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Early Human Development May 2023There is lack of evidence synthesis on the global consequences of bronchopulmonary dysplasia (BPD) in adolescence. (Review)
Review
BACKGROUND
There is lack of evidence synthesis on the global consequences of bronchopulmonary dysplasia (BPD) in adolescence.
AIM
Assess the impact of bronchopulmonary dysplasia on respiratory and non-respiratory outcomes in adolescents.
METHODS
A systematic review of studies assessing the outcomes of adolescents aged 10 to 19 years-old with BPD was conducted. We independently screened studies published until 6th March 2023 in PubMed® and Scopus® databases. Data on methodologic design, sample descriptive and findings were extracted from each study. Risk of bias was assessed using quality assessment tools.
RESULTS
Thirty-one studies were included. Adolescents with a history of BPD present with more respiratory symptoms (wheezing, respiratory exacerbations, need for respiratory medication) and twenty-five studies showed a reduction in pulmonary function, with varying impact according to BPD severity and no differences before and after the surfactant era. Spirometry evaluation throughout the years is not consensual, but methacholine and salbutamol response in BPD groups is increased compared to non-BPD groups. Markers of eosinophilic airway inflammation are not increased as in asthma patients. Exercise potential is identical, but data regarding physical capacity and activity are inconsistent. More frequent radiologic abnormalities translate into higher high-resolution computed tomography scores, with linear (72.2 %) and triangular subpleural opacities (58.3 %) as the most common findings. There is a higher risk for special needs in education, but quality of life seems to be equal to non-BPD adolescents.
CONCLUSIONS
BPD negatively impacts both pulmonary and non-pulmonary outcomes in adolescents.
Topics: Infant, Newborn; Humans; Adolescent; Child; Young Adult; Adult; Bronchopulmonary Dysplasia; Quality of Life; Lung; Asthma; Spirometry
PubMed: 36965348
DOI: 10.1016/j.earlhumdev.2023.105756 -
PloS One 2023Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants <29 weeks' gestation and the neurodevelopmental outcomes remain unclear. Thus, our objective was to systematically review and meta-analyze the efficacy and safety of STC compared to intubation for surfactant or nasal continuous positive airway pressure (nCPAP) in preterm infants with RDS.
METHODS
Medical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants < 29 weeks' gestation. The Cochrane risk of bias (ROB) tool was used and certainty of evidence (CoE) was rated according to GRADE.
RESULTS
Twenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants < 29 weeks' gestation, STC significantly reduced the risk of BPD compared to controls (6 RCTs, N = 980; RR 0.63; 95% CI 0.47 to 0.85; NNTB = 8; CoE: moderate).
CONCLUSIONS
Compared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation.
Topics: Infant, Newborn; Humans; Surface-Active Agents; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Continuous Positive Airway Pressure; Bronchopulmonary Dysplasia; Lipoproteins
PubMed: 37099568
DOI: 10.1371/journal.pone.0284792 -
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 -
The Cochrane Database of Systematic... Aug 2015A wide variety of surfactant preparations have been developed and tested including synthetic surfactants and surfactants derived from animal sources. Although clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A wide variety of surfactant preparations have been developed and tested including synthetic surfactants and surfactants derived from animal sources. Although clinical trials have demonstrated that both synthetic surfactant and animal derived surfactant preparations are effective, comparison in animal models has suggested that there may be greater efficacy of animal derived surfactant products, perhaps due to the protein content of animal derived surfactant.
OBJECTIVES
To compare the effect of animal derived surfactant to protein free synthetic surfactant preparations in preterm infants at risk for or having respiratory distress syndrome (RDS).
SEARCH METHODS
Searches were updated of the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014), PubMed, CINAHL and EMBASE (1975 through November 2014). All languages were included.
SELECTION CRITERIA
Randomized controlled trials comparing administration of protein free synthetic surfactants to administration of animal derived surfactant extracts in preterm infants at risk for or having respiratory distress syndrome were considered for this review.
DATA COLLECTION AND ANALYSIS
Data collection and analysis were conducted according to the standards of the Cochrane Neonatal Review Group.
MAIN RESULTS
Fifteen trials met the inclusion criteria. The meta-analysis showed that the use of animal derived surfactant rather than protein free synthetic surfactant resulted in a significant reduction in the risk of pneumothorax [typical relative risk (RR) 0.65, 95% CI 0.55 to 0.77; typical risk difference (RD) -0.04, 95% CI -0.06 to -0.02; number needed to treat to benefit (NNTB) 25; 11 studies, 5356 infants] and a marginal reduction in the risk of mortality (typical RR 0.89, 95% CI 0.79 to 0.99; typical RD -0.02, 95% CI -0.04 to -0.00; NNTB 50; 13 studies, 5413 infants).Animal derived surfactant was associated with an increase in the risk of necrotizing enterocolitis [typical RR 1.38, 95% CI 1.08 to 1.76; typical RD 0.02, 95% CI 0.01 to 0.04; number needed to treat to harm (NNTH) 50; 8 studies, 3462 infants] and a marginal increase in the risk of any intraventricular hemorrhage (typical RR 1.07, 95% CI 0.99 to 1.15; typical RD 0.02, 95% CI 0.00 to 0.05; 10 studies, 5045 infants) but no increase in Grade 3 to 4 intraventricular hemorrhage (typical RR 1.08, 95% CI 0.91 to 1.27; typical RD 0.01, 95% CI -0.01 to 0.03; 9 studies, 4241 infants).The meta-analyses supported a marginal decrease in the risk of bronchopulmonary dysplasia or mortality associated with the use of animal derived surfactant preparations (typical RR 0.95, 95% CI 0.91 to 1.00; typical RD -0.03, 95% CI -0.06 to 0.00; 6 studies, 3811 infants). No other relevant differences in outcomes were noted.
AUTHORS' CONCLUSIONS
Both animal derived surfactant extracts and protein free synthetic surfactant extracts are effective in the treatment and prevention of respiratory distress syndrome. Comparative trials demonstrate greater early improvement in the requirement for ventilator support, fewer pneumothoraces, and fewer deaths associated with animal derived surfactant extract treatment. Animal derived surfactant may be associated with an increase in necrotizing enterocolitis and intraventricular hemorrhage, though the more serious hemorrhages (Grade 3 and 4) are not increased. Despite these concerns, animal derived surfactant extracts would seem to be the more desirable choice when compared to currently available protein free synthetic surfactants.
Topics: Animals; Cerebral Hemorrhage; Drug Combinations; Enterocolitis, Necrotizing; Fatty Alcohols; Humans; Infant, Newborn; Infant, Premature; Polyethylene Glycols; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 26301526
DOI: 10.1002/14651858.CD000144.pub3 -
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 -
European Respiratory Review : An... Sep 2018Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes,...
Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes, such as surfactant protein C (), surfactant protein A1 and A2 ( and ), ATP binding cassette A3 () and Hermansky-Pudlak syndrome (, and ), develop progressive pulmonary fibrosis, often culminating in fatal respiratory insufficiency. Although many mutations have been described, little is known about the optimal treatment strategy for fibrotic interstitial pneumonia patients with surfactant-processing mutations.We performed a systematic literature review of studies that described a drug effect in patients, cell or mouse models with a surfactant-processing mutation. In total, 73 articles were selected, consisting of 55 interstitial lung disease case reports/series, two clinical trials and 16 cell or mouse studies. Clinical effect parameters included lung function, radiological characteristics and clinical symptoms, while experimental outcome parameters included chemokine/cytokine expression, surfactant trafficking, necrosis and apoptosis. SP600125, a c-jun N-terminal kinase (JNK) inhibitor, hydroxychloroquine and 4-phenylbutyric acid were most frequently studied in disease models and lead to variable outcomes, suggesting that outcome is mutation dependent.This systematic review summarises effect parameters for future studies on surfactant-processing disorders in disease models and provides directions for future trials in affected patients.
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Idiopathic Interstitial Pneumonias; Lung; Mice; Mutation; Phenotype; Pulmonary Surfactant-Associated Proteins; Respiratory System Agents; Treatment Outcome
PubMed: 29997245
DOI: 10.1183/16000617.0135-2017 -
Experimental and Therapeutic Medicine Jan 2013Acute respiratory distress syndrome (ARDS) is often characterized by reduced lung compliance, which suggests dysfunction of the endogenous surfactant system. The...
Acute respiratory distress syndrome (ARDS) is often characterized by reduced lung compliance, which suggests dysfunction of the endogenous surfactant system. The effectiveness of exogenous surfactants as replacements for the endogenous system in the treatment of ARDS in adults was assessed. Randomized controlled trials from Medline (1950-2011), Embase (1989-2011), the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (1994-2011) were analyzed. Two reviewers identified trials for inclusion and the results of included trials were quantitatively pooled with a fixed-effects model. Seven trials (2,144 patients) with good methodological quality were included in the analysis. Pulmonary surfactant treatment was not associated with reduced mortality [relative risk (RR), 1.00; 95% confidence interval (CI) 0.89-1.12]. Subgroup analysis revealed no reduced mortality for various surfactant types. Heterogeneity was not significant in the primary outcome analysis (I(2)=0%). There was no evidence of publication bias. Oxygenation, ventilation-free days, duration of ventilation and APACHE II scores did not undergo pooled analysis due to insufficient data. Exogenous surfactant did not reduce mortality in adults with ARDS in our meta-analysis, and we cannot accurately define whether exogenous surfactant has an effect on oxygenation from the included studies.
PubMed: 23251275
DOI: 10.3892/etm.2012.746 -
Neonatology 2022Surfactant therapy is the cornerstone of respiratory distress syndrome management. "Less-invasive surfactant administration (LISA)" is now recommended for spontaneously...
BACKGROUND
Surfactant therapy is the cornerstone of respiratory distress syndrome management. "Less-invasive surfactant administration (LISA)" is now recommended for spontaneously breathing preterm infants. Analgosedation remains controversial as 52% of European neonatologists do not use any. This systematic review aims to describe the efficacy and safety of different drugs for analgosedation during LISA.
METHODS
MEDLINE via Ovid, Embase, Scopus, and Cochrane Library of Trials were searched independently by 2 reviewers for studies on sedation or analgesia for LISA, without filters or limits.
RESULTS
Eight studies (1 randomized controlled trial) recruiting 945 infants were included. Infant pain was significantly reduced, with more infants evaluated as comfortable. Failure, defined as need for intubation or for a second dose of surfactant, was not different between sedated and unsedated groups. Analgosedation was associated with a higher occurrence of desaturation and need for positive pressure ventilation during procedure, but the need for mechanical ventilation within 24 or 72 h of life was not significantly different. There does not seem to be any difference in clinical tolerance and complications (e.g., hypotension, mortality, air leaks, etc.). Procedural conditions were evaluated as good or excellent in 83% after sedation.
DISCUSSION AND CONCLUSION
Analgesia or sedative drugs increase infant comfort and allow good procedural conditions, with a limited impact on the clinical evolution. Questions remain about the best choice of drugs and dosages, with the constraint to maintain spontaneous breathing and have a rapid offset. Further good quality studies are needed to provide additional evidence to supplement those limited existing data.
Topics: Humans; Infant; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 35124678
DOI: 10.1159/000521553 -
Jornal de Pediatria 2023Among the mechanisms proposed for the development of bronchopulmonary dysplasia is the increase in the pulmonary inflammatory process and oxidative stress. Thus, the... (Review)
Review
OBJECTIVE
Among the mechanisms proposed for the development of bronchopulmonary dysplasia is the increase in the pulmonary inflammatory process and oxidative stress. Thus, the control of this process may result in improvements in bronchopulmonary dysplasia-related outcomes. This study aims to analyze the current scientific evidence regarding the use of budesonide, a potent anti-inflammatory drug, associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia.
METHODS
A systematic review of the literature was performed on the Embase and MEDLINE platforms, and studies that compared budesonide with pulmonary surfactant versus pulmonary surfactant for treating respiratory distress syndrome were included. The primary outcome was a reduction in bronchopulmonary dysplasia or death.
RESULTS
Four randomized clinical trials and two observational studies were included in this systematic review. Three of the randomized clinical trials found a reduction in bronchopulmonary dysplasia or death in the use of budesonide with the surfactant, all the other studies (1 clinical trial and 2 observational studies) found no statistical differences between the groups for the primary outcomes. The three main studies showed a reduction in the primary outcome; however, all studies showed great heterogeneity regarding the type of surfactant (poractant or beractant) and the method of administration.
CONCLUSION
Robust clinical studies, in a heterogeneous population, using porcine surfactant associated with budesonide, with administration by a minimally invasive technique are necessary for there to be a recommendation based on scientific evidence for its widespread use.
Topics: Humans; Animals; Swine; Infant, Newborn; Budesonide; Pulmonary Surfactants; Bronchopulmonary Dysplasia; Respiratory Distress Syndrome, Newborn; Surface-Active Agents; Randomized Controlled Trials as Topic
PubMed: 36436670
DOI: 10.1016/j.jped.2022.10.007 -
Neonatology 2012Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established.
OBJECTIVE
To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis.
METHODS
Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias.
RESULTS
Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta-analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence.
CONCLUSIONS
Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique.
Topics: Biological Products; Bronchoalveolar Lavage; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Phosphatidylglycerols; Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 22067375
DOI: 10.1159/000329822