Efficacy and safety of intratracheal administration of budesonide combined with pulmonary surfactant in preventing bronchopulmonary dysplasia: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of early intratracheal administration of budesonide combined with pulmonary surfactant (PS) in preventing bronchopulmonary dysplasia (BPD).@*METHODS@#A prospective randomized controlled trial was designed. A total of 122 infants with a high risk of BPD who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January to July 2021 were enrolled. The infants were randomly divided into a conventional treatment group with 62 infants (treated with PS alone at an initial dose of 200 mg/kg, followed by a dose of 100 mg/kg according to the condition of the infant) and an observation group with 60 infants (treated with PS at the same dose as the conventional treatment group, with the addition of budesonide 0.25 mg/kg for intratracheal instillation at each time of PS application). The two groups were compared in terms of the times of PS use, ventilator parameters at different time points, oxygen inhalation, incidence rate and severity of BPD, incidence rate of complications, and tidal breathing pulmonary function at the corrected gestational age of 40 weeks.@*RESULTS@#Compared with the conventional treatment group, the observation group had a significantly lower proportion of infants using PS for two or three times (P<0.05). Compared with the conventional treatment group, the observation group had a significantly lower fraction of inspired oxygen at 24 and 48 hours and 3, 7, and 21 days after administration, significantly shorter durations of invasive ventilation, noninvasive ventilation, ventilator application, and oxygen therapy, a significantly lower incidence rate of BPD, and a significantly lower severity of BPD (P<0.05). There was no significant difference in the incidence rate of glucocorticoid-related complications between the two groups (P>0.05).@*CONCLUSIONS@#Compared with PS use alone in preterm infants with a high risk of BPD, budesonide combined with PS can reduce repeated use of PS, lower ventilator parameters, shorten the duration of respiratory support, and reduce the incidence rate and severity of BPD, without increasing the incidence rate of glucocorticoid-related complications.

Retratamento com surfactante em prematuros de muito baixo peso: preditores de risco e sua influência nos resultados neonatais / Retreatment with surfactant in very low birth weight preterm infants: risk predictors and their influence on neonatal outcomes

ABSTRACT Objective: To assess clinical predictors and outcomes associated to the need for surfactant retreatment in preterm infants. Methods: Retrospective cohort study, including very low birth weight preterm infants from January 2006 to December 2015 who underwent surfactant replacement therapy. Beractant was used (100 mg/kg), repeated every six hours if FiO2 ≥0.40. The subjects were classified into two groups: single surfactant dose; and more than one dose (retreatment). We evaluated maternal and neonatal predictors for the need of retreatment and neonatal outcomes associated to retreatment. Results: A total of 605 patients (44.5%) received surfactant; 410 (67.8%) one dose, and 195 (32.2%) more than one dose: 163 (83.5%) two doses and 32 (16.4%) three doses. We could not find clinical predictors for surfactant retreatment. Retreatment was associated to a greater chance of BPD in infants >1000 g (RR 1.78; 95%CI 1.30‒2.45) and ≤1000 g (RR 1.33; 95%CI 1.04‒1.70), in infants with gestational age<28 weeks (RR 1.56; 95%CI 1.12‒2.18) and ≥28 weeks (RR 1.50; 95%CI 1.17‒1.92), in neonates with early sepsis (RR 1.48; 95%CI 1.20‒1.81), and in infants not exposed to antenatal corticosteroids (RR 1.62; 95%CI 1.20‒2.17) Conclusions: We could not find predictor factors associated to surfactant retreatment. The need for two or more doses of surfactant was significantly related to bronchopulmonary dysplasia.

RESUMO Objetivo: Avaliar preditores clínicos e resultados associados à necessidade de retratamento com surfactante. Métodos: Coorte retrospectiva com prematuros de muito baixo peso, no período de janeiro de 2006 a dezembro de 2015, em uso de terapia de reposição de surfactante. O surfactante utilizado foi beractante (100 mg/kg), repetido a cada seis horas se FiO2≥0.40. Foram analisados dois grupos: dose única de surfactante e mais de uma dose (retratamento). Foram avaliados preditores maternos e neonatais para retratamento e resultados neonatais. Resultados: 605 pacientes (44,5%) receberam surfactante; 410 (67,8%) uma dose e 195 (32,2%) mais de uma dose: 163 (83,5%) duas doses e 32 (16.4%) três doses. Não foram encontrados fatores associados ao retratamento com surfactante. A displasia broncopulmonar (DBP) foi associada ao retratamento (p<0.01). A presença de retratamento aumentou a chance de ocorrência de DBP em neonatos >1000 g (RR 1,78; IC95% 1,30‒2,45) e ≤1000 g (RR 1,33; IC95% 1,04‒1,70), em recém-nascidos com idade gestacional <28 semanas (RR 1,56; IC95% 1,12‒218) e ≥28 semanas (RR 1,50; IC95% 1,17‒1,92), naqueles com sepse precoce (RR 1,48; IC95% 1,20‒1,81), e nos que não foram expostos ao corticoide antenatal (RR 1,62; IC95% 1,20‒2,17). Conclusões: Não encontramos fatores preditores associados à necessidade de retratamento. A necessidade de duas ou mais doses de surfactante está associada à displasia broncopulmonar.

Comparison of the composition and content of pulmonary surfactant among plateau zokors, plateau pikas and rats / 生理学报

In the present study, the composition and content of pulmonary surfactant (PS) were analyzed to explore the hypoxia adaptation mechanism in plateau zokors (Myospalax baileyi) and plateau pikas (Ochotona curzoniae). 36 plateau zokors and plateau pikas were trapped alive at the Laji Mountain in Guide County, Qinghai Province (at the altitude of about 3 600 m), and 36 Sprague-Dawley (SD) rats were purchased from the experimental animal center of Lanzhou University (at the altitude of about 1 500 m). All animals were lavaged after laboratory anesthesia, the blood in lung tissues was fully washed out and the lung tissues were then taken out to obtain the bronchoalveolar lavage fluid by bronchoalveolar lavage. The composition and content of phospholipids in the PS of three different kinds of animals were analyzed by using high performance liquid chromatography; the protein composition, content and types in the PS were analyzed by G-250 Coomassie brilliant blue method, polyacrylamide gel electrophoresis (PAGE) and mass spectrometry; the dissolved oxygen in the PS solutions were determined by using dissolved oxygen electrode. The results showed that the total contents of phospholipids in the PS were successively increased among plateau zokors, plateau pikas and SD rats (P 0.05). The relative content of PSe had no significant differences between plateau zokors and plateau pikas (P > 0.05), but both were significantly higher than that of SD rats (P < 0.01). The serum albumin (SA) was identified in the PS of three kinds of animals, including homologous tetramer protein containing heme, which is composed of hemoglobin β subunit, in plateau zokors and plateau pikas. Immunoglobulin (Ig) heavy chain was found in PS of plateau zokors and SD rats. The content of Ig heavy chain in plateau zokor was significantly higher than that in SD rats (P < 0.01), and the content of protein containing heme was significantly higher than that in plateau pikas (P < 0.05). The amount of dissolved oxygen was successively decreased in the PS among plateau zokors, plateau pikas and SD rats (P < 0.01), but it was significantly higher than that in saline (P < 0.01). These results suggest that the total content of proteins in the PS of plateau zokors and plateau pikas was significantly higher, while the total content of phospholipids was significantly decreased. There were high content of homologous tetramer protein containing heme in the PS of plateau zokors and plateau pikas. The relative content of DPPC, the main component of phospholipids, was significantly increased in plateau zokors. The changes of PS component and content improve the adaptability of the two plateau animals in hypoxia environment.

Surfactant in SARS-CoV-2 ­ a therapeutic option based on underlying lung cell damage? / Surfactante em SARS-CoV-2 ­ uma opção terapêutica baseada no dano celular subjacente aos pneumócitos?

Introduction: the severe acute respiratory syndrome ­ coronavirus 2 (SARS Cov-2), leads to a diffuse alveolar deterioration due infection of type II pneumocytes. The type II pneumocytes are involved in synthesis and secretion of pulmonary surfactant in pulmonary alveoli. Objective: the purpose of this study is to discuss the indication of surfactant replacement as a potential adjunctive treatment modality for SARS CoV-2, similarly treatment to neonatal respiratory distress syndrome. Methodology: we argue that SARS can be triggered by surfactant deficiency secondary to production deficiency determined by type 2 pneumocyte injuries. In this sense, we carried out a bibliographic review. Conclusion: thus, the replacement of human surfactant could be a potential treatment modality for SARS CoV-2, in the same way that it is indicated for the treatment of neonatal respiratory distress syndrome.

Introdução: a síndrome respiratória aguda grave ­ coronavírus 2 (SARS Cov-2), leva a uma deterioração alveolar difusa devido à infecção do pneumócitos tipo II. Os pneumócitos tipo II estão envolvidos na síntese e secreção de surfactante pulmonar nos alvéolos pulmonares. Objetivo: o objetivo deste estudo é discutir a indicação de reposição de surfactante como uma potencial modalidade de tratamento adjuvante para SARS CoV-2, similarmente ao tratamento da síndrome do desconforto respiratório neonatal. Metodologia: argumentamos que a SARS pode ser desencadeada pela deficiência de surfactante, secundária à deficiência da sua produção determinada por lesões de pneumócitos tipo 2. Nesse sentido, realizamos uma revisão bibliográfica. Conclusão: o uso de surfactante humana pode ser uma potencial modalidade de tratamento para a SARS CoV-2, da mesma forma que é indicada para o tratamento da síndrome do desconforto respiratório neonatal.

Uso convencional de surfactante en recién nacidos con enfermedad de membrana hialina / Conventional use of surfactant in newborns with hyaline membrane disease

La enfermedad de membrana hialina se debe a la deficiencia de surfactante en los pulmones de los recién nacidos especialmente los menores de 37 semanas de gestación. El manejo materno con corticoides prenatales en este grupo, disminuye la morbimortalidad asociada a esta patología neonatal. Se analiza desde el punto de la evidencia actualmente existente la administración de surfactante a estos prematuros y se revisa el tipo de surfactante a administrar, cuando es el mejor momento para administrarlo, la dosis y la forma de administrarlo.

Hyaline membrane disease is due to surfactant deficiency in the lungs of newborns, especially those younger than 37 weeks gestation. Maternal management with prenatal corticosteroids in this group reduces the morbidity and mortality associated with this neonatal pathology. The administration of surfactant to these preterm infants is analyzed from the point of the currently existing evidence and the type of surfactant to be administered is reviewed, when is the best time to administer it, the dose and the form of administration.

Efficacy and safety of less invasive surfactant administration in the treatment of neonatal respiratory distress syndrome: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy and safety of less invasive surfactant administration (LISA) in the treatment of neonatal respiratory distress syndrome (NRDS).@*METHODS@#PubMed, Cochrane Library, Embase, China Biology Medicine disc, China Scientific Journal Database, CNKI Database, and Wanfang Database were searched for randomized controlled trials (RCTs) on the use of LISA strategy in the treatment of NRDS. Literature screening and quality assessment were performed according to inclusion and exclusion criteria. Review Manager 5.3 software was used to perform the Meta analysis.@*RESULTS@#A total of 9 RCTs were included, with a total of 1 212 children with NRDS. There were 611 children in the experimental group (treated with LISA strategy) and 601 children in the control group [treated with intubation-surfactant-extubation (INSURE) strategy]. The Meta analysis showed that the use of LISA strategy reduced the rate of mechanical ventilation within 72 hours after birth (OR=0.39, 95%CI: 0.29-0.51, P0.05). There was no significant difference in the rate of repeated use of pulmonary surfactant (PS) between the two groups (P>0.05), but there was a higher incidence rate of PS reflux observed by LISA strategy (OR=2.60, 95%CI: 1.64-4.12, P<0.001).@*CONCLUSIONS@#Compared with INSURE strategy, LISA strategy has advantages in reducing the need for mechanical ventilation and the incidence rates of bronchopulmonary dysplasia and pneumothorax in children with NRDS.

Dyspnea and ventilator dependence after birth in a full-term female infant / 中国当代儿科杂志

A female infant, aged 43 days, had shortness of breath, cyanosis, groan, and dyspnea since birth. Physical examination showed cyanosis of lips and three-concave sign, and multiple lung imaging examinations showed diffuse ground-glass opacities in both lungs. The girl was given anti-infective therapy and continuous mechanical ventilation but there were no significant improvements in symptoms. Gene testing confirmed a compound heterozygous mutation, c.1890C>A(p.Tyr630Ter)+c.3208G>A(p.Ala1070Thr), in the ABCA3 gene, with the former from her father and the latter from her mother. Pathological examination of the lungs indicated pulmonary interstitial disease. The girl was diagnosed with infantile diffuse pulmonary interstitial disease caused by mutations in the ABCA3 gene. When full-term neonates experience shortness of breath and dyspnea after birth, pulmonary imaging suggests diffuse ground-glass changes, and conventional treatment is not effective (ventilator-dependent), congenital pulmonary surfactant metabolism defects needs to be considered. Gene testing, which can provide a basis for early intervention, prognostic evaluation, and genetic counseling, should be performed as early as possible.

A single-center retrospective study of neonatal acute respiratory distress syndrome based on the Montreux definition / 中国当代儿科杂志

OBJECTIVE@#To investigate the epidemiology, clinical features, treatment, and prognostic factors of neonatal acute respiratory distress syndrome (NARDS) through a retrospective study of NARDS based on the Montreux definition.@*METHODS@#A retrospective analysis was performed on the medical records of neonates who were hospitalized from January 2017 and July 2018, among whom 314 neonates who met the Montreux definition were enrolled as subjects. According to oxygen index, they were divided into a mild NARDS group with 130 neonates, a moderate NARDS group with 117 neonates, and a severe NARDS group with 67 neonates. The clinical features were compared among the three groups to investigate the influencing factors for the severities of NARDS and the length of hospital stay.@*RESULTS@#The neonates with NARDS accounted for 2.46% (314/12 789) of the neonates admitted to the neonatal ward during the same period of time and had a mortality rate of 9.6% (30/314). The multivariate ordinal logistic regression analysis showed that the neonates who used pulmonary surfactant (PS) or had a long duration of assisted ventilation tended to have a higher risk of severe NARDS (@*CONCLUSIONS@#Preterm birth, low birth weight/macrosomia, and perinatal infection may be associated with an increased risk of severe NARDS. The neonates requiring invasive ventilation, prolonged assisted ventilation, or PS therapy tend to have a poor prognosis.

Dolor y variabilidad de la frecuencia cardíaca en recién nacidos prematuros que recibieron surfactante: un estudio piloto / Neonatal pain and heart rate variability in preterm infants treated with surfactant: a pilot study

Objetivo. Evaluar la percepción del dolor de recién nacidos prematuros a quienes se les administró surfactante mediante diferentes técnicas, utilizando la variabilidad de la frecuencia cardíaca (VFC).Métodos. Se aleatorizó a los recién nacidos que requirieron tratamiento con surfactante por SDR a los grupos INSURE o MIST. El análisis de la VFC se realizó con la tecnología NIPE para evaluar el componente parasimpático del sistema nervioso autónomo de los recién nacidos. Se registró la VFC antes, durante y después de administrar el surfactante. La evaluación del dolor se determinó con la escala PIPP. Resultados. Se incluyó a 14 recién nacidos en el estudio. Los grupos tenían características demográficas similares. Los puntajes de la escala PIPP no difirieron entre los grupos INSURE y MIST (p = 0,05). Se observó una diferencia estadísticamente significativa en la mediana de la VFC durante la administración del surfactante entre los grupos INSURE y MIST (52 frente a 56, p = 0,03). El análisis de la VFC fue similar entre los grupos antes y después de administrar el surfactante.Conclusión. La administración de surfactante mediante la técnica MIST podría ser más cómoda para los recién nacidos prematuros con SDR. No obstante, es necesario realizar otros estudios con series más importantes.

Objective. We aimed to assess the pain perception of preterm infants treated with different surfactant administration techniques by using heart rate variability (HRV).Methods. Preterm infants who required surfactant therapy for RDS were randomized to INSURE or MIST groups. HRV analysis was performed by Newborn Infant Parasympathetic Evaluation monitor. HRV was recorded before, during and after surfactant administration. Pain assessment was determined by Premature Infant Pain Profile (PIPP) score.Results. Fourteen infants were enrolled in the study. Demographic characteristics of the groups were similar. PIPP scores did not differ between INSURE and MIST groups (p = 0.05). Statistically significant difference in median HRV during surfactant administration was observed between INSURE and MIST groups (52 vs. 56, p = 0.03). HRV analysis was similar between groups before and after surfactant administration. Conclusion. Surfactant administration with MIST technique might be more comfortable for preterm infants with RDS. However further studies with larger series are needed.

Rapid diagnosis of respiratory distress syndrome by oral aspirate in premature newborns / Diagnóstico rápido da síndrome do desconforto respiratório por aspirado bucal em recém-nascidos prematuros

Abstract Objective: The stable microbubble test on gastric aspirate and on amniotic fluid has been used for the diagnosis of respiratory distress syndrome in the newborn. However, no study has performed this test on oral aspirates from premature infants. The objective of this study was to evaluate the performance of the stable microbubble test on oral aspirates from preterm newborns to predict respiratory distress syndrome. Method: This study included infants with gestational age <34 weeks. Oral fluids were obtained immediately after birth and gastric fluids were collected within the first 30 minutes of life. The samples were frozen and tested within 72 hours. Results: The sample was composed of paired aspirates from 64 newborns, who were divided into two groups: respiratory distress syndrome group (n = 21) and control group (n = 43). The median (interquartile range) of the stable microbubble count in the oral samples of infants with respiratory distress syndrome was significantly lower than that of infants who did not develop respiratory symptoms: respiratory distress syndrome group = 12 (8 -22) stable microbubbles/mm2; control group = 100 (48 -230) microbubbles/mm2 (p < 0.001). The correlation between microbubble count in gastric and oral aspirates was 0.90 (95% confidence interval = 0.85 -0.95; p < 0.001). Considering a cut-off point of 25 microbubbles/mm2, the sensitivity and the specificity of the stable microbubble test were 81.4% and 85.7%, respectively. Conclusion: The study suggests that the stable microbubble test performed on oral aspirate is a reliable alternative to that performed on gastric fluid for the prediction of respiratory distress syndrome in the newborn.

Resumo Objetivo: O teste das microbolhas estáveis no aspirado gástrico e no líquido amniótico foi usado no diagnóstico da síndrome do desconforto respiratório do recém-nascido. Contudo, nenhum estudo fez esse teste nos aspirados bucais de neonatos prematuros. O objetivo deste estudo foi avaliar o desempenho do teste das microbolhas estáveis em aspirados bucais de recém-nascidos prematuros para prever síndrome do desconforto respiratório. Método: Este estudo incluiu neonatos com idade gestacional < 34 semanas. Os fluidos orais foram obtidos imediatamente após o nascimento e os fluidos gástricos foram coletados nos primeiros 30 minutos de vida. As amostras foram congeladas e testadas em 72 horas. Resultados: A amostra foi composta de aspirados pareados de 64 recém-nascidos, divididos em dois grupos: grupo de síndrome do desconforto respiratório (n = 21) e grupo de controle (n = 43). A mediana (intervalo interquartil) da contagem das microbolhas estáveis nas amostras de fluido oral dos neonatos com síndrome do desconforto respiratório foi significativamente menor que a dos neonatos que não desenvolveram sintomas respiratórios: grupo de síndrome do desconforto respiratório = 12 (8-22) microbolhas estáveis/mm2; grupo de controle = 100 (48-230) microbolhas/mm2 (p < 0,001). A correlação entre a contagem das microbolhas nos aspirados gástricos e bucais foi 0,90 (intervalo de confiança de 95% = 0,85-0,95; p < 0,001). Considerando um ponto de corte de 25 microbolhas/mm2, a sensibilidade e a especificidade do teste das microbolhas estáveis foram 81,4% e 85,7%, respectivamente. Conclusão: O estudo sugere que o teste das microbolhas estáveis feito no aspirado bucal é uma opção confiável ao fluido gástrico para a predição da síndrome do desconforto respiratório do recém-nascido.

Seguridad del tratamiento con Surfacen® en recién nacidos pretérminos con síndrome de dificultad respiratoria / Safety of the treatment with Surfacen® in preterm newborns with syndrome of respiratory difficulty

Introducción: Varias han sido las publicaciones sobre Surfacen®, pero ninguna ha comparado la seguridad del producto entre su uso temprano y tardío. Objetivo: Comprobar las características de los eventos adversos en ambas formas de administración del producto. Métodos: Se realizó un estudio analítico observacional, no controlado, multicentro, nacional, desde 2007 al 2013. La muestra fue de 484 recién nacidos en los que se comprobaron los eventos adversos ocurridos por Surfacen® administrado de manera temprana y tardía. Las variables estudiadas fueron de caracterización general y de caracterización de los eventos adversos. Resultados: El grupo al que se le administró el surfactante de manera tardía tuvo mayor incidencia de eventos adversos que los tratados de manera temprana (277 vs 268). El porcentaje de pacientes con estos eventos fue mayor en los tratados de manera tardía (63,7 vs 41,3 por ciento). El rescate tardío tuvo 2,5 veces más riesgo de presentar la hemorragia peri- e intraventricular (10,4 vs 4,0 por ciento), mayor riesgo de presentar las diferentes formas de bloqueo aéreo, tres veces más riesgo de displasia broncopulmonar (8,8 vs 2,6 por ciento) y 6 veces más riesgo de presentar desaturación de oxígeno, que el rescate temprano. Conclusiones: El tratamiento con Surfacen®, tanto en su forma de rescate temprano como tardío presenta los mismos eventos adversos que otros surfactantes utilizados y el tratamiento de rescate temprano tiene menos riesgo de presentar eventos adversos como son la hemorragia intraventricular, el bloqueo aéreo, displasia broncopulmonar y desaturación de oxígeno, por lo que su administración es segura(AU)

Introduction: There have been several publications on SURFACEN®, but none has compared the safety of this product in the early and late uses of it. Objective: To check the characteristics of adverse events in both ways of administering the product. Methods: It was carried out an analytic, observational, non- controlled, national multicentric study from 2007 to 2013. The sample consisted of 484 newborns in whom were checked the adverse events occurred in the early and late ways by administered SURFACEN®. The studied variables were of general characterization and of characterization of the adverse events. Results: The group to which the surfactant was administered in a late way had more incidences of adverse events than the ones treated earlier (277 vs 268). The percentage of patients with these events was higher in the ones treated in a late way (63.7 vs 41.3 percent). The late rescue had 2.5 times more risk of presenting peri- and intra-ventricular hemorrhage (10.4 vs 4.0 percent), higher risk of presenting the different forms of air block, three times more risk of bronchopulmonary dysplasia (8.8 vs 2.6 percent), and six times more risk of presenting oxygen desaturation. Conclusions: As much in the way of early rescue as in the late one, the treatment with SURFACEN® presents the same adverse events that other used surfactants; and the early rescue's treatment has less risk of presenting adverse events or intraventricular hemorrhage, air block, bronchopulmonary dysplasia and oxygen desaturation, that is why its administration is safe(AU)

El intersticio pulmonar y sus enfermedades en la infancia. Confusión diagnóstica en el recién nacido. Enfermedades genéticas del surfactante pulmonar. A propósito de un caso clínico: clínica, radiología, estudios y diagnóstico diferencial / The pulmonary interstitium and its diseases in childhood. Diagnostic confusion in the new born. Genetic diseases of pulmonary surfactant. About a clinical case: clinical, radiology, studies and differential diagnosis

Se presenta el caso clínico de un lactante fallecido a los siete meses de edad con cuadro intersticial persistente. Objetivos: describir detalladamente el camino diagnóstico; alertar sobre posibles confusiones en recién nacidos con diagnósticos más frecuentes; detallar los hallazgos clínicos, radiológicos y de anatomía patológica (consultas en el exterior). Metodología: sumatoria de estudios complejos para descartar causas más frecuentes de patología intersticial en el lactante; consultas radiológicas, de anatomía patológica y genética en el exterior del país. Resultado: con diagnóstico de PAP (proteinosis alveolar pulmonar) se encontró una duplicación de material genético a nivel de cromosoma X, correspondiente al gen CSF2RA (colony stimulating factor 2-subunidad a). Este gen codifica al receptor CSF2 cuya citoquina controla la producción, diferenciación y función de granulocitos/macrófagos. (AU)

A clinical case of a deceased seven month old infant presenting persistent interstitial lung compromise is presented. Objectives. Detailed description of the diagnostic pathway used; to alert about possible confusion with other ­ more frequent ­ pathologies in the new borninfant age; to present clinical, radiological, genetic and pathology findings (consultations abroad). Methodology. A complete description of complex studies to rule out other more frequent pathologies is presented together with radiological, pathological and genetic results from consultations abroad. Results. A diagnosis of PAP (pulmonary alveolar proteinosis) was confirmed with duplication of genetic material at CSF2RA gene (colony stimulating factor 2-subunit a). This gene codifies the CSF2 receptor whose cytokine controls production, differentiation and function of granulocytes/macrophages. (AU)

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.

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.

Clinical effect of exogenous pulmonary surfactant in the treatment of severe neonatal infectious pneumonia: a multicenter prospective clinical trial / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect of calsurf, a domestic exogenous pulmonary surfactant, in the treatment of severe neonatal infectious pneumonia.@*METHODS@#A total of 208 neonates with severe infectious pneumonia who hospitalized in 5 hospitals of China were enrolled. According to their parents' wishes on admission, these neonates were administered with conventional treatment (control group; n=81) and calsurf  treatment + conventional treatment (calsurf treatment group, n=127). The two groups were compared in terms of the degree of oxygen dependence on admission, blood gas parameters before and after treatment, lung ultrasound results, duration of mechanical ventilation, length of hospital stay, hospital costs, complications and prognosis.@*RESULTS@#Compared with the control group on admission, the calsurf treatment group had significantly higher inhaled oxygen concentration and partial pressure of carbon dioxide and significantly lower arterial partial pressure of oxygen and oxygenation index (P<0.01). After 1 hour of treatment, both groups had significant improvements in the above indices (P<0.05), and the improvements were more significant in the calsurf treatment group (P<0.05). After 4-6 hours of calsurf administration, there was a significant reduction in the degree of pulmonary consolidation. The calsurf treatment group had significantly shorter duration of mechanical ventilation and length of hospital stay than the control group, while there was no significant difference in the incidence rate of complications between the two groups. The neonates of both groups had a good prognosis.@*CONCLUSIONS@#In neonates with severe infectious pneumonia, calsurf treatment can significantly improve oxygenation, reduce the degree of pulmonary consolidation, and shorten the duration of mechanical ventilation and length of hospital stay. Therefore, it should be considered in neonates with severe infectious pneumonia.

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.

Clinical features and prognosis of meconium aspiration syndrome complicated by pulmonary hemorrhage in neonates / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and prognosis of meconium aspiration syndrome (MAS) complicated by neonatal pulmonary hemorrhage (NPH) in neonates.@*METHODS@#A retrospective analysis was performed for the clinical data of 45 neonates with MAS complicated by NPH who were admitted to the hospital from December 2015 to December 2018 (observation group). Ninety neonates with MAS who were hospitalized during the same period of time and had no pulmonary hemorrhage were enrolled as the control group. The two groups were compared in terms of clinical features and prognosis.@*RESULTS@#The observation group had a significantly lower 1-minute Apgar score after birth than the control group (P<0.05). Compared with the control group, the observation group had significantly higher incidence rates of persistent pulmonary hypertension of the newborn, air leak syndrome and shock and a higher rate of use of pulmonary surfactant (P<0.05), as well as higher levels of C-reactive protein and oxygen index (OI) (P<0.01). In the early diagnosis of NPH, OI had a sensitivity of 80.0%, a specificity of 96.7%, and an area under the receiver operating characteristic curve of 0.959 (95% confidence interval: 0.929-0.988, P<0.001) at the cut-off value of 10.05. For the children who were cured and discharged, the observation group had significantly longer duration of ventilation, duration of oxygen inhalation and length of hospital stay than the control group (P<0.05).@*CONCLUSIONS@#Neonates with MAS complicated by NPH tend to have a longer duration of ventilation and higher incidence rates of air leak syndrome and shock. OI may be used as an index for the early diagnosis of MAS complicated by NPH.

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.