Use of budesonide associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia in premature newborns - A systematic review

Abstract 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.

Effects of antenatal dexamethasone and postnatal pulmonary surfactant combined with respiratory support on lung fluid clearance in preterm rabbits / 中华围产医学杂志

Objective:To explore the effects of prenatal dexamethasone (DEX), postnatal pulmonary surfactant (PS) and respiratory support on the lung fluid clearance in premature rabbits at gestational age (GA) of 25-28 d (full term: 31 d) and their relationship with dynamic compliance of respiratory system (Cdyn), pulmonary morphology and other parameters.Methods:In our previous publications, premature rabbits were divided into four groups according to the intervention strategy: control group, PS-only group, DEX-only group and DEX+PS group in which data of several parameters including wet-to-dry lung weight ratio (W/D), Cdyn and volume density of alveoli (Vv) were retrieved and the lung tissue sections were scanned to recalculate the ratio of perivascular sheath to vascular sectional area (S/V) and lung injury scores-edema (LIS-E). W/D, LIS-E, S/V and Vv were adjusted for birth weight (BW) (divided by BW, represented as W/D/BW, LIS-E/BW, S/V/BW and Vv/BW) and mean Cdyn (Cdyn-m) was adopted. Based on the grouping of previous studies, the intervention groups in this study were divided as DEX group and non-DEX group, and PS group and non-PS group to analyze the influence of DEX and PS on the above parameters. Two independent samples t-test, one-way analysis of variance, LSD test, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis were used for statistical analysis. Results:A total of 196 newborn rabbits receiving mechanical ventilation after birth were included in this study. (1) Effects of DEX: compared with the non-DEX group, the DEX group showed increased W/D/BW (489±69 vs 421±113, t=－2.09), LIS-E/BW (188±57 vs 138±55, t=－2.61) and Vv/BW (20.1±4.9 vs 14.2±4.7, t=－3.60), but decreased S/V (0.33±0.23 vs 0.51±0.25, t=2.23) and S/V/W/D (0.05±0.03 vs 0.07±0.04, t=2.22) at 25 d of gestation; at 26 d of gestation, W/D/BW (472±76 vs 303±44, t=－8.75), LIS-E/BW (189±63 vs 106±36, t=－5.23), Cdyn-m [(0.16±0.07) vs (0.05±0.03) ml/(kg?cmH 2O), 1 cmH 2O=0.098 kPa; t=－7.29] and Vv/BW increased (22.4±5.0 vs 12.2±3.8, t=－7.46), while S/V (0.23±0.19 vs 0.62±0.38, t=4.10), S/V/BW (15.7±12.4 vs 25.7±17.3, t=2.20), S/V/W/D (0.03±0.03 vs 0.08±0.05, t=3.92) and propensity scores decreased [(12.5±1.2) vs (15.1±1.2) scores, t=7.00]; at 27 d of gestation, Cdyn-m increased [(0.23±0.12) vs (0.16±0.07) ml/(kg?cmH 2O), t=－2.43], but S/V (0.32±0.23 vs 0.57±0.39, t=2.57) and S/V/W/D decreased (0.05±0.04 vs 0.09±0.06, t=2.55); at 28 d of gestation, W/D/BW (270±64 vs 162±33, t=－8.09), LIS-E/BW (72±32 vs 35±20, t=－5.17), S/V (0.90±0.60 vs 0.59±0.48, t=－2.81), S/V/BW (34.0±23.6 vs 15.2±12.7, t=－3.77) and Vv/BW increased (16.9±4.3 vs 9.2±2.9, t=－8.04); the differences were all statistically significant (all P<0.05). (2) Effects of PS: compared with the non-PS group, the PS group had decreased LIS-E/BW at 25, 26 and 27 d of gestation, increased Cdyn-m and Vv/BW at 25 and 27 d of gestation and higher propensity scores at 25 d of gestation (all P<0.05). (3) The correlation between gestational age and each index: gestational age was positively correlated with S/V ( r=0.31, P<0.05), but negatively correlated with W/D/BW and LIS-E/BW ( r=－0.73 and－0.63, both P<0.05). Conclusions:The pharmacological action of prenatal DEX on lung fluid clearance is mainly confined to preterm rabbits at the GA of 28 d which is supported by mechanical ventilation. Prenatal treatment with DEX and/or postnatal PS can improve the early respiratory function in preterm rabbits between GA of 25-27 d, but had no substantial impact on lung fluid clearance. The GA-related lung maturation appears to play a crucial role, in comparison with medications, in lung fluid clearance.

Efecto de las aguas jabonosas sobre el comportamiento de hemípteros semiacuáticos (Gerromorpha) de dos ecosistemas acuáticos neotropicales / Effect of soapy water on the behavior of semiaquatic hemipterans (Gerromorpha) from two neotropical aquatic ecosystems

Resumen Introducción: Los hemípteros semiacuáticos son insectos que podrían ser de los mejores indicadores de la calidad del ambiente acuático, específicamente en cuanto al contenido de sustancias que rompen la tensión superficial. Sin embargo, no existen estudios que evalúen cómo estos insectos se ven afectados por cambios en la tensión superficial del agua. Objetivo: Determinar el efecto que tienen las aguas jabonosas sobre la capacidad de locomoción de tres especies de hemípteros semiacuáticos neotropicales. Métodos: Desde agosto hasta noviembre 2020, realizamos experimentos ex situ, con nueve grupos de diez individuos de la familia Veliidae (N = 90) y Gerridae (N = 90), en donde cada grupo individualmente, fue sometido a la entrada de aguas jabonosas durante tres minutos. Para esto, diseñamos un acuario que consistía en tres cajas de plástico a diferentes alturas, conectadas entre sí, de modo que se generaba un flujo de corriente. Utilizamos jabón en polvo para ropa, jabón líquido para manos, y jabón en barra para platos. De cada tipo de jabón preparamos una concentración baja (9 ppm), media (50 ppm) y alta (200 ppm). Mediante grabaciones, registramos el tiempo que duraron los hemípteros en el agua, así como su capacidad para salir de la misma, y si se hundían o no. Resultados: Encontramos que, sin importar el tipo de jabón, el tiempo que permanecen los hemípteros en el agua contaminada, se reduce drásticamente conforme aumenta la concentración, pero dicho impacto varía según la especie, siendo Rhagovelia solida (familia Veliidae) menos afectada por la contaminación en comparación con Platygerris caeruleus y Potamobates unidentatus (familia Gerridae). Conclusión: El uso de estos táxones como indicadores del grado de contaminación de los ríos por detergentes y jabones, puede ser muy útil, sobre todo si se toma en cuenta las diferencias de sensibilidad según la familia o género del grupo.

Abstract Introduction: Semiaquatic hemipterans are insects that may be among the best indicators of the quality of the aquatic environment, specifically in terms of the content of substances that break surface tension. However, no studies are evaluating how these insects are affected by changes in the surface tension of the water. Objective: To determine the effect of soapy water on the locomotion ability of three species of neotropical semiaquatic hemipterans. Methods: From August to November 2020, we conducted ex situ experiments, with nine groups of ten individuals of the family Veliidae (N = 90) and Gerridae (N = 90), where each group individually, was subjected to the entry of soapy water for three minutes. For this, we designed an aquarium consisting of three plastic boxes at different heights, connected to each other, so that a current flow was generated. We used powdered laundry soap, liquid hand soap, and bar soap for dishes. For each type of soap we prepared a low (9 ppm), medium (50 ppm) and high (200 ppm) concentration. By means of recordings, we recorded the time the hemipterans spent in the water, as well as their ability to get out of the water, and whether or not they sank. Results: We found that, regardless of the type of soap, the time spent by hemipterans in contaminated water decreases drastically as the concentration increases, but the impact varies by species, with Rhagovelia solida (family Veliidae) being less affected by pollution compared to Platygerris caeruleus and Potamobates unidentatus (family Gerridae). Conclusions: The use of these taxa as indicators of the degree of contamination of rivers by detergents and soaps can be very useful, especially if we take into account the differences in sensitivity according to the family or gender of the group.

Disfunción del transportador del surfactante pulmonar ABCA3: reporte de un caso peruano / Surfactant ABCA3 transporter dysfunction: a case report from Peru

Resumen Introducción: Los trastornos genéticos que afectan la homeostasis del surfactante pulmonar son una causa importante del síndrome de dificultad respiratoria en el recién nacido a término y de enfermedad pulmonar intersticial difusa en niños. El transportador ABCA3 (ATP binding cassette A3) interviene en la producción normal del surfactante que recubre el interior de las paredes alveolares y funciona como agente tensioactivo. Caso clínico: Recién nacido a término que presentó dificultad respiratoria a los 3 días de vida y requirió ventilación mecánica. Los estudios para determinar otras causas de enfermedad pulmonar fueron negativos. Se realizó una biopsia de pulmón para realizar estudios de microscopía óptica y microscopía electrónica. Esta última mostró pequeños cuerpos lamelares anómalos, además de condensaciones electrodensas periféricas, características de las mutaciones del transportador ABCA3. Se inició tratamiento con pulsos de metilprednisolona, hidroxicloroquina, azitromicina y corticoides inhalados a dosis altas, y la respuesta clínica y radiológica fue favorable durante el seguimiento. Conclusiones: La correlación de las características clínicas y de las imágenes (tomografía y microscopía electrónica) puede ser útil para el diagnóstico de la disfunción del surfactante pulmonar, especialmente en los países de bajos y medianos recursos que no disponen de estudios genéticos para determinar las diferentes mutaciones del transportador ABCA3. Este es uno de los primeros casos reportados en Perú con respuesta adecuada al tratamiento y evolución favorable durante el seguimiento.

Abstract Background: Genetic disorders affecting pulmonary surfactant homeostasis are a major cause of respiratory distress syndrome in full-term newborn and childhood interstitial lung disease. The ABCA3 transporter (ATP binding cassette A3) intervenes in the normal production of surfactant that covers the interior of alveolar walls and plays a fundamental role as a surfactant. Case report: Male term newborn who presented respiratory distress 3 days after birth and required mechanical ventilation. Studies to determine other causes of lung disease were negative. Lung biopsy was performed for the study with light microscopy and electron microscopy. Electron microscopy showed small abnormal lamellar bodies in addition to peripheral electrodense condensations characteristic of ABCA3 transporter mutation. Treatment was started with pulses of methylprednisolone, hydroxychloroquine, azithromycin, and high-dose inhaled corticosteroids, finding a favorable clinical and radiological response to follow-up. Conclusions: Correlation of clinical characteristics and images (tomography and electron microscopy) can be useful for the diagnosis of lung surfactant dysfunction, especially in low and medium-income countries where genetic studies to determine the different ABCA3 transporter mutations are not available. This is one of the first cases reported in Peru with an adequate response to treatment and favorable evolution to follow-up.

Production of green surfactants: market prospects

Science has greatly contributed to the advancement of technology and to the innovation of production processes and their applications. Cleaning products have become indispensable in today's world, as personal and environmental hygiene is important to all societies worldwide. Such products are used in the home, in most work environments and in the industrial sectors. Most of the detergents on the market are synthesised from petrochemical products. However, the interest in reducing the use of products harmful to human health and the environment has led to the search for detergents formulated with natural, biodegradable surfactant components of biological (plant or microbiological) origin or chemically synthesised from natural raw materials usually referred to as green surfactants. This review addresses the different types, properties, and uses of surfactants, with a focus on green surfactants, and describes the current scenario as well as the projections for the future market economy related to the production of the different types of green surfactants marketed in the world.

Assessment of the Toxicological Effects of Pesticides and Detergent Mixtures on Zebrafish Gills: a Histological Study

Abstract Pesticides, as Temephos and Roundup, and surfactants, like Sodium Dodecyl Sulfate (SDS), when discharged into the environment, are harmful to non-target wildlife, especially fish. To evaluate the effects of those chemicals alone and their binary combinations, we assessed the histological alterations in Danio rerio gills after 15 days of exposure to Temephos (1ppm), Roundup (10ppm), SDS (2ppm), SDS plus Temephos (2ppm+1ppm), SDS plus Roundup (2ppm+10ppm) and Temephos plus Roundup (1ppm+10ppm). Hyperplasia, a regressive change, was significant in all exposed groups. The progressive change, complete fusion of lamellae, was significantly intensive in Roundup plus Temephos group. Regarding circulatory disturbances, vascular congestion was significant intensive in SDS group, while severe aneurysm was observed in Roundup group. Although xenobiotics in the blend are biologically complex, mainly for long periods, combinatorial exposure incremented only complete fusion of lamellae. Our results reinforce the rationalization of indiscriminate use of those compounds alone or in combination.

Randomized control study on the outcome of less invasive surfactant administration in premature infants / 中国新生儿科杂志

Objective To compare the short-term outcomes of less invasive surfactant administration (LISA) with traditional intubate-surfactant-extubate (INSURE) method for respiratory distress syndrome (RDS) in premature infants.Method From January 2017 to December 2018,premature infants (gestational age ≤32 weeks) diagnosed with RDS who needed pulmonary surfactant (PS) administration were prospectively enrolled and randomly assigned into LISA group and INSURE group.The duration of oxygen supply,side effects during PS administration,the outcome and severe adverse events,bronchopulmonary dysplasia (BPD),necrotizing enterocolitis (NEC),3 ～ 4° periventricular intraventricular hemorrhage (PIVH),periventricular leukomalacia (PVL) and death were compared.Result A total of 67 cases were enrolled including 34 in LISA group and 33 in INSURE group.No significant differences existed between the two group on mechanical ventilation rates,oxygen therapy duration and the incidences of severe adverse events.However,the duration of noninvasive ventilation in LISA group was significantly longer than INSURE group [(10.5 ± 8.7) d vs.(7.1 ± 2.6) d,P ＜ 0.05].The LISA group had significantly higher PS reflux rate than INSURE group [41.2％ (14/34)vs.18.2％ (6/33),P ＜0.05].Conclusion LISA has similar clinical effects and severe adverse events as INSURE,but with higher rates of PS reflux and longer duration of noninvasive ventilation.

Síndrome do desconforto respiratório: influência do manejo sobre o estado hemodinâmico de recém-nascidos pré-termo ≤ 32 semanas nas primeiras 24 horas de vida / Respiratory distress syndrome: influence of management on the hemodynamic status of ≤ 32-week preterm infants in the first 24 hours of life

RESUMO Objetivo: Investigar a influência do manejo da síndrome do desconforto respiratório sobre parâmetros clínicos e ecocardiográficos de avaliação hemodinâmica em recém-nascidos ≤ 32 semanas. Métodos: Foram avaliados prospectivamente 33 recém-nascidos ≤ 32 semanas, submetidos à ventilação mecânica invasiva. A necessidade de surfactante exógeno e os parâmetros clínicos e ecocardiográficos nas primeiras 24 horas de vida foram detalhadas nesse grupo de pacientes. Resultados: O valor da pressão média de vias aéreas foi significativamente maior nos recém-nascidos que necessitaram de inotrópicos [10,8 (8,8 - 23) cmH2O versus 9 (6,2 - 12) cmH2O; p = 0,04]. Houve correlação negativa entre pressão média de vias aéreas e integral velocidade-tempo da artéria pulmonar (r = -0,39; p = 0,026), débito do ventrículo direito (r = -0,43; p = 0,017) e medidas da excursão do plano do anel tricúspide (r = -0,37; p = 0,036). Verificou-se correlação negativa entre o número de doses de surfactante exógeno e: débito de ventrículo direito (r = -0,39; p = 0,028) e a integral velocidade-tempo da artéria pulmonar (r = -0,35; p = 0,043). Conclusão: Nos recém-nascidos ≤ 32 semanas em ventilação mecânica invasiva, elevações de pressão média de vias aéreas e do número de doses de surfactante correlacionam-se com piora da função cardíaca precoce. Aparentemente, o manejo mais agressivo da síndrome do desconforto respiratório contribui para a instabilidade hemodinâmica desses pacientes.

ABSTRACT Objective: To investigate the influence of respiratory distress syndrome management on clinical and echocardiographic parameters used for hemodynamic evaluation in ≤ 32- week newborns. Methods: Thirty-three ≤ 32-week newborns were prospectively evaluated and subjected to invasive mechanical ventilation. The need for exogenous surfactant and clinical and echocardiographic parameters in the first 24 hours of life was detailed in this group of patients. Results: The mean airway pressure was significantly higher in newborn infants who required inotropes [10.8 (8.8 - 23) cmH2O versus 9 (6.2 - 12) cmH2O; p = 0.04]. A negative correlation was found between the mean airway pressure and velocity-time integral of the pulmonary artery (r = -0.39; p = 0.026), right ventricular output (r = -0.43; p = 0.017) and measurements of the tricuspid annular plane excursion (r = -0.37; p = 0.036). A negative correlation was found between the number of doses of exogenous surfactant and the right ventricular output (r = -0.39; p = 0.028) and pulmonary artery velocity-time integral (r = -0.35; p = 0.043). Conclusion: In ≤ 32-week newborns under invasive mechanical ventilation, increases in the mean airway pressure and number of surfactant doses are correlated with the worsening of early cardiac function. Therefore, more aggressive management of respiratory distress syndrome may contribute to the hemodynamic instability of these patients.

Estrategia de desarrollo clínico para la evaluación de la eficacia y seguridad de SURFACEN( / Clinical development strategy for the evaluation of the efficacy and safety of SURFACEN (

RESUMEN Fundamento: el primer reporte de la eficacia de un surfactante pulmonar exógeno en el tratamiento de la enfermedad de membrana hialina data de 1980. A partir de ese hallazgo diferentes grupos de investigadores en todo el mundo dedican sus esfuerzos al desarrollo de surfactantes pulmonares ya sean naturales o sintéticos. Objetivo: desarrollar una estrategia para la evaluación de la eficacia y seguridad de Surfacen® en el tratamiento, que permitiera su registro e introducción a la práctica habitual. Métodos: para demostrar la eficacia y seguridad de Surfacen® en el tratamiento del síndrome de dificultad respiratoria en recién nacidos pretérmino, se realizaron ensayos clínicos y la fármaco-vigilancia. En otras indicaciones como el síndrome de dificultad respiratoria aguda en niños y adultos; se ejecutaron ensayos clínicos (fase II, III y IV). En todos los ensayos se siguió la metodología establecida para cada fase. Resultados: el Surfacen® demostró su eficacia al mejorar la oxigenación, las variables ventilatorias, las radiográficas, la evolución clínica que contribuyó a reducir la mortalidad en recién nacidos pretérmino, con un perfil de seguridad similar al resto de surfactantes pulmonares comercializados a nivel internacional. La terapia con Surfacen® fue eficaz al reducir la mortalidad en niños (esta última no en adultos), demostró ser bien tolerada y segura al notificarse un número reducido de eventos adversos relacionados con su administración. Los días de estancia en las unidades de cuidados intensivos y días de ventilación mecánica no se modificaron con el esquema de tratamiento evaluado. Conclusiones: se registró Surfacen® para las indicaciones terapéuticas estudiadas y se introdujo en la práctica clínica habitual al contribuir a reducir la mortalidad en niños.

ABSTRACT Background: the first report of the efficacy of an exogenous pulmonary surfactant in the treatment of the membrane hyaline illness dates back to 1980. From this finding, different groups of investigators worldwide dedicate their efforts to the development of pulmonary surfactants either natural or synthetic. Objective: to develop a strategy for the evaluation of the efficacy and safety of Surfacen® in the treatment of respiratory distress syndrome that would allow its registration and introduction to normal practice. Methods: to demonstrate the efficacy and safety of Surfacen® in the treatment of RDS in preterm infants, clinical trials and the pharmaco-vigilance were conducted. In other indications such as acute RDS in children and adults; clinical trials (phase II, III and IV) were conducted. In all the trials, the methodology established for each phase was followed. Results: Surfacen® demonstrated its efficacy by improving oxygenation, ventilation variables, radiographic ones, clinical evolution and contributed to reduce mortality in preterm infants, with a safety profile similar to the rest of commercially available pulmonary surfactants internationally. Surfacen® therapy proved to be effective in improving oxygenation, ventilation variables, radiographic, clinical evolution, contributed to reduce mortality in children, (the latter not in adults) and proved to be well tolerated and safe to notify a reduced number of adverse events related to its administration. The days of stay in the intensive care units and days of mechanical ventilation were not modified with the treatment scheme evaluated. Conclusions: Surfacen® was registered for the therapeutic indications studied and introduced in routine clinical practice contributing to reduce mortality in children.

Administración de surfactante profiláctico por vía orofaríngea previo al pinzamiento de cordón umbilical en el recién nacido de muy bajo peso en la maternidad del Hospital Universitario / Prophylactic oropharyngeal surfactant administration before cord clamping in very low birth weight newborns at the University Children Hospital Maternity Department / Administração de surfactante profilático por via orofaríngea antes do clampeamento do cordão umbilical em recém-nascidos de baixo peso extremo na Maternidade do Hospital Pediátrico Universitário

Resumen: En la era de la búsqueda de estrategias ventilatorias mínimamente invasivas, la administración profiláctica de surfactante con técnicas sencillas, que no requieren elevada destreza y que pueden ser realizadas en ámbitos de baja complejidad, deben ser investigadas para potencialmente disminuir la morbilidad y mortalidad del pretérmino. Se reporta el uso de surfactante en la orofaringe de cuatro recién nacidos de muy bajo peso (promedio de peso de 1.236 g y 28 semanas de edad gestacional), y concomitante colocación de presión positiva continua por pieza nasal antes de la primera inspiración extrauterina manteniendo el cordón intacto. No se registraron efectos adversos y la aspiración gástrica posterior demostró que el surfactante fue inspirado a los pulmones del recién nacido. La administración de surfactante orofaríngeo es una técnica innovadora, segura, factible y reproducible. A la vez que minimizamos los riesgos de posible iatrogenia por la técnica utilizada, facilitamos una transición cardiovascular más estable, manteniendo la circulación fetoplacentaria.

Summary: In the era of minimally invasive ventilatory procedures, the prophylactic administration of surfactant using simple techniques that can be performed in low complexity settings, should be researched as a tool to potentially reduce preterm morbidity and mortality. We report the use of oropharyngeal surfactant in 4 very low birth weight newborns (average birth weight 1236g and 28 weeks of gestational age) and of continuous positive airway pressure before the first intrauterine inspiration and keeping an intact umbilical cord. No adverse effects happened, and the aspiration of gastric residual confirmed that surfactant had reached the lungs. The administration of oropharyngeal surfactant is an innovative, safe, feasible and reproducible technique. It minimizes the risks of possible iatrogenesis due to the technique used, and it also facilitates a more stable cardiovascular transition, maintaining the fetus' placental circulation.

Resumo: Na era da procura de técnicas ventilatórias minimamente invasivas, a administração profilática de surfactante utilizando técnicas simples, que não requerem muita destreza e que pode ser realizada em contextos de baixa complexidade, deve ser pesquisada para reduzir potencialmente a morbidade e mortalidade dos pré-termos. Reportamos o uso de surfactante na orofaringe em 4 recém-nascidos com baixo peso ao nascimento (peso médio de 1,236 g e 28 semanas de idade gestacional), e colocação concomitante de pressão positiva contínua por adaptador nasal, antes da primeira inspiração extrauterina e mantendo o cordão umbilical intacto. Não houve efeitos adversos e o aspirado gástrico subsequente mostrou que o surfactante foi inspirado e observado nos pulmões dos recém-nascidos. O surfactante de administração orofaríngea é uma técnica inovadora, segura, viável e reprodutível. Minimiza os riscos iatrogênicos eventuais devido à técnica utilizada, à vez que proporciona uma transição cardiovascular mais estável porque mantém a circulação da placenta fetal.

Proteinosis alveolar pulmonar / Pulmonary alveolar proteinosis an update

La Proteinosis Alveolar Pulmonar (PAP) es una enfermedad poco frecuente, caracterizada por la acumulación de material lipoproteico derivado del surfactante pulmonar al interior de los alvéolos por una falla de depuración de este material por los macrófagos alveolares, siendo la causa más frecuente de esta disfunción la acción bloqueadora producida por anticuerpos anti factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) lo que lleva a un deterioro del intercambio gaseoso. La evolución es variable abarcando desde la resolución espontánea hasta la insuficiencia respiratoria grave y la muerte. Se describen tres formas de PAP: Genética, secundaria y autoinmune (antes primaria o idiopática) siendo esta última la más frecuente en adultos. Clínicamente, se manifiesta por disnea, tos seca e hipoxemia que pueden ser progresivas. En la radiografía de tórax se encuentran opacidades bilaterales y la tomografía computarizada de tórax de alta resolución (TACAR) muestra vidrio esmerilado con sobre posición de engrosamiento septal intra e interlobulillar, patrón conocido como "crazy paving". El diagnóstico se basa en la clínica y en el lavado broncoalveolar con material PAS positivo. La biopsia quirúrgica es confirmatoria. El tratamiento clásico es el lavado pulmonar total (LPT) para remover el contenido alveolar. Otras alternativas son la administración de GM-CSF subcutáneo o inhalado, plasmaferesis y rituximab, cuyos resultados son variables. Diferentes autores han modificado la forma del LPT y combinado los diferentes métodos de tratamiento con el fin de obtener resultados más rápidos y efectivos.

Pulmonary Alveolar Proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant derived lipoproteinaceous material filling the alveoli, secondary to failure of its clearance by macrophages. Most of the patients are adults that have auto antibodies directed to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). The evolution is towards disturbed gaseous exchange with a wide spectrum of disease from spontaneous recovery to death. There are three forms of PAP: genetic, secondary and autoimmune. Symptoms are scarce and patients may present with dyspnea, dry cough and hypoxemia. Chest X ray shows bilateral opacities and thorax CT depicts ground glass opacities surrounded by septal widening, the so called "crazy paving" pattern. Diagnosis is made on clinical and radiological grounds and confirmed by PAS positive staining of bronchoalveolar lavage material or surgical lung biopsy. Accepted treatment is whole lung lavage (WLL) with saline. Alternatives are subcutaneous or inhaled GM-CSF, Plasmapheresis or Rituximab, and even modification of the method of WLL and combination of different manner of treatment.

Ultrasound guided intra-amniotic instillation of pulmonary surfactant combined with ambroxol for prevention of lung injury in preterm rabbits / 中国医学影像技术

Objective: To investigate the value of ultrasound guided intra-amniotic instillation of pulmonary surfactant (PS) combined with prenatal ambroxol hydrochloride (AH) for prevention of lung injury in preterm rabbits. Methods Totally 20 pregnant New Zealand rabbits were randomly divided into 4 groups (each n=5), i.e. ultrasound guided intra-amniotic instillation of PS before cesarean section (PS group), prenatal AH (AH group), ultrasound guided intra-amniotic instillation of PS combined with prenatal AH (PS+AH group) and control group. On the 27th day of pregnancy, rabbit fetuses were removed through cesarean section 1 hour after injection. The survival time of the preterm rabbits, the concentration of interleukin-6 (IL-6) and dipalmitoyl phosphatidylcholine (DPPC) in bronchoalveolar lavage fluid, the expression level of pulmonary surfactant-associated proteins-A (SP-A) in lung tissue were detected. And the lung tissue sections were taken to observe the degree of lung injury. Results: Compared with control group, the survival time of the preterm rabbits of PS group, AH group and PS+AH group prolonged, the concentration of IL-6 decreased, the concentration of DPPC and SP-A increased, and the pathological score of lung injury decreased (all P<0.05). There were significant differences between PS+AH group and PS, AH group in those indexes except for survival time (all P<0.05). Conclusion: Ultrasound guided intra-amniotic instillation of PS combined with prenatal AH plays a role in the prevention of lung injury in preterm rabbits.

Effects of sustained lung inflation combined with pulmonary surfactant on neonatal respiratory distress syndrome: a prospective randomized controlled trial / 中华围产医学杂志

Objective@#To investigate the efficacy and adverse effects of sustained lung inflation (SLI) combined with pulmonary surfactant (PS) in the treatment of neonatal respiratory distress syndrome (NRDS).@*Methods@#This prospective randomized controlled trial included 124 premature infants (gestational age <34 weeks and birth weight <2 000 g) diagnosed with NRDS and in need of PS treatment in Shenzhen Maternity & Child Healthcare Hospital affiliated to Southern Medical University from July 1, 2016 to October 31, 2018. They were randomly divided into experimental or control group, with 62 cases in each. Infants in the experimental group were treated with SLI using T-piece and intratracheal PS, while those in the control group were given PS only. Blood gas analysis and measurement of fraction of inspiration O2 (FiO2) and ratio of partial pressure of oxygen (PO2) over FiO2 were performed before and 1 h after PS injection. Results of the treatments and incidence of complications were compared. Paired samples t-test, two independent samples t-test, rank-sum test and Chi-square test were used for statistical analysis.@*Results@#There were 56 participants in the experimental group and 54 in the control group who were eventually analyzed. In the experimental group, the pH value, partial pressure of carbon dioxide (PCO2), FiO2 and PO2/FiO2 at 1 h after PS injection were all improved compared with those before treatment [pH value: 7.26±0.09 vs 7.19±0.09, t=3.814; PCO2: (51.5±12.6) vs (59.8±16.3) mmHg (1 mmHg=0.133 kPa), t=2.610; FiO2: 26.0 (21.0-31.5)% vs 40.5 (38.5-51.5)%, U=392.000; PO2/FiO2: (284.6±117.9) vs (173.4±59.7) mmHg, t=6.427; all P<0.05]. The overall decrement of FiO2 after PS injection in the experimental group was more significant than that in the control group [-10.0 (-15.0 to -5.0)% vs -5.0 (-8.0 to 0.0)%, U=706.500, P<0.001]. The experimental group had a higher rate of extubation within 24 h than the control group [80% (45/56) vs 71% (32/54), χ2=5.830, P=0.016]. However, no significant differences were shown in total mechanical ventilation time, non-invasive/high-flow nasal cannula ventilation time, the ratio of re-intubation within 72 h, or the incidence of air leak, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, necrotizing enterocolitis or patent ductus arteriosus between the two groups (all P>0.05).@*Conclusions@#SLI combined with PS for NRDS babies can increase the rate of extubation within 24 h and promote the down-regulation of FiO2 without causing significant complications.

Effect of surfactant on respiratory distress syndrome: evaluation by bedside pulmonary ultrasonography / 中国新生儿科杂志

Objective To study the relationship between the lung ultrasonography and the chest X-ray and to study the value of lung ultrasonography score (LUS) in evaluating the effect of pulmonary surfactant (PS) on respiratory distress syndrome (RDS) of newborn.Method Preterm infants admitted to the neonatal intensive care unit of our Hospital from January 2016 to December 2017 and diagnosed with RDS were prospectively studied.LUS examinations were performed prior to,and within the first 6～12 hours after surfactant administration,chest X-rays were also performed at the same time so as to evaluate the effects of surfactant replacement therapy and the correlation between the lung ultrasonography and the chest X-rays.Lung ultrasonography findings at a total of six sites,with three sites in each lung were scored based on the presence of normal finding,the amount of B-lines and subpleural consolidations.Result A total of 45 preterm infants with RDS were enrolled.The cases of X-ray grades Ⅰ,Ⅱ,Ⅲ and Ⅳ before PS administration were 5 cases,21 cases,12 cases and 7 cases respectively.The scores of LUS 0～6,7～12,13～ 18 were 5 cases,37 cases and 3 cases respectively,and the median of LUS was 10 points.Chest X-ray grades Ⅰ,Ⅱ,Ⅲ and Ⅳ within 6～12 hours after PS administration were 18 cases,17 cases,8 cases and 2 cases respectively.LUS of 0～6,7～12,13～18 were 21 cases,20 cases and 4 cases respectively.The median of LUS after PS was 7 points.LUS after PS application was significantly lower than that before PS application (P＜0.001).The LUS was positively correlated with the grades of X-ray before and after surfactant administration (before surfactant administration r =0.688,P＜0.001,after surfactant administration r =0.777,P＜0.001).Conclusion LUS is positively correlated with the grade of chest X-ray and might enable an early detection of the surfactant replacement therapy effects in RDS.Further studies are necessary to define the role of LUS in this field.

A comparative study on LISA and INSURE techniques in preterm neonates with respiratory distress syndrome / 中国新生儿科杂志

Objective To compare the efficacy of less invasive surfactant administration (LISA) and intubation-surfactant-extubation to CPAP (INSURE) techniques in premature infants with respiratory distress syndrome (RDS).Method From January 2016 to January 2017,premature infants with RDS admitted to our hospital were prospectively and randomly assigned into the LISA group and the INSURE group.A 6F suction tube was used to drip pulmonary surfactant (PS) into the trachea with non-invasive respiratory support in the LISA group.INSURE technique and endotracheal intubation with surfactant administration were used in the INSURE group.The following indicators were examined:the time needed for intubation,the change of percutaneous oxygen partial pressure and the incidence of bradycardia during administration,regurgitation after administration,oxygen therapy duration,mechanical ventilation duration,re-administration of PS and apnea.Secondary indicators included the incidences of pneumothorax,pulmonary hemorrhage,neonatal necrotizing enterocolitis (NEC),intraventricular hemorrhage (IVH),bronchopulmonary dysplasia (BPD),preterm retinopathy (ROP),and periventricular leukomalacia (PVL).Result A total of 145 cases were included including 76 in LISA group and 69 in INSURE group.The gestational age was 27～34 weeks.The birth weight was (1 650±480) g.No statistically significant differences existed between the two groups on the time needed for intubation,the change of percutaneous oxygen partial pressure,mechanical ventilation duration,oxygen therapy duration,the incidence of bradycardia,re-administration of PS,apnea and other complications (P＞0.05).Statistically significant differences existed in the incidence of regurgitation (46.1％ in LISA group vs.29.0％ in INSURE group),mechanical ventilation within 72 hours (13.2％ in LISA group vs.27.5％ in INSURE group) and the incidence of BPD (6.6％ in LISA group vs.17.4％ in INSURE group) (P＜0.05).Conclusion Compared with INSURE,LISA technique is effective for the treatment of RDS and reduce invasive ventilation duration and the occurrence of BPD.

History of Pulmonary Surfactant Replacement Therapy for Neonatal Respiratory Distress Syndrome in Korea

Neonatal respiratory distress syndrome (RDS) is a disease that is unique to newborn infants. It is caused by a deficiency of pulmonary surfactant (PS), which is usually ready to be activated around the perinatal period. Until RDS was more clearly understood, it was not known why premature infants died from respiratory failure, although pathology revealed hyaline membranes in the alveoli. Surprisingly, the era of PS replacement therapy began only relatively recently. The first clinical trial investigating neonatal RDS was conducted in 1980. Since then, newborn survival has improved dramatically, which has led to significant advances in the field of neonatology. The present comprehensive review addresses PS, from its discovery to the application of artificial PS in newborns with RDS. It also reviews the history of PS in Korea, including its introduction, various commercial products, present and past research, newborn registries, and health insurance issues. Finally, it describes the inception of the Korean Society of Neonatology and future directions of research and treatment.

Surfactant preparations for preterm infants with respiratory distress syndrome: past, present, and future / 소아과

Following the first successful trial of surfactant replacement therapy for preterm infants with respiratory distress syndrome (RDS) by Fujiwara in 1980, several animal-derived natural surfactants and synthetic surfactants have been developed. Synthetic surfactants were designed to overcome limitations of natural surfactants such as cost, immune reactions, and infections elicited by animal proteins contained in natural surfactants. However, first-generation synthetic surfactants that are protein-free have failed to prove their superiority over natural surfactants because they lack surfactant protein (SP). Lucinactant, a second-generation synthetic surfactant containing the SP-B analog, was better or at least as effective as the natural surfactant, suggesting that lucinactant could act an alternative to natural surfactants. Lucinactant was approved by the U. S. Food and Drug Administration in March 2012 as the fifth surfactant to treat neonatal RDS. CHF5633, a second-generation synthetic surfactant containing SP-B and SP-C analogs, was effective and safe in a human multicenter cohort study for preterm infants. Many comparative studies of natural surfactants used worldwide have reported different efficacies for different preparations. However, these differences are believed to due to site variations, not actual differences. The more important thing than the composition of the surfactant in improving outcome is the timing and mode of administration of the surfactant. Novel synthetic surfactants containing synthetic phospholipid incorporated with SP-B and SP-C analogs will potentially represent alternatives to natural surfactants in the future, while improvement of treatment modalities with less-invasive or noninvasive methods of surfactant administration will be the most important task to be resolved.

Prevalence and factors associated with surfactant use in Brazilian Neonatal Intensive Care Units: A multilevel analysis / Prevalência e fatores associados ao uso de surfactante em unidades de Terapia Intensiva Neonatais brasileiras: análise multinível

Abstract The treatment with exogenous surfactant reduces mortality and the risk of complications in preterm newborns with Respiratory Distress Syndrome. Higher usage levels have been associated with individual and institutional factors. The study aimed to identify these factors associated with use of this technology in 16 public Brazilian Neonatal Units using logistic multilevel analysis. In a sample of 630 newborns the use at some time was 82.6%. Only 24.7% made use of this technology up to two hours after birth. An intraclass correlation of 0.30 showed that 30% of the variance in the use of exogenous surfactant could be assigned to the contextual level. In the final model, a greater severity score (SNAPPE-II) was associated with increased surfactant use (OR = 2.64), whereas being small for gestational age (SGA) (OR = 0.59) was associated with lower use of this technology. At the contextual level the number of beds in the unit >15 (OR = 5.86), units with higher complexity (OR = 1.73) or units with implemented Kangaroo Mother Care (OR = 2.91), especially units in Rio de Janeiro state (OR = 16.17) were associated with greater surfactant use. Although individual clinical features explained most of the variation in the use of this technology, factors linked to the institution were also of utmost importance.

Resumo O tratamento com surfactante exógeno reduz a mortalidade e o risco de complicações em recém-nascidos com Síndrome de Angústia Respiratória. Maiores níveis de utilização dessa tecnologia têm sido associados tanto a fatores individuais como institucionais. O estudo teve como objetivo identificar esses fatores em 16 unidades neonatais públicas brasileiras usando análise multinível. De 630 recém-nascidos, 82,6% usaram a tecnologia em algum momento. Apenas 24,7% fizeram uso até duas horas após o nascimento. Uma correlação intraclasse de 0,30 mostrou que 30% da variação no uso podem ser atribuídos ao nível contextual. No modelo final, um escore de gravidade maior (SNAPPE-II) foi associado com aumento do uso de surfactante (OR = 2,64), enquanto que ser pequeno para a idade gestacional (PIG) (OR = 0,59) foi associado a um menor uso dessa tecnologia. No nível contextual o número de leitos na unidade > 15 (OR = 5,86), as unidades com mais alta complexidade (OR = 1,73) ou unidades com Método Canguru implementado (OR = 2,91), especialmente unidades no estado do Rio de Janeiro (OR = 16,17), foram associados com uma maior utilização de surfactante. Embora características individuais tenham explicado a maior parte da variação no uso desta tecnologia, fatores ligados à instituição também foram de extrema importância.

Transient intubation for surfactant administration in the treatment of respiratory distress syndrome in extremely premature infants / 소아과

PURPOSE: To investigate the effectiveness of transient intubation for surfactant administration and extubated to nasal continuous positive pressure (INSURE) for treatment of respiratory distress syndrome (RDS) and to identify the factors associated with INSURE failure in extremely premature infants. METHODS: Eighty-four infants with gestational age less than 28 weeks treated with surfactant administration for RDS for 8 years were included. Perinatal and neonatal characteristics were retrospectively reviewed, and major pulmonary outcomes such as duration of mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) plus death at 36-week postmenstrual age (PMA) were compared between INSURE (n=48) and prolonged MV groups (n=36). The factors associated with INSURE failure were determined. RESULTS: Duration of MV and the occurrence of BPD at 36-week PMA were significantly lower in INSURE group than in prolonged MV group (P < 0.05), but BPD plus death at 36-week PMA was not significantly different between the 2 groups. In a multivariate analysis, a reduced duration of MV was only significantly associated with INSURE (P=0.001). During the study period, duration of MV significantly decreased over time with an increasing rate of INSURE application (P < 0.05), and BPD plus death at 36-week PMA also tended to decrease over time. A low arterial-alveolar oxygen tension ratio (a/APO2 ratio) was a significant predictor for INSURE failure (P=0.001). CONCLUSION: INSURE was the noninvasive ventilation strategy in the treatment of RDS to reduce MV duration in extremely premature infants with gestational age less than 28 weeks.

Effects of surfactants on water solubility and anti-hepatic fibrosis of curcuminoids / 中草药

Objective To increase the water solubility of curcumin constituents by three kinds of food grade surfactants, and to study the effect of surfactants on the quality standard and stability and anti-hepatic fibrosis in vivo of curcumin solution. Methods The high-speed dispersion method was used to prepare the solution of curcuminoids-surfactants. The qualitative analysis of curcuminoids was confirmed by LC-MS/MS. HPLC-DAD fingerprinting was established and quantitative analysis was conducted. And the effects on anti-liver fibrosis of different concentrations curcumin ratio solution were evaluated by rat model. Results The maximum water solubility of curcumin constituents was 1.387 mg/mL. LC-MS/MS analysis showed that the structure of curcuminoids were stable; The results of fingerprinting analysis demonstrated that the similarity of 18 batches of samples were higher than 99%. The contents of curcumin, demethoxycurcumin and bisdemethoxycurcumin in different batches of samples were stable with the RSD of 1.60%, 2.24%, and 3.74%. The rat model of hepatic fibrosis showed that the contents of AST and ALT in free curcumin suspension group were (64.1 ± 20.3) and (45.1 ± 13.9) U/L, respectively, while that solution of curcuminoids-surfactants group was (19.4 ± 8.7) and (11.8 ± 4.9) U/L. Conclusion The solubility of curcuminoids was increased 517 times compared with the free state (2.677 μg/mL) after solubilization with surfactants, and repeated tests indicated that the structure and contents of curcuminoids were stable; the solubilized curcuminoids exhibited better anti-liver fibrosis effects than the free.