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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 -
Frontiers in Genetics 2019Surfactant protein D (SFTPD) is a lung specific protein which performs several key regulatory processes to maintain overall lung function. Several infectious and immune...
Surfactant protein D (SFTPD) is a lung specific protein which performs several key regulatory processes to maintain overall lung function. Several infectious and immune mediated diseases have been shown to be associated with SFTPD. Recent findings have suggested the serum concentration of SFTPD can be used as a diagnostic or prognostic marker for chronic obstructive pulmonary disease (COPD) and acute exacerbation COPD (AECOPD). But these findings lack replication studies from different ethnic populations and meta-analysis, to establish SFTPD as reliable diagnostic or prognostic biomarker for COPD and associated conditions. We performed systematic literature search based on stringent inclusion and exclusion criteria to identify eligible studies to perform a meta-analysis. Our objective was to assess the predictability of serum SFTPD concentration and SFTPD allelic conformation at rs721917 (C > T) with COPD and AECOPD outcome. These variables were compared between COPD and healthy controls, where mean difference (MD), and odds ratio (OR) were calculated to predict the overall effect size. Review manager (RevMan-v5.3) software was used to analyse the data. A total of eight published reports were included in this study. Comparative serum SFTPD concentration data were extracted from six studies and three studies were evaluated for assessment of genetic marker from SFTPD. Our study identified strong association of elevated serum SFTPD with COPD and AECOPD. Significant association of risk was also observed for "T" allele or "TT" genotype of rs721917 from SFTPD with COPD and AECOPD. Serum concentration and alleleic conformation of SFTPD has a significantly high predictive value for COPD and AECOPD. Thus, these can be tested further and could be applied as a predictive or prognostic marker.
PubMed: 31057601
DOI: 10.3389/fgene.2019.00339 -
Pediatric Pulmonology Jan 2022Less invasive surfactant administration methods without laryngoscopy and endotracheal catheterization include delivery via laryngeal mask airway, pharyngeal... (Review)
Review
Less invasive surfactant administration methods without laryngoscopy and endotracheal catheterization include delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization. These less invasive techniques are promising and have several advantages over INSURE (Intubation-Surfactant-Extubation) and thin catheter techniques. The objective of this review is to discuss the requisites, techniques, short-term outcomes, and adverse events associated with these methods.
Topics: Humans; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Laryngeal Masks; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 34559459
DOI: 10.1002/ppul.25698 -
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 -
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 -
Resuscitation Feb 2023Initial management of inadequate adaptation to extrauterine life relies on non-invasive respiratory support. Two types of devices are available: fixed pressure devices... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Initial management of inadequate adaptation to extrauterine life relies on non-invasive respiratory support. Two types of devices are available: fixed pressure devices (FPD; T-pieces or ventilators) and hand driven pressure devices (HDPD; self- or flow-inflating bags). This systematic review and meta-analysis aims to compare clinical outcomes after neonatal resuscitation according to device type.
METHODS
Four databases were searched from inception to 2022, January. Search strategies included Mesh/Emtree terms as well as free language without any restriction. Randomized, quasi-randomized studies and prospective cohorts comparing the use of the two types of devices in neonatal resuscitation were included.
RESULTS
Nine studies recruiting 3621 newborns were included: 5 RCTs, 2 RCTs with interventions bundles and 2 prospective cohorts. Meta-analysis of the 5 RCTs demonstrated significant reductions in bronchopulmonary dysplasia (RR0,68[0,48-0,96]-NNT 31) and other respiratory outcomes: intubation in the delivery room (RR0,72[0,58-0,88]-NNT 13,4), mechanical ventilation requirements (RR0,81[0,67-0,96]-NNT 17) and duration (MD-1,54 days[-3,03- -0,05]), need for surfactant (RR0,79[0,64-0,96]-NNT 7,3). The overall analysis found a lower mortality in the FPD group (OR0,57[0,47-0,69]-NNT 12,7) and confirmed decreases in intubation, surfactant requirement and mechanical ventilation rates (OR 0,56[0,40-0,79]- NNT7,5; OR 0,67[0,55-0,82]-NNT10,7 and OR0,58[0,42-0,80]- NNT 7,4 respectively). The risk of cystic periventricular leukomalacia (cPVL) decreased significantly with FPD (OR0.59[0.41-0.85]-NNT 27). Pneumothorax rates were similar (OR0.82[0.44-1.52]).
CONCLUSION AND RELEVANCE
Resuscitation at birth with FPD improves respiratory transition and decreases BPD with a very low to moderate certainty of evidence. There is suggestion of decreases in mortality and cPVL. Further studies are still needed to confirm those results.
Topics: Infant, Newborn; Humans; Resuscitation; Infant, Premature; Prospective Studies; Respiration, Artificial; Pulmonary Surfactants; Surface-Active Agents
PubMed: 36623747
DOI: 10.1016/j.resuscitation.2022.109681 -
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 -
The Cochrane Database of Systematic... May 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; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Infant, Premature; Polyethylene Glycols; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 26009996
DOI: 10.1002/14651858.CD000144.pub2 -
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 -
The Cochrane Database of Systematic... Aug 2015Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis. This is an update of a review published in Issue 9, 2012. We did not identify any new studies for inclusion, and our conclusions remain unchanged.
OBJECTIVES
To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Studies (CENTRAL; 2015, Issue 5) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1948 to June week 3, 2015); EMBASE (1974 to June 2015); CINAHL (1982 to June 2015); LILACS (1985 to June 2015); and Web of Science (1985 to June 2015).
SELECTION CRITERIA
We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data, and performed meta-analyses.
MAIN RESULTS
We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies reported no mortality. We judged all three of the included studies to be at low risk or unclear risk across all risk of bias categories; we did not judge any of the studies to be at high risk of bias in any category. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not significantly different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31, 95% CI -6.38 to -0.25 days. After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99, 95% CI -40.10 to -17.87 hours; and MD -1.81, 95% CI -2.42 to -1.19 days, respectively. Use of surfactant had favourable effects on oxygenation and CO2 elimination. No adverse effects and no complications were observed in any of the three included studies. The level of evidence for duration of mechanical ventilation, duration of intensive care unit stay, oxygenation parameters, and carbon dioxide parameters was of moderate quality.
AUTHORS' CONCLUSIONS
Use of surfactant had favourable effects on duration of mechanical ventilation, duration of ICU stay, oxygenation, and CO2 elimination. However, the studies are few and small (n = 79) so available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.
Topics: Bronchiolitis; Child, Preschool; Critical Illness; Humans; Infant; Infant, Newborn; Length of Stay; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Time Factors
PubMed: 26299681
DOI: 10.1002/14651858.CD009194.pub3