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Journal of Controlled Release :... Feb 2022The COVID-19 pandemic has wielded an enormous pressure on global health care systems, economics and politics. Ongoing vaccination campaigns effectively attenuate viral... (Review)
Review
The COVID-19 pandemic has wielded an enormous pressure on global health care systems, economics and politics. Ongoing vaccination campaigns effectively attenuate viral spreading, leading to a reduction of infected individuals, hospitalizations and mortality. Nevertheless, the development of safe and effective vaccines as well as their global deployment is time-consuming and challenging. In addition, such preventive measures have no effect on already infected individuals and can show reduced efficacy against SARS-CoV-2 variants that escape vaccine-induced host immune responses. Therefore, it is crucial to continue the development of specific COVID-19 targeting therapeutics, including small molecular drugs, antibodies and nucleic acids. However, despite clear advantages of local drug delivery to the lung, inhalation therapy of such antivirals remains difficult. This review aims to highlight the potential of pulmonary surfactant (PS) in the treatment of COVID-19. Since SARS-CoV-2 infection can progress to COVID-19-related acute respiratory distress syndrome (CARDS), which is associated with PS deficiency and inflammation, replacement therapy with exogenous surfactant can be considered to counter lung dysfunction. In addition, due to its surface-active properties and membrane-interacting potential, PS can be repurposed to enhance drug spreading along the respiratory epithelium and to promote intracellular drug delivery. By merging these beneficial features, PS can be regarded as a versatile biomaterial to combat respiratory infections, in particular COVID-19.
Topics: Antiviral Agents; Biocompatible Materials; COVID-19; Humans; Pandemics; Pulmonary Surfactants; SARS-CoV-2
PubMed: 34813878
DOI: 10.1016/j.jconrel.2021.11.023 -
Biomedical Journal Dec 2021This issue of the Biomedical Journal provides a comprehensive insight into the role of pulmonary surfactant and influencing its components as well as involved molecules...
This issue of the Biomedical Journal provides a comprehensive insight into the role of pulmonary surfactant and influencing its components as well as involved molecules to treat a variety of respiratory distress disorders. We also discover how epithelial mesenchymal transition (EMT) could be targeted as part of a therapeutic strategy against lung cancer. Furthermore, a method is described to eliminate chemoresistance against gemcitabine, a drug administered to treat pancreatic cancer. We gain an insight into the composition of salivary calcium particles in periodontitis, a technique to circumvent complications in hip surgery, and a potential treatment to accelerate diabetic wound healing. Moreover, we get to know an essential oil that exerts a similar effect as diazepam on the central nervous system. A trial in patients with myofascial pain syndrome demonstrates how laser assisted trigger point therapy leads to immediate relief. Finally, a case study outlines the discovery of a genetic mutation that plays a role in intellectual disability.
Topics: Epithelial-Mesenchymal Transition; Humans; Pancreatic Neoplasms; Pulmonary Surfactants; Wound Healing
PubMed: 34942391
DOI: 10.1016/j.bj.2021.12.003 -
Clinics in Perinatology Mar 2022Extremely preterm infants who must suddenly support their own gas exchange with lungs that are incompletely developed and lacking adequate amount of surfactant and... (Review)
Review
Extremely preterm infants who must suddenly support their own gas exchange with lungs that are incompletely developed and lacking adequate amount of surfactant and antioxidant defenses are susceptible to lung injury. The decades-long quest to prevent bronchopulmonary dysplasia has had limited success, in part because of increasing survival of more immature infants. The process must begin in the delivery room with gentle assistance in establishing and maintaining adequate lung aeration, followed by noninvasive support and less invasive surfactant administration. Various modalities of invasive and noninvasive support have been used with varying degree of effect and are reviewed in this article.
Topics: Bronchopulmonary Dysplasia; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Lung; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 35210003
DOI: 10.1016/j.clp.2021.11.019 -
Biomedical Journal Aug 2022The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement... (Review)
Review
The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.
Topics: Animals; Humans; Infant, Newborn; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 35272060
DOI: 10.1016/j.bj.2022.03.001 -
Chest Apr 2023
Topics: Humans; Pulmonary Fibrosis; Surface-Active Agents; Pulmonary Surfactants; Mutation
PubMed: 37031979
DOI: 10.1016/j.chest.2022.12.020 -
BMJ Paediatrics Open Jul 2022To compare outcome after less invasive surfactant administration (LISA) and primary endotracheal intubation (non-LISA) in infants born before gestational age (GA) 28...
OBJECTIVE
To compare outcome after less invasive surfactant administration (LISA) and primary endotracheal intubation (non-LISA) in infants born before gestational age (GA) 28 weeks.
SETTING
All neonatal intensive care units (NICUs) in Norway during 2012-2018.
METHODS
Defined population-based data were prospectively entered into a national registry. We compared LISA infants with all non-LISA infants and with non-LISA infants who received surfactant following intubation. We used propensity score (PS) matching to identify non-LISA infants who were similar regarding potential confounders.
MAIN OUTCOME VARIABLES
Rate and duration of mechanical ventilation (MV), survival, neurological and gastrointestinal morbidity, and need of supplemental oxygen or positive pressure respiratory support at postmenstrual age (PMA) 36 and 40 weeks.
RESULTS
We restricted analyses to GA 25-27 weeks (n=843, 26% LISA) because LISA was rarely used at lower GAs. There was no significant association between NICUs regarding proportions treated with LISA and proportions receiving MV. In the PS-matched datasets, fewer LISA infants received MV (61% vs 78%, p<0.001), and they had fewer days on MV (mean difference 4.1, 95% CI 0.0 to 8.2 days) and lower mortality at PMA 40 weeks (absolute difference 6%, p=0.06) compared with all the non-LISA infants, but only a lower rate of MV (64% vs 97%, p<0.001) and fewer days on MV (mean difference 5.8, 95% CI 0.6 to 10.9 days) compared with non-LISA infants who received surfactant after intubation.
CONCLUSION
LISA reduced the rate and duration of MV but had no other clear benefits.
Topics: Humans; Infant; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Lipoproteins; Noninvasive Ventilation; Propensity Score; Pulmonary Surfactants; Respiration, Artificial; Surface-Active Agents
PubMed: 36053649
DOI: 10.1136/bmjpo-2022-001527 -
Pediatric Pulmonology Oct 2021Various less invasive surfactant administration strategies like surfactant replacement therapy via thin catheters, laryngeal mask airway, pharyngeal instillation, and... (Review)
Review
Various less invasive surfactant administration strategies like surfactant replacement therapy via thin catheters, laryngeal mask airway, pharyngeal instillation, and nebulized surfactant are increasingly being practiced to avoid the harmful effects of endotracheal intubation and ventilation. Numerous studies have been done to study surfactant replacement via thin catheters whereas little data is available for other methods. However, there are variations in premedication policies, type of respiratory support used in these studies. Surfactant delivery using thin catheters has been reported to be associated with decrease in the need for mechanical ventilation (MV), duration of MV, bronchopulmonary dysplasia and neonatal mortality. With the current evidence, among all the available surfactant delivery methods, the one using thin catheters appears to be the most feasible and beneficial to improve clinical neonatal outcomes.
Topics: Bronchopulmonary Dysplasia; Catheters; Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 34379878
DOI: 10.1002/ppul.25599 -
Human Gene Therapy Oct 2022Genetic disorders of surfactant dysfunction result in significant morbidity and mortality, among infants, children, and adults. Available medical interventions are... (Review)
Review
Genetic disorders of surfactant dysfunction result in significant morbidity and mortality, among infants, children, and adults. Available medical interventions are limited, nonspecific, and generally ineffective. As such, the need for effective therapies remains. Pathogenic variants in the , and genes, each of which encode proteins essential for proper pulmonary surfactant production and function, result in interstitial lung disease in infants, children, and adults, and lead to morbidity and early mortality. Expression of these genes is predominantly limited to the alveolar type 2 (AT2) epithelial cells present in the distal airspaces of the lungs, thus providing an unequivocal cellular origin of disease pathogenesis. While several treatment strategies are under development, a gene-based therapeutic holds great promise as a definitive therapy. Importantly for clinical translation, the genes associated with surfactant dysfunction are both well characterized and amenable to a gene-therapeutic-based strategy. This review focuses on the pathophysiology associated with these genetic disorders of surfactant dysfunction, and also provides an overview of the current state of gene-based therapeutics designed to target and transduce the AT2 cells.
Topics: Infant; Child; Adult; Humans; Pulmonary Surfactants; Lung Diseases, Interstitial; Lung; Epithelial Cells; Mutation; Alveolar Epithelial Cells
PubMed: 36166236
DOI: 10.1089/hum.2022.130 -
Seminars in Perinatology Oct 2023Bronchopulmonary dysplasia (BPD) is one of the most devastating morbidities of preterm infants. Antenatal factors like growth restriction and inflammation are risk... (Review)
Review
Bronchopulmonary dysplasia (BPD) is one of the most devastating morbidities of preterm infants. Antenatal factors like growth restriction and inflammation are risk factors for its development. Use of oxygen and positive pressure ventilation, which are often necessary to treat respiratory distress syndrome (RDS), increase the risk for development of BPD. Continuous positive airway pressure (CPAP) as primary respiratory support allows for avoidance of positive pressure ventilation in many cases but may lead to a delay of surfactant administration which is a proven therapy for RDS. Several alternative surfactant delivery strategies, including nebulization of surfactant, pharyngeal instillation of surfactant, delivery of surfactant via supraglottic airway device or surfactant delivery via a thin endotracheal catheter have been described which allow for the benefit of surfactant therapy while on CPAP. This review reports available data and discusses the existing evidence of their value in preventing BPD as well as further research directions.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Infant, Premature; Surface-Active Agents; Bronchopulmonary Dysplasia; Pulmonary Surfactants; Continuous Positive Airway Pressure; Respiratory Distress Syndrome, Newborn
PubMed: 37805275
DOI: 10.1016/j.semperi.2023.151813 -
Archives of Disease in Childhood. Fetal... Jul 2019Pulmonary surfactant (PS) is a lipid-protein complex essential to stabilise the delicate structure of mammalian alveoli along with successive compression-expansion... (Review)
Review
Pulmonary surfactant (PS) is a lipid-protein complex essential to stabilise the delicate structure of mammalian alveoli along with successive compression-expansion respiratory cycles. To do so, surfactant reduces dramatically surface tension at the air-liquid interface, an activity that depends critically on a proper lipid composition and the presence of some specific surfactant proteins. Lack or dysfunction of this system is associated with severe respiratory pathologies, which are in some cases treated by supplementation with exogenous surfactant materials. The biophysical function and performance of PS, in health and disease, are directly influenced by its composition, structure and mechanical properties. This review summarises the main biophysics concepts behind the mechanisms that define surfactant function in a healthy lung and in pathological situations. It also revises some of the most useful biophysical techniques that provide information about surfactant-related processes. Finally, translational biophysics will be invoked to illustrate how biophysical studies may contribute to understand the role of surfactant in health and disease and to design better surfactant-based therapeutic approaches.
Topics: Animals; Biophysical Phenomena; Humans; Lipid Metabolism; Lung; Membrane Fusion; Membrane Lipids; Phospholipids; Pulmonary Surfactants; Surface Tension
PubMed: 30552091
DOI: 10.1136/archdischild-2018-315413