-
Seminars in Fetal & Neonatal Medicine Dec 2023Lung surfactant is the first drug so far designed for the special needs of the newborn. In 1929, Von Neergard described lung hysteresis and proposed the role of surface... (Review)
Review
Lung surfactant is the first drug so far designed for the special needs of the newborn. In 1929, Von Neergard described lung hysteresis and proposed the role of surface forces. In 1955-1956, Pattle and Clements found direct evidence of lung surfactant. In 1959, Avery discovered that the airway's lining material was not surface-active in hyaline membrane disease (HMD). Patrick Bouvier Kennedy's death, among half-million other HMD-victims in 1963, stimulated surfactant research. The first large surfactant treatment trial failed in 1967, but by 1973, prediction of respiratory distress syndrome using surfactant biomarkers and promising data on experimental surfactant treatment were reported. After experimental studies on surfactant treatment provided insight in lung surfactant biology and pharmacodynamics, the first trials of surfactant treatment conducted in the 1980s showed a striking amelioration of severe HMD and its related deaths. In the 1990s, the first synthetic and natural surfactants were accepted for treatment of infants. Meta-analyses and further discoveries confirmed and extended these results. Surfactant development continues as a success-story of neonatal research.
Topics: Infant, Newborn; Humans; Hyaline Membrane Disease; Surface-Active Agents; Respiratory Distress Syndrome, Newborn; Pulmonary Surfactants; Lipoproteins
PubMed: 38030434
DOI: 10.1016/j.siny.2023.101493 -
Frontiers in Immunology 2022
Topics: Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Immunity, Innate; Surface-Active Agents
PubMed: 36582248
DOI: 10.3389/fimmu.2022.1113210 -
American Journal of Physiology. Lung... Feb 2022By coating the alveolar air-liquid interface, lung surfactant overwhelms surface tension forces that, otherwise, would hinder the lifetime effort of breathing. Years of...
By coating the alveolar air-liquid interface, lung surfactant overwhelms surface tension forces that, otherwise, would hinder the lifetime effort of breathing. Years of research have provided a picture of how highly hydrophobic and specialized proteins in surfactant promote rapid and efficient formation of phospholipid-based complex three-dimensional films at the respiratory surface, highly stable under the demanding breathing mechanics. However, recent evidence suggests that the structure and performance of surfactant typically isolated from bronchoalveolar lung lavages may be far from that of nascent, still unused, surfactant as freshly secreted by type II pneumocytes into the alveolar airspaces. In the present work, we report the isolation of lung surfactant from human amniotic fluid (amniotic fluid surfactant, AFS) and a detailed description of its composition, structure, and surface activity in comparison to a natural surfactant (NS) purified from porcine bronchoalveolar lavages. We observe that the lipid/protein complexes in AFS exhibit a substantially higher lipid packing and dehydration than in NS. AFS shows melting transitions at higher temperatures than NS and a conspicuous presence of nonlamellar phases. The surface activity of AFS is not only comparable with that of NS under physiologically meaningful conditions but displays significantly higher resistance to inhibition by serum or meconium, agents that inactivate surfactant in the context of severe respiratory pathologies. We propose that AFS may be the optimal model to study the molecular mechanisms sustaining pulmonary surfactant performance in health and disease, and the reference material to develop improved therapeutic surfactant preparations to treat yet unresolved respiratory pathologies.
Topics: 2-Naphthylamine; Amniotic Fluid; Animals; Calorimetry, Differential Scanning; Humans; Hydrophobic and Hydrophilic Interactions; Laurates; Lipids; Membranes; Pulmonary Surfactants; Swine
PubMed: 34851730
DOI: 10.1152/ajplung.00230.2021 -
Biophysical Journal Aug 2023Liquid ventilation is a mechanical ventilation technique in which the entire or part of the lung is filled with oxygenated perfluorocarbon (PFC) liquids rather than air...
Liquid ventilation is a mechanical ventilation technique in which the entire or part of the lung is filled with oxygenated perfluorocarbon (PFC) liquids rather than air in conventional mechanical ventilation. Despite its many ideal biophysicochemical properties for assisting liquid breathing, a general misconception about PFC is to use it as a replacement for pulmonary surfactant. Because of the high PFC-water interfacial tension (59 mN/m), pulmonary surfactant is indispensable in liquid ventilation to increase lung compliance. However, the biophysical function of pulmonary surfactant in liquid ventilation is still unknown. Here, we have studied the adsorption and dynamic surface activity of a natural surfactant preparation, Infasurf, at the PFC-water interface using constrained drop surfactometry. The constrained drop surfactometry is capable of simulating the intra-alveolar microenvironment of liquid ventilation under physiologically relevant conditions. It was found that Infasurf adsorbed to the PFC-water interface reduces the PFC-water interfacial tension from 59 mN/m to an equilibrium value of 9 mN/m within seconds. Atomic force microscopy revealed that after de novo adsorption, Infasurf forms multilayered structures at the PFC-water interface with an average thickness of 10-20 nm, depending on the adsorbing surfactant concentration. It was found that the adsorbed Infasurf film is capable of regulating the interfacial tension of the PFC-water interface within a narrow range, between ∼12 and ∼1 mN/m, during dynamic compression-expansion cycles that mimic liquid ventilation. These findings have novel implications in understanding the physiological and biophysical functions of the pulmonary surfactant film at the PFC-water interface, and may offer new translational insights into the development of liquid ventilation and liquid breathing techniques.
Topics: Pulmonary Surfactants; Liquid Ventilation; Surface-Active Agents; Surface Tension; Fluorocarbons; Water
PubMed: 37353933
DOI: 10.1016/j.bpj.2023.06.014 -
The Journal of Antimicrobial... Feb 2022Optimizing antifungal therapy is important to improve outcomes in severely immunocompromised patients.
BACKGROUND
Optimizing antifungal therapy is important to improve outcomes in severely immunocompromised patients.
OBJECTIVES
We analysed the in vitro interaction between pulmonary surfactant and antifungal agents used for management of invasive pulmonary aspergillosis.
METHODS
Amphotericin B formulations, mould-active triazoles and echinocandins were tested in vitro against 24 clinical isolates of different Aspergillus spp. with and without the addition of a commercial porcine surfactant (Curosurf®; Poractant alfa, Nycomed, Austria). The data are presented as MIC or minimum effective concentration (MEC) ranges, as MIC or MEC values that inhibited 90% of the isolates (MIC90 or MEC90) and as geometric mean (GM) MIC or MEC values.
RESULTS
For amphotericin B products, addition of surfactant to a final concentration of 10% led to a statistically significant reduction of the GM MIC for all Aspergillus isolates tested after 24 h (0.765 versus 0.552 mg/L; P < 0.05). For the mould-active triazoles, addition of 10% surfactant resulted in a significantly higher GM MIC at 48 h (0.625 versus 0.898 mg/L; P < 0.05). For the echinocandins, the addition of 10% surfactant led to a significantly higher GM MEC after both 24 h (0.409 versus 0.6532 mg/L; P < 0.01) and 48 h (0.527 versus 0.9378 mg/L; P < 0.01). There were no meaningful differences between individual members of the three existing classes of antifungal agents or between the different Aspergillus spp. tested.
CONCLUSIONS
Using EUCAST methodology, addition of porcine surfactant up to a concentration of 10% had a minor, and presumably non-relevant, impact on the in vitro activity of antifungal agents used in prophylaxis and treatment of invasive pulmonary aspergillosis.
Topics: Animals; Antifungal Agents; Aspergillosis; Humans; Invasive Fungal Infections; Microbial Sensitivity Tests; Pulmonary Surfactants; Swine
PubMed: 34788449
DOI: 10.1093/jac/dkab422 -
The Journal of Maternal-fetal &... Dec 2023Respiratory distress syndrome (RDS) is a common critical lung disease in newborn infants, especially those in premature infants with higher mortality rate. Early and...
Respiratory distress syndrome (RDS) is a common critical lung disease in newborn infants, especially those in premature infants with higher mortality rate. Early and correct diagnosis is the key to improve its prognosis. Previously, the diagnosis of RDS mainly relied on chest X-ray (CXR) findings, and it has been graded into four stages based on the progression and severity of CXR changes. This traditional diagnosing and grading method may lead to high misdiagnosis rate or delayed diagnosis. Recently, using ultrasound to diagnose neonatal lung diseases and RDS is becoming increasingly popular, and the technology is gaining higher sensitivity and higher specificity. The management of RDS under lung ultrasound (LUS) monitoring has achieved significant results, reducing the misdiagnosis rate of RDS, thereby reducing the probability of mechanical ventilation and the use of exogenous pulmonary surfactant, and making the success rate of treatment of RDS up to 100%. The purpose of the article was to introduce the ultrasound grading methods and criteria of RDS, in order to promote the application of LUS in the diagnosis and treatment of RDS. Literature (in English and Chinese) on the use of ultrasound in the diagnosis of neonatal RDS between 2008 and 2022 was selected for inclusion in this study. From the collected literature, the use of ultrasound in the diagnosis of RDS is increasing, and people's understanding of the ultrasound imaging findings of RDS is also changing. Among them, the research on ultrasound grading of RDS is the latest progress. Ultrasound is accurate and reliable in the diagnosis and differential diagnosis of RDS. It is of great clinical value to master the ultrasound diagnosis and grading criteria of RDS.
Topics: Infant, Newborn; Humans; Respiratory Distress Syndrome, Newborn; Lung; Infant, Premature; Pulmonary Surfactants; Lung Diseases; Ultrasonography
PubMed: 37142428
DOI: 10.1080/14767058.2023.2206943 -
Respiratory Physiology & Neurobiology Jun 2021Several pre-clinical and clinical trials show that exogenous pulmonary surfactant has clinical efficacy in inflammatory lung diseases, especially ARDS. By infecting type... (Review)
Review
Several pre-clinical and clinical trials show that exogenous pulmonary surfactant has clinical efficacy in inflammatory lung diseases, especially ARDS. By infecting type II alveolar cells, COVID-19 interferes with the production and secretion of the pulmonary surfactant and therefore causes an increase in surface tension, which in turn can lead to alveolar collapse. The use of the pulmonary surfactant seems to be promising as an additional therapy for the treatment of ARDS. COVID-19 causes lung damage and ARDS, so beneficial effects of surfactant therapy in COVID-19-associated ARDS patients are conceivable, especially when applied early in the treatment strategy against pulmonary failure. Because of the robust anti-inflammatory and lung protective efficacy and the current urgent need for lung-supportive therapy, the exogenous pulmonary surfactant could be a valid supportive treatment of COVID-19 pneumonia patients in intensive care units in addition to the current standard of ARDS treatment.
Topics: Administration, Inhalation; Biological Products; COVID-19; Humans; Peptides, Cyclic; Phospholipids; Pulmonary Surfactants; Respiratory Distress Syndrome; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33657448
DOI: 10.1016/j.resp.2021.103645 -
Seminars in Fetal & Neonatal Medicine Dec 2023
Topics: Infant, Newborn; Infant; Humans; Surface-Active Agents; Pulmonary Surfactants; Infant, Premature; Lipoproteins; Respiratory Distress Syndrome, Newborn
PubMed: 38030437
DOI: 10.1016/j.siny.2023.101502 -
The Lancet. Child & Adolescent Health Apr 2020Surfactant is a cornerstone of neonatal critical care, and the presumed less (or minimally) invasive techniques for its administration have been proposed to reduce... (Review)
Review
Surfactant is a cornerstone of neonatal critical care, and the presumed less (or minimally) invasive techniques for its administration have been proposed to reduce invasiveness of neonatal critical care interventions. These techniques are generally known as less invasive surfactant administration (LISA) and have quickly gained popularity in some neonatal intensive care units. Despite the increase in the use of LISA, we believe that the pathobiological background supporting its possible clinical benefits is unclear. Similarly, it is unclear whether there are any ignored drawbacks, as LISA has been tested in only a few trials and some physiopathological issues seem to have gone unnoticed. Active research is warranted to fill these knowledge gaps before LISA can be firmly recommended. In this Viewpoint, we provide an in-depth analysis of LISA techniques, based on physiological and pathobiological factors, followed by a critical appraisal of available clinical data, and highlight some possible future research directions.
Topics: Airway Resistance; Humans; Infant, Newborn; Intensive Care, Neonatal; Intubation, Intratracheal; Laryngoscopy; Lung Diseases, Interstitial; Meta-Analysis as Topic; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome, Newborn
PubMed: 32014122
DOI: 10.1016/S2352-4642(19)30405-5 -
Science China. Life Sciences Jan 2022Pulmonary surfactant is a lipid-protein complex secreted by alveolar type II epithelial cells and is essential for the maintenance of the delicate structure of mammalian...
Pulmonary surfactant is a lipid-protein complex secreted by alveolar type II epithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier. The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking. However, the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear. In the present study, deletion of GM130, which encodes for a matrix protein of the cis-Golgi cisternae, was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids. Specifically, the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum, Sftpb and Sftpc accumulation in the Golgi apparatus, and an increase in the compensatory secretion of Sftpd. Moreover, global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy; however, surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice. Therefore, our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.
Topics: Animals; Autoantigens; Golgi Apparatus; Lung; Membrane Proteins; Mice; Mice, Knockout; Pulmonary Alveoli; Pulmonary Surfactants
PubMed: 33740186
DOI: 10.1007/s11427-020-1875-x