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Jornal de Pediatria 2024To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax,... (Meta-Analysis)
Meta-Analysis Review
Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses.
OBJECTIVES
To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality.
METHODS
A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics.
RESULTS
Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group.
CONCLUSION
This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Surface-Active Agents; Airway Extubation; Pneumothorax; Pulmonary Surfactants; Intubation; Respiratory Distress Syndrome, Newborn; Cerebral Hemorrhage
PubMed: 37353207
DOI: 10.1016/j.jped.2023.05.008 -
The Clinical Respiratory Journal May 2024This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment... (Review)
Review
This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.
Topics: Humans; Pulmonary Surfactants; Contusions; Lung Injury; Respiratory Distress Syndrome; Animals; Respiration, Artificial; Treatment Outcome; Bronchoscopy
PubMed: 38778673
DOI: 10.1111/crj.13776 -
European Respiratory Review : An... Dec 2023Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP.
METHODS
We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946-1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM-CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide ( ) % predicted) and arterial-alveolar oxygen gradient.
RESULTS
Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference -8.09, 95% CI -11.88- -4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI -2.76-46.19 m, p=0.08), gas diffusion ( % predicted) (mean difference 5.09%, 95% CI 2.05-8.13%, p=0.001) and arterial-alveolar oxygen gradient (mean difference -4.36 mmHg, 95% CI -7.19- -1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I=0%). No serious trial-related adverse events were reported.
CONCLUSIONS
Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.
Topics: Humans; Pulmonary Alveolar Proteinosis; Granulocyte-Macrophage Colony-Stimulating Factor; Administration, Inhalation; Oxygen
PubMed: 37993127
DOI: 10.1183/16000617.0080-2023 -
PloS One 2023Timely application of surfactant replacement therapy is critical for neonates with respiratory distress syndrome (RDS). Presently, early clinical decision on surfactant... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Timely application of surfactant replacement therapy is critical for neonates with respiratory distress syndrome (RDS). Presently, early clinical decision on surfactant use relies solely on ventilator parameters. However, ventilator parameters are unable to truly recapitulate the extent of surfactant deficiency. Lung ultrasound has been increasingly used in the early prediction of surfactant use in recent years, but its predictive value remains unclear. Therefore, we conducted this study to examine its predictive value in surfactant use and determine the optimal timing and cutoff value.
METHODS
Studies on neonates with respiratory distress or diagnosed with RDS were collected from PubMed, Embase, Cochrane Library, and Web of Science. Primary outcomes included sensitivity, specificity, and positive and negative predictive values of lung ultrasound.
RESULTS
Ten eligible studies with 1162 participants were included. The sensitivity and specificity of lung ultrasound in predicting surfactant use were 0.86 (95% CI: 0.81-0.90) and 0.82 (95% CI: 0.71-0.90), respectively. Lung ultrasound performed within 1-3 h after birth had a sensitivity of 0.89 (95% CI: 0.79-0.95) and a Youden's index of 0.67. Compared with a lung ultrasound score (LUS) cutoff of ≤6/7, ≤8, >5, >6/7, and >8, a LUS cutoff of ≤5 had higher Youden's index (0.73) and sensitivity (0.94, 95% CI: 0.85-0.97) in predicting surfactant use.
CONCLUSIONS
Lung ultrasound is effective for predicting surfactant use in neonates. Lung ultrasound within 1-3 h after birth and a LUS cutoff of 5 are recommended. However, the symptoms and oxygenation of the neonatal patients must also be considered.
Topics: Infant, Newborn; Humans; Surface-Active Agents; Lung; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Ultrasonography; Lipoproteins
PubMed: 37498845
DOI: 10.1371/journal.pone.0287758 -
American Journal of Perinatology May 2024This study aimed to compare the safety and efficacy of intratracheal administration of budesonide and surfactant with surfactant alone for bronchopulmonary dysplasia... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to compare the safety and efficacy of intratracheal administration of budesonide and surfactant with surfactant alone for bronchopulmonary dysplasia (BPD) prevention in premature infants with respiratory distress syndrome.
STUDY DESIGN
A literature search was performed in MEDLINE, Embase, Cochrane, ClinicalTrials.gov, and gray literature. Assessment of quality was conducted using CASP tool, ROBIS tool, and GRADE framework.
RESULTS
A systematic review and meta-analysis and three observational studies were identified. Budesonide was associated with reduced incidence and severity of BPD, reduced mortality, patent ductus arteriosus, need for additional surfactant doses, hypotension, duration of invasive ventilation, hospital stays, salbutamol prescriptions, and hospitalizations in the first 2 years of life. The safety of budesonide on neurodevelopmental outcomes at 2 to 3 years of corrected age was reported.
CONCLUSION
Budesonide might be associated with a reduction in BPD incidence and severity, without evidence of impaired neurodevelopment at 2 to 3 years of age. According to the GRADE framework, the level of evidence is low due to significant heterogeneity of studies and other bias.
KEY POINTS
· BPD prevention is urgently needed.. · Intratracheal budesonide and surfactant for neonatal RDS could reduce BPD.. · The grade of evidence for this intervention is low due to study heterogeneity and other bias..
Topics: Humans; Budesonide; Bronchopulmonary Dysplasia; Pulmonary Surfactants; Infant, Newborn; Infant, Premature; Respiratory Distress Syndrome, Newborn; Glucocorticoids
PubMed: 37279790
DOI: 10.1055/s-0043-1769795 -
Archives of Disease in Childhood. Fetal... Jul 2023To perform a network meta-analysis of randomised controlled trials of different surfactant treatment strategies for respiratory distress syndrome (RDS) to assess if a... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To perform a network meta-analysis of randomised controlled trials of different surfactant treatment strategies for respiratory distress syndrome (RDS) to assess if a certain fraction of inspired oxygen (FiO) is optimal for selective surfactant therapy.
DESIGN
Systematic review and network meta-analysis using Bayesian analysis of randomised trials of prophylactic versus selective surfactant for RDS.
SETTING
Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Science Citation Index Expanded.
PATIENTS
Randomised trials including infants under 32 weeks of gestational age.
INTERVENTIONS
Intratracheal surfactant, irrespective of type or dose.
MAIN OUTCOME MEASURES
Our primary outcome was neonatal mortality, compared between groups treated with selective surfactant therapy at different thresholds of FiO. Secondary outcomes included respiratory morbidity and major complications of prematurity.
RESULTS
Of 4643 identified references, 14 studies involving 5298 participants were included. We found no statistically significant differences between 30%, 40% and 50% FiO thresholds. A sensitivity analysis of infants treated in the era of high antenatal steroid use and nasal continuous positive airway pressure as initial mode of respiratory support showed no difference in mortality, RDS or intraventricular haemorrhage alone but suggested an increase in the combined outcome of major morbidities in the 60% threshold.
CONCLUSION
Our results do not show a clear benefit of surfactant treatment at any threshold of FiO. The 60% threshold was suggestive of increased morbidity. There was no advantage seen with prophylactic treatment. Randomised trials of different thresholds for surfactant delivery are urgently needed to guide clinicians and provide robust evidence.
PROSPERO REGISTRATION NUMBER
CRD42020166620.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Surface-Active Agents; Network Meta-Analysis; Bayes Theorem; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 36600484
DOI: 10.1136/archdischild-2022-324184 -
Respiratory Medicine Dec 2023Acute endurance exercise may induce airway epithelium injury. However, the response of epithelial integrity markers of the airways including club cell secretory protein... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acute endurance exercise may induce airway epithelium injury. However, the response of epithelial integrity markers of the airways including club cell secretory protein (CC16) and surfactant protein D (SP-D) to endurance exercise have not been systematically reviewed. Therefore, the aim of this systematic review and meta-analysis was to assess the acute effects of endurance exercise on markers of epithelial integrity of the airways (CC16, SP-D and the CC16/SP-D ratio) in athletes and non-athletes.
METHODS
A systematic search was performed utilizing PubMed/Medline, EMBASE, Web of Science, and hand searching bibliographies of retrieved articles through to September 2022. Based on the inclusion criteria, articles with available data about the acute effects of endurance exercise on serum or plasma concentrations of CC16, SP-D and CC16/SP-D ratio in athletes and non-athletes were included. Quality assessment of studies and statistical analysis were conducted via Review Manager 5.4 software.
RESULTS
The search resulted in 908 publications. Finally, thirteen articles were included in the review. Acute endurance exercise resulted in an increase in CC16 (P = 0.0006, n = 13) and CC16/SP-D ratio (P = 0.005, n = 2) whereas SP-D (P = 0.47, n = 3) did not change significantly. Subgroup analysis revealed that the type (P = 0.003), but not the duration of exercise (P = 0.77) or the environmental temperature (P = 0.06) affected the CC16 response to endurance exercise.
CONCLUSIONS
Acute endurance exercise increases CC16 and the CC16/SP-D ratio, as markers of epithelial integrity, but not SP-D in athletes and non-athletes.
Topics: Humans; Athletes; Exercise; Exercise Test; Exercise Therapy; Pulmonary Surfactant-Associated Protein D
PubMed: 37951313
DOI: 10.1016/j.rmed.2023.107457 -
Cureus Dec 2023Preterm birth causes constant challenges, with bronchopulmonary dysplasia (BPD) being a major concern. Immediately after birth, it takes time to establish feeding... (Review)
Review
Preterm birth causes constant challenges, with bronchopulmonary dysplasia (BPD) being a major concern. Immediately after birth, it takes time to establish feeding between the mother and the premature baby. During this time, the telological shifting of fluid from extracellular space to intracellular space will help the baby; this transition should be smooth. Both normal physiologic changes and pathophysiologic events are capable of disrupting this delicate fluid shifting that occurs in very low-birth-weight infants during the first week of life. The immaturity of the renal system and evaporative losses complicate this process. This lack of fluid displacement can be associated with an increased amount of water in the lungs and reduced lung compliance. This can lead to the need for more ventilatory support and a higher oxygen requirement, which, in turn, leads to lung damage. The fluid restriction is also associated with complications such as severe dehydration, intracranial hemorrhage, and bilirubin toxicity. However, the administration of large amounts of fluid and salt is associated with an increased incidence of patent ductus arteriosus, BPD, necrotizing enterocolitis, and intraventricular hemorrhage. There were studies conducted in both the pre-surfactant and surfactant eras that were inconclusive regarding fluid restriction in BPD. We only included very recent studies. This systematic review attempts to summarize the current evidence, focusing on the efficacy and safety of early fluid management in preterm infants. This reduces the risk of BPD and improves outcomes for premature infants. As we know, intact survival is very important. Our review supported the early fluid restriction.
PubMed: 38249238
DOI: 10.7759/cureus.50805 -
The Cochrane Database of Systematic... Oct 2023Administration of various exogenous surfactant preparations has been shown to decrease lung injury and pneumothorax and improve survival in very preterm infants with... (Review)
Review
BACKGROUND
Administration of various exogenous surfactant preparations has been shown to decrease lung injury and pneumothorax and improve survival in very preterm infants with respiratory distress syndrome (RDS). There is no consensus on the threshold for surfactant administration, to allow timely intervention and avoid over-treatment, also considering the invasiveness of the procedure and its cost. Rapid tests for lung maturity, which include the click test, lamellar body counts and stable microbubble test, might guide the identification of those infants needing surfactant administration.
OBJECTIVES
To assess the effects of surfactant treatment guided by rapid tests for surfactant deficiency in preterm infants at risk for or having RDS. Comparison 1: In preterm infants at risk for RDS, does surfactant treatment guided by rapid tests for surfactant deficiency compared to prophylactic surfactant administration to all high-risk infants minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality? Comparison 2: In preterm infants who require early respiratory support, does surfactant treatment guided by rapid tests for surfactant deficiency compared to surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality?
SEARCH METHODS
We searched in October 2022 CENTRAL, PubMed, Embase and three additional trial registries. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs evaluating rapid tests after birth for surfactant deficiency in infants at high risk of RDS or requiring respiratory support. We specified two comparisons: 1)surfactant treatment guided by rapid tests for surfactant deficiency versus prophylactic surfactant administration to all high-risk infants in extremely preterm (less than 28 weeks' gestation) and very preterm (28 to 32 weeks' gestation); 2)surfactant treatment guided by rapid tests for surfactant deficiency versus surfactant therapy provided to preterm infants (less than 37 weeks' gestation) with RDS diagnosed on clinical and radiologic criteria.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) and risk difference (RD), with their 95% confidence intervals (CIs) for dichotomous data. Our primary outcomes were: neonatal mortality, mortality prior to hospital discharge, bronchopulmonary dysplasia and the composite outcome bronchopulmonary dysplasia or mortality. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included three RCTs enrolling 562 newborn infants in this review. No studies compared surfactant treatment guided by rapid tests for surfactant deficiency versus prophylactic surfactant administration to all high-risk infants. Comparing surfactant therapy guided by rapid tests for surfactant deficiency versus surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria. No studies reported neonatal mortality. Compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria, the evidence is very uncertain about the effect of surfactant treatment guided by rapid tests for surfactant deficiency on mortality prior to hospital discharge: RR 1.25, 95% CI 0.65 to 2.41, RD 0.01, 95% CI -0.03 to 0.05, 562 participants, 3 studies; I² for RR and RD = 75% and 43%, respectively; very low-certainty evidence. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in bronchopulmonary dysplasia: RR 0.90, 95% CI 0.61 to 1.32, RD -0.02, 95% CI -0.08 to 0.04, 562 participants, 3 studies; I² for RR and RD = 0%; low-certainty evidence. No studies reported the composite outcome bronchopulmonary dysplasia or mortality. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in surfactant utilization (RR 0.97, 95% CI 0.85 to 1.11, RD -0.02, 95% CI -0.10 to 0.06, 562 participants, 3 studies, I² for RR and RD = 63% and 65%, respectively, low-certainty evidence), and any pneumothorax (RR 0.53, 95% CI 0.15 to 1.92, RD -0.01, 95% CI -0.04 to 0.01, 506 participants, 2 studies, I² for RR and RD = 0%, low-certainty evidence) compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria. No studies reported moderate to severe neurodevelopmental impairment. We identified two large ongoing RCTs.
AUTHORS' CONCLUSIONS
No studies compared surfactant treatment guided by rapid tests for surfactant deficiency to prophylactic surfactant administration to all high-risk infants. Low to very low-certainty evidence from three studies is available on surfactant therapy guided by rapid tests for surfactant deficiency versus surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria. No studies reported neonatal mortality, the composite outcome 'bronchopulmonary dysplasia or mortality', or neurodevelopmental outcomes. Compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria, the evidence is very uncertain about the effect of surfactant treatment guided by rapid tests for surfactant deficiency on mortality prior to hospital discharge. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in bronchopulmonary dysplasia, surfactant utilization and any pneumothorax. The findings of the two large ongoing trials identified in this review are likely to have an important impact on establishing the effects of surfactant treatment guided by rapid tests for surfactant deficiency in preterm infants.
Topics: Infant, Newborn; Infant; Humans; Surface-Active Agents; Bronchopulmonary Dysplasia; Pneumothorax; Infant, Premature; Respiratory Distress Syndrome, Newborn; Pulmonary Surfactants; Lung
PubMed: 37882216
DOI: 10.1002/14651858.CD013158.pub2 -
Thorax Aug 2023Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We aimed to systematically review evidence of soluble markers in peripheral blood or bronchoalveolar lavage fluid (BALF) as biomarkers in SSc-ILD.
METHOD
Five databases were screened for observational or interventional, peer-reviewed studies in adults published between January 2000 and September 2021 that assessed levels of biomarkers in peripheral blood or BALF of SSc-ILD patients compared with healthy controls. Qualitative assessment was performed using Critical Appraisal Skills Programme (CASP) checklists. Standardised mean difference (SMD) in biomarkers were combined in random-effects meta-analyses where multiple independent studies reported quantitative data.
RESULTS
768 published studies were identified; 38 articles were included in the qualitative synthesis. Thirteen studies were included in the meta-analyses representing three biomarkers: KL6, SP-D and IL-8. Greater IL-8 levels were associated with SSc-ILD in both peripheral blood and BALF, overall SMD 0.88 (95% CI 0.61 to 1.15; I=1%). Greater levels of SP-D and KL-6 were both estimated in SSc-ILD peripheral blood compared with healthy controls, at an SMD of 1.78 (95% CI 1.50 to 2.17; I=8%) and 1.66 (95% CI 1.17 to 2.14; I=76%), respectively.
CONCLUSION
We provide robust evidence that KL-6, SP-D and IL-8 have the potential to serve as reliable biomarkers in blood/BALF for supporting the diagnosis of SSc-ILD. However, while several other biomarkers have been proposed, the evidence of their independent value in diagnosis and prognosis is currently lacking and needs further investigation.
PROSPERO REGISTRATION NUMBER
CRD42021282452.
Topics: Adult; Humans; Lung Diseases, Interstitial; Interleukin-8; Pulmonary Surfactant-Associated Protein D; Scleroderma, Systemic; Biomarkers; Lung
PubMed: 36261273
DOI: 10.1136/thorax-2022-219226