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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 -
The Journal of Maternal-fetal &... Dec 2023Surfactant protein SP-B, an important protein in pulmonary surfactant, is required for the stabilization of surfactant films in the lung and maintenance of postnatal... (Meta-Analysis)
Meta-Analysis
Surfactant protein SP-B, an important protein in pulmonary surfactant, is required for the stabilization of surfactant films in the lung and maintenance of postnatal lung function. Although the association between SP-B polymorphisms and the risk of neonatal respiratory distress syndrome (RDS) has been evaluated, the results have been inconsistent. We investigated the association between SP-B polymorphisms and the risk of neonatal RDS. Relevant studies were systematically searched in PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) electronic databases until June 2022. Data were collected independently by two reviewers and converted to odds ratios (ORs) with 95% confidence intervals (CIs). Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias assessment were performed using Stata 12.1 software and Review Manager 5.3. Fourteen studies were included. C1580T polymorphism was significantly associated with neonatal RDS in five genetic models (T vs. C: OR = 0.70, 95% CI 0.57-0.86, I = 78%; TT vs. CC: OR = 0.63, 95% CI 0.53-0.86, I = 39%; CT vs. CC: OR = 0.65, 95% CI 0.50-0.84, I = 54%; TT + CT vs. CC: OR = 0.62, 95% CI 0.49-0.78, I = 59%; TT vs. CC + CT: OR = 0.78, 95% CI 0.67-0.91, I = 43%). The CT and TT genotypes may decrease the risk of RDS in neonates. Subgroup analyses revealed that the association of C1580T polymorphism with neonatal RDS was stable, independent of preterm birth and Hardy-Weinberg equilibrium. In addition, the Han Chinese were more likely to be affected by C1580T polymorphisms than Caucasians and Finnish. Our findings suggest that C1580T polymorphism may be a protective factor against neonatal RDS.
Topics: Female; Humans; Infant, Newborn; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Premature Birth; Respiratory Distress Syndrome, Newborn; Pulmonary Surfactants
PubMed: 37527966
DOI: 10.1080/14767058.2023.2240469 -
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 -
Journal of Medical Toxicology :... Jul 2021Vitamin E acetate (VEA) has come under significant scrutiny due to its association with E-cigarette or vaping product use-associated lung injury (EVALI). Various...
BACKGROUND
Vitamin E acetate (VEA) has come under significant scrutiny due to its association with E-cigarette or vaping product use-associated lung injury (EVALI). Various theoretical mechanisms have been proposed for toxicity, including tocopherol (vitamin E)-mediated surfactant damage, recruitment of inflammation, and pyrolysis of acetate to the pulmonary irritant ketene.
OBJECTIVE
Characterize studies in mammals evaluating inhaled VEA, vitamin E analogues, or pyrolyzed acetate that describe subsequent effects on the lung.
ELIGIBILITY
Research in all languages from time of inception to October 1, 2020, regarding mammals (human or animal) exposed to inhaled vitamin E analogues, or any compound containing acetate administered via inhalation after pyrolysis, and subsequent description of pulmonary effect.
SOURCES OF EVIDENCE
Ovid MEDLINE, Scopus, and Web of Science Core Collection.
RESULTS
In total, 786 unique articles were identified. After duplicate reviewer screening, 16 articles were eligible for inclusion. Tocopherol was evaluated in 68.8% (11/16) of the studies, VEA in 18.8% (3/16), and both VEA and tocopherol were evaluated in 12.5% (2/16). Of the five studies evaluating VEA, it was given by pyrolysis in 60.0% (3/5). No human studies were identified. All included trials were conducted on non-human mammals: 75.0% (12/16) rodent models and 25.0% (4/16) sheep models. Outcomes assessed were heterogeneous and included 57 unique outcomes.
CONCLUSIONS
Several questions still exist regarding the pulmonary toxicity of inhaled tocopherol and VEA. More studies are needed to determine whether tocopherol alone (i.e., without acetate) can cause pulmonary injury. Additionally, further studies of VEA should evaluate the impact that pyrolysis and co-administration with other compounds, such as tetrahydrocannabinol, have on the toxic potential of VEA.
Topics: Acetates; Adult; Aged; Aged, 80 and over; Animals; Electronic Nicotine Delivery Systems; Female; Humans; Inhalation Exposure; Lung Injury; Male; Middle Aged; Models, Animal; Vaping; Vitamin E
PubMed: 33528766
DOI: 10.1007/s13181-021-00823-w -
The Cochrane Database of Systematic... Jul 2019Acute respiratory distress syndrome (ARDS) is a life-threatening condition caused by direct or indirect injury to the lungs. Despite improvements in clinical management...
BACKGROUND
Acute respiratory distress syndrome (ARDS) is a life-threatening condition caused by direct or indirect injury to the lungs. Despite improvements in clinical management (for example, lung protection strategies), mortality in this patient group is at approximately 40%. This is an update of a previous version of this review, last published in 2004.
OBJECTIVES
To evaluate the effectiveness of pharmacological agents in adults with ARDS on mortality, mechanical ventilation, and fitness to return to work at 12 months.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and CINAHL on 10 December 2018. We searched clinical trials registers and grey literature, and handsearched reference lists of included studies and related reviews.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing pharmacological agents with control (placebo or standard therapy) to treat adults with established ARDS. We excluded trials of nitric oxide, inhaled prostacyclins, partial liquid ventilation, neuromuscular blocking agents, fluid and nutritional interventions and medical oxygen. We excluded studies published earlier than 2000, because of changes to lung protection strategies for people with ARDS since this date.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE.
MAIN RESULTS
We included 48 RCTs with 6299 participants who had ARDS; two included only participants with mild ARDS (also called acute lung injury). Most studies included causes of ARDS that were both direct and indirect injuries. We noted differences between studies, for example the time of administration or the size of dose, and because of unclear reporting we were uncertain whether all studies had used equivalent lung protection strategies.We included five types of agents as the primary comparisons in the review: corticosteroids, surfactants, N-acetylcysteine, statins, and beta-agonists. We included 15 additional agents (sivelestat, mesenchymal stem cells, ulinastatin, anisodimine, angiotensin-converting enzyme (ACE) inhibitor, recombinant human ACE2 (palifermin), AP301, granulocyte-macrophage colony stimulating factor (GM-CSF), levosimendan, prostacyclins, lisofylline, ketaconazole, nitroglycerins, L-2-oxothiazolidine-4-carboxylic acid (OTZ), and penehyclidine hydrochloride).We used GRADE to downgrade outcomes for imprecision (because of few studies and few participants), for study limitations (e.g. high risks of bias) and for inconsistency (e.g. differences between study data).Corticosteroids versus placebo or standard therapyCorticosteroids may reduce all-cause mortality within three months by 86 per 1000 patients (with as many as 161 fewer to 19 more deaths); however, the 95% confidence interval (CI) includes the possibility of both increased and reduced deaths (risk ratio (RR) 0.77, 95% CI 0.57 to 1.05; 6 studies, 574 participants; low-certainty evidence). Due to the very low-certainty evidence, we are uncertain whether corticosteroids make little or no difference to late all-cause mortality (later than three months) (RR 0.99, 95% CI 0.64 to 1.52; 1 study, 180 participants), or to the duration of mechanical ventilation (mean difference (MD) -4.30, 95% CI -9.72 to 1.12; 3 studies, 277 participants). We found that ventilator-free days up to day 28 (VFD) may be improved with corticosteroids (MD 4.09, 95% CI 1.74 to 6.44; 4 studies, 494 participants; low-certainty evidence). No studies reported adverse events leading to discontinuation of study medication, or fitness to return to work at 12 months (FTR).Surfactants versus placebo or standard therapyWe are uncertain whether surfactants make little or no difference to early mortality (RR 1.08, 95% CI 0.91 to 1.29; 9 studies, 1338 participants), or whether they reduce late all-cause mortality (RR 1.28, 95% CI 1.01 to 1.61; 1 study, 418 participants). Similarly, we are uncertain whether surfactants reduce the duration of mechanical ventilation (MD -2.50, 95% CI -4.95 to -0.05; 1 study, 16 participants), make little or no difference to VFD (MD -0.39, 95% CI -2.49 to 1.72; 2 studies, 344 participants), or to adverse events leading to discontinuation of study medication (RR 0.50, 95% CI 0.17 to 1.44; 2 studies, 88 participants). We are uncertain of these effects because we assessed them as very low-certainty. No studies reported FTR.N-aceytylcysteine versus placeboWe are uncertain whether N-acetylcysteine makes little or no difference to early mortality, because we assessed this as very low-certainty evidence (RR 0.64, 95% CI 0.32 to 1.30; 1 study, 36 participants). No studies reported late all-cause mortality, duration of mechanical ventilation, VFD, adverse events leading to study drug discontinuation, or FTR.Statins versus placeboStatins probably make little or no difference to early mortality (RR 0.99, 95% CI 0.78 to 1.26; 3 studies, 1344 participants; moderate-certainty evidence) or to VFD (MD 0.40, 95% CI -0.71 to 1.52; 3 studies, 1342 participants; moderate-certainty evidence). Statins may make little or no difference to duration of mechanical ventilation (MD 2.70, 95% CI -3.55 to 8.95; 1 study, 60 participants; low-certainty evidence). We could not include data for adverse events leading to study drug discontinuation in one study because it was unclearly reported. No studies reported late all-cause mortality or FTR.Beta-agonists versus placebo controlBeta-blockers probably slightly increase early mortality by 40 per 1000 patients (with as many as 119 more or 25 fewer deaths); however, the 95% CI includes the possibility of an increase as well as a reduction in mortality (RR 1.14, 95% CI 0.91 to 1.42; 3 studies, 646 participants; moderate-certainty evidence). Due to the very low-certainty evidence, we are uncertain whether beta-agonists increase VFD (MD -2.20, 95% CI -3.68 to -0.71; 3 studies, 646 participants), or make little or no difference to adverse events leading to study drug discontinuation (one study reported little or no difference between groups, and one study reported more events in the beta-agonist group). No studies reported late all-cause mortality, duration of mechanical ventilation, or FTR.
AUTHORS' CONCLUSIONS
We found insufficient evidence to determine with certainty whether corticosteroids, surfactants, N-acetylcysteine, statins, or beta-agonists were effective at reducing mortality in people with ARDS, or duration of mechanical ventilation, or increasing ventilator-free days. Three studies awaiting classification may alter the conclusions of this review. As the potential long-term consequences of ARDS are important to survivors, future research should incorporate a longer follow-up to measure the impacts on quality of life.
Topics: Adrenal Cortex Hormones; Adult; Humans; Neuromuscular Blocking Agents; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome
PubMed: 31334568
DOI: 10.1002/14651858.CD004477.pub3 -
Neonatology 2020The INtubation-SURfactant-Extubation (INSURE) procedure is a widely-used surfactant administration method to treat preterm infants with respiratory distress syndrome...
The INtubation-SURfactant-Extubation (INSURE) procedure is a widely-used surfactant administration method to treat preterm infants with respiratory distress syndrome (RDS) but is not always successful. We conducted a systematic review to identify early predictive factors for failure of this procedure. A systematic literature search was performed until July 2018 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Original studies comparing INSURE success with INSURE failure in preterm infants with RDS were included. A predefined data extraction form was used to retrieve data from articles, and methodological quality was assessed using the SIGN checklists. Fifteen studies out of 690 identified records met inclusion criteria. Methodological quality varied, only 8 studies performed multivariate analysis. We identified 20 different risk factors in total. Evidence for birth weight (BW) as a predictor for INSURE failure was inconsistent, but there was a significant association between decreasing gestational age (GA) and failure risk. RDS severity was assessed in multiple ways, using arterial blood gas values, imaging, and scoring systems. In conclusion, extremely low BW, low GA, and severe RDS appear to be risk factors for INSURE failure. However, evidence is inconsistent due to important methodological heterogeneity. Therefore, clinical applicability of these results is limited and implies the need for future large cohort studies on this subject.
Topics: Combined Modality Therapy; Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome, Newborn
PubMed: 31437836
DOI: 10.1159/000501654 -
The Cochrane Database of Systematic... Mar 2020At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs.
OBJECTIVES
To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth.
DATA COLLECTION AND ANALYSIS
We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review: mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40 (I² not applicable); typical RD 0.00, 95% CI -0.02 to 0.02; I² = 0%; 5 studies, 479 participants); and mortality during hospitalisation (typical RR 1.09, 95% CI 0.83 to 1.43; I² = 42%; typical RD 0.01, 95% CI -0.02 to 0.04; I² = 24%; 9 studies, 1458 participants). The quality of the evidence was low for death in the delivery room because of limitations in study design and imprecision of estimates (only one death was recorded across studies). For death before discharge the quality was moderate: with longer follow-up there were more deaths (n = 143) but limitations in study design remained. Among secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; I² = 95%; 5 studies, 524 participants; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study at high risk of bias: when this study was removed from the analysis, the size of the effect was reduced (MD -1.71 days, 95% CI -3.04 to -0.39; I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. risk of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.91, 95% CI 0.79 to 1.04; I² = 65%; 5 studies, 811 participants); risk of surfactant administration during hospital admission (typical RR 0.99, 95% CI 0.91 to 1.08; I² = 0%; 9 studies, 1458 participants); risk of chronic lung disease (typical RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants); pneumothorax (typical RR 0.89, 95% CI 0.57 to 1.40; I² = 34%; 8 studies, 1377 infants); or risk of patent ductus arteriosus requiring pharmacological treatment (typical RR 0.99, 95% CI 0.87 to 1.12; I² = 48%; 7 studies, 1127 infants). The quality of evidence for these secondary outcomes was moderate (limitations in study design ‒ GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates ‒ GRADE). We could not perform any meta-analysis in the comparison of the use of initial sustained inflation versus standard inflations in newborns receiving resuscitation with chest compressions because we identified only one trial for inclusion (a pilot study of nine preterm infants).
AUTHORS' CONCLUSIONS
Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review.
Topics: Cerebral Intraventricular Hemorrhage; Ductus Arteriosus, Patent; Heart Massage; Hospital Mortality; Humans; Infant, Newborn; Intubation, Intratracheal; Lung Diseases; Pneumothorax; Positive-Pressure Respiration; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Resuscitation; Time Factors
PubMed: 32187656
DOI: 10.1002/14651858.CD004953.pub4