0001). The collective results from the RCTs revealed a significant decrease in bronchopulmonary dysplasia (BPD) rates in the thin catheter group (RR, 0.47; 95% CI 0.33-0.66; P < .01). These findings were consistent with the observational studies (OR 0.47; 95% CI 0.43-0.52; P < .01).
CONCLUSION
Using thin catheters to deliver surfactant in comparison with intubate-surfactant-extubate (INSURE) to newborn preterm infants with respiratory distress was associated with a reduced incidence of BPD and less need for mechanical ventilation.
Topics: Bronchopulmonary Dysplasia; Catheters; Humans; Infant; Infant, Newborn; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 32441829
DOI: 10.1111/apa.15374 -
Journal of Comparative Effectiveness... Jun 2020To conduct a systematic overview of systematic reviews (SRs) and randomized clinical trials (RCTs) on surfactant therapy in neonatal meconium aspiration syndrome. We...
To conduct a systematic overview of systematic reviews (SRs) and randomized clinical trials (RCTs) on surfactant therapy in neonatal meconium aspiration syndrome. We searched EMBASE, PROQUEST and PubMed to summarize the different effects of surfactant lung lavage and bolus surfactant therapies in neonates with meconium aspiration syndrome. With a total of 1377 patients, three SRs and two RCTs were included in analysis. Surfactant effectiveness was concluded by low-quality SRs, with high risk of bias, which was contradicted by high-quality SRs, with low risk of bias. In SRs, the surfactant lung lavage reduced mortality, need for extracorporeal membrane oxygenation and hospitalization, while the bolus surfactant did not. In recent high-quality RCTs, however, the two modalities did not significantly differ. The evidence on surfactant effectiveness and its method of administration is sparse and inconsistent.
Topics: Bronchoalveolar Lavage; Clinical Trials as Topic; Female; Humans; Infant, Newborn; Male; Meconium Aspiration Syndrome; Pulmonary Surfactants; Systematic Reviews as Topic; Treatment Outcome
PubMed: 32394731
DOI: 10.2217/cer-2020-0018 -
Medicine Apr 2020The aim of the study was to estimate and compare the diagnostic accuracy of serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) for identifying... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
The aim of the study was to estimate and compare the diagnostic accuracy of serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) for identifying interstitial lung disease (ILD) from non-ILD among connective tissue disease (CTD) patients.
MATERIALS AND METHODS
Original articles on the diagnostic accuracy of serum KL-6 and SP-D in differentiating CTD-ILD from CTD-nonILD were identified from three public databases. The overall quality of evidence and methodologic quality of each eligible study were assessed by the Grading of Recommendations, Assessment, Development and Evaluation approach and Quality Assessment of Diagnostic Accuracy Studies, respectively. We used the bivariate model to calculate random-effect sensitivity, specificity, likelihood ratios, and area under curve. Furthermore, trial sequential analysis (TSA) was used to determine whether sample sizes incorporated in the meta-analysis were powerful for evaluating the diagnostic utility. Bayesian network analysis was performed to compare the diagnostic accuracy of 2 serum biomarkers in differentiating ILD among CTD patients and various subgroups.
RESULTS
Twenty-nine studies were included in the quantitative synthesis. No threshold effects were observed (all P values >.05). For diagnosis of ILD among CTD patients, overall sensitivity and specificity of serum KL-6 were 0.76 (95% confidence interval [CI]: 0.68-0.82) and 0.89 (95% CI: 0.83-0.93), whereas those for serum SP-D were 0.65 (95% CI: 0.45-0.80) and 0.88 (95% CI: 0.80-0.93). Comprehensive comparison of 2 circulating biomarkers using back-calculated likelihood ratio (LR) demonstrated that serum KL-6 corresponded to a higher LR+ and a lower LR- in comparison to serum SP-D, as well as in SSc-ILD. TSA indicated that evidence for serum KL-6 and SP-D in identifying CTD-ILD is powerful; nonetheless, more trials were needed for validation of serum KL-6 and SP-D in differentiating CTD-ILD subtypes, including different CTD and ethnicities.
CONCLUSIONS
This meta-analysis suggested that serum KL-6 had superior diagnostic accuracy to SP-D for differentiating ILD from non-ILD among CTD patients, providing a convenient and non-invasive approach for screening and management of ILD among CTD patients.
Topics: Biomarkers; Connective Tissue Diseases; Diagnosis, Differential; Humans; Lung Diseases, Interstitial; Mucin-1; Pulmonary Surfactant-Associated Protein D
PubMed: 32311947
DOI: 10.1097/MD.0000000000019695