The mouse multi-organ proteome from infancy to adulthood.

The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.

Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease, associated with premature birth, that arises during the infantile period. It is an evolving disease process with an unchanged incidence due to advancements in neonatal care which allow for the survival of premature infants of lower gestational ages and birth weights. Currently, there are few effective interventions to prevent BPD. However, careful attention to BPD phenotypes and comprehensive care provided by an interdisciplinary team have improved care. Interventions early in the disease course hold promise for improving long-term survival and outcomes in adulthood for this high-risk population.

Biophysics of morphogenesis in the vertebrate lung.

Morphogenesis is a physical process that sculpts the final functional forms of tissues and organs. Remarkably, the lungs of terrestrial vertebrates vary dramatically in form across species, despite providing the same function of transporting oxygen and carbon dioxide. These divergent forms arise from distinct physical processes through which the epithelium of the embryonic lung responds to the mechanical properties of its surrounding mesenchymal microenvironment. Here we compare the physical processes that guide folding of the lung epithelium in mammals, birds, and reptiles, and suggest a conceptual framework that reconciles how conserved molecular signaling generates divergent mechanical forces across these species.

Factors Associated With Radiological Lung Growth Rate After Lobectomy in Patients With Lung Cancer.

INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.

Bulk RNA sequencing of human pediatric lung cell populations reveals unique transcriptomic signature associated with postnatal pulmonary development.

Postnatal lung development results in an increasingly functional organ prepared for gas exchange and pathogenic challenges. It is achieved through cellular differentiation and migration. Changes in the tissue architecture during this development process are well-documented and increasing cellular diversity associated with it are reported in recent years. Despite recent progress, transcriptomic and molecular pathways associated with human postnatal lung development are yet to be fully understood. In this study, we investigated gene expression patterns associated with healthy pediatric lung development in four major enriched cell populations (epithelial, endothelial, and nonendothelial mesenchymal cells, along with lung leukocytes) from 1-day-old to 8-yr-old organ donors with no known lung disease. For analysis, we considered the donors in four age groups [less than 30 days old neonates, 30 days to < 1 yr old infants, toddlers (1 to < 2 yr), and children 2 yr and older] and assessed differentially expressed genes (DEG). We found increasing age-associated transcriptional changes in all four major cell types in pediatric lung. Transition from neonate to infant stage showed highest number of DEG compared with the number of DEG found during infant to toddler- or toddler to older children-transitions. Profiles of differential gene expression and further pathway enrichment analyses indicate functional epithelial cell maturation and increased capability of antigen presentation and chemokine-mediated communication. Our study provides a comprehensive reference of gene expression patterns during healthy pediatric lung development that will be useful in identifying and understanding aberrant gene expression patterns associated with early life respiratory diseases.NEW & NOTEWORTHY This study presents postnatal transcriptomic changes in major cell populations in human lung, namely endothelial, epithelial, mesenchymal cells, and leukocytes. Although human postnatal lung development continues through early adulthood, our results demonstrate that greatest transcriptional changes occur in first few months of life during neonate to infant transition. These early transcriptional changes in lung parenchyma are particularly notable for functional maturation and activation of alveolar type II cell genes.

Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.

OBJECTIVE: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort. METHODS: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories. RESULTS: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth. CONCLUSION: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

Developmental changes in lung function of mice are independent of sex as a biological variable.

Pulmonary function testing (PFT) in mice includes biomechanical assessment of lung function relevant to physiology in health and its alteration in disease, hence, it is frequently used in preclinical modeling of human lung pathologies. Despite numerous reports of PFT in mice of various ages, there is a lack of reference data for developing mice collected using consistent methods. Therefore, we profiled PFTs in male and female C57BL/6J mice from 2 to 23 wk of age, providing reference values for age- and sex-dependent changes in mouse lung biomechanics during development and young adulthood. Although males and females have similar weights at birth, females weigh significantly less than males after 5 wk of age (P < 0.001) with largest weight gain observed between 3 and 8 wk in females and 3 and 13 wk in males, after which weight continued to increase more slowly up to 23 wk of age. Lung function parameters including static compliance and inspiratory capacity also increased rapidly between 3 and 8 wk in female and male mice, with male mice having significantly greater static compliance and inspiratory capacity than female mice (P < 0.001). Although these parameters appear higher in males at a given age, allometric scaling showed that static compliance and inspiratory compliance were comparable between the two sexes. This suggests that differences in measurements of lung function are likely body weight-based rather than sex-based. We expect these data to facilitate future lung disease research by filling a critical knowledge gap in our field.NEW & NOTEWORTHY This study provides reference values for changes in mouse lung biomechanics from 2 to 23 wk of age. There are rapid developmental changes in lung structure and function of male and female mice between the ages of 3 and 8 wk. Male mice become noticeably heavier than female mice at or about 5 wk of age. We identified that differences in normal lung function measurements are likely weight-based, not sex-based.

Distribution of calcitonin gene-related peptide and vascular endothelial growth factor in the mouse lung at the embryonic and postnatal stages / Distribución del péptido relacionado con el gen de la calcitonina y el factor de crecimiento endotelial vascular en el pulmón de ratón en las etapas embrionaria y posnatal

SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.

El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.

Development of Lung Function in Preterm Infants During the First Two Years of Life / Desarrollo de la función pulmonar en lactantes pretérmino durante los 2 primeros años de vida

Introduction: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function. (AU)

Introducción: Todavía no está claro si la prematuridad por sí sola puede tener influencia en el desarrollo pulmonar tras el parto y, en particular, en el tamaño bronquial.ObjetivoValorar la función pulmonar durante los 2 primeros años de vida en lactantes pretérmino sanos y comparar las medidas con las obtenidas en lactantes nacidos a término sanos durante el mismo periodo de tiempo.MétodosEste ensayo longitudinal observacional valoró la función pulmonar en 74 lactantes pretérmino (30+0 a 35+6 semanas de edad gestacional) y 76 lactantes nacidos a término sanos como controles, que se seleccionaron entre 2011 y 2013. Se llevaron a cabo las mediciones de la respiración corriente, la mecánica respiratoria pasiva, los flujos espiratorios forzados a volumen corriente y con insuflación previa (V’maxFRC y FEF25-75, respectivamente) tras la sedación con hidrato de cloral siguiendo las recomendaciones de las ATS/ERS a la edad corregida de 6 y 18 meses.ResultadosInicialmente se obtuvieron las medidas de función pulmonar de los lactantes pretérmino y los controles a término a los 6 meses de edad. Los lactantes pretérmino presentaron unos valores absolutos y ajustados (a la edad gestacional, la edad posnatal, el sexo, el tamaño corporal y los factores de confusión) menores para la distensibilidad pulmonar y la V’maxFRC. A los 18 meses de edad posnatal corregida, se repitieron las mismas mediciones en 57 lactantes pretérmino y 61 controles a término. Se observó una recuperación del volumen corriente, los parámetros de mecánica respiratoria, el FEV0,5 y los flujos espiratorios forzados en los lactantes pretérmino.ConclusiónEn comparación con los controles a término, los flujos espiratorios forzados más bajos observados en el grupo de pretérminos sanos a los 6 meses no se observaron a los 18 meses de edad corregida, lo que evidencia un crecimiento de recuperación de la función de la vía respiratoria. (AU)

Long non-coding RNA NANCI/NKX2-1 duplex impacts prognosis in stage I non-small-cell lung cancer / La combinación de NANCI/NKX2-1 de ARN no codificante de cadena larga afecta al pronóstico del cáncer de pulmón de células no pequeñas en estadio I

BACKGROUND: NANCI, an intergenic long non-coding RNA (lncRNA) is essential for buffering NKX2-1 expression during embryonic development and in adult tissue. We analyzed NANCI and NKX2-1 in human lung embryonic samples and adult lung tissues and evaluated their potential as prognostic markers in stage I non-small cell lung cancer (NSCLC). METHODS AND RESULTS: NANCI and NKX2-1 expression was assessed by TaqMan assays in 18 human embryonic samples from 8 to 13 weeks, 59 non-tumoral (NT) lung tissue samples, and 98 stage I NSCLC tumor samples. NANCI and NKX2-1 expression in embryonic and NSCLC samples were downregulated in comparison to adult NT tissue. Patients with low expression of NANCI had shorter disease-free survival (DFS) and overall survival (OS) than those with high levels (47.6 vs 69.3 months, P = 0.032 and 57.7 vs 77.6 months, P = 0.021, respectively). When the expression levels of NANCI and NKX2-1 were evaluated in combination, four groups were identified (high NANCI/high NKX2-1, low NANCI/high NKX2-1, high NANCI/low NKX2-1 and low NANCI/low NKX2-1) with differential impact on DFS (P = 0.042) and OS (P = 0.024). Interestingly, the high NANCI/high NKX2-1 duplex group had longer DFS and OS than the other three groups (71.25 vs 46.3 months, P = 0.009 and 81.3 vs 56.1 months, P = 0.004, respectively). In the multivariate analysis, the high NANCI/high NKX2-1 duplex was identified as an independent prognostic factor for longer DFS (HR 0.346, 95% CI, 0.169-0.709; P = 0.004) and OS (HR 0.309, 95% CI, 0.121-0.786; P = 0.014). CONCLUSIONS: NANCI and the NANCI-NKX2-1 duplex impacts prognosis in stage I NSCLC patients

CONTEXTO GLOBAL: NANCI, un ARN intergénico largo no codificante (lncRNA) es esencial para regular la expresión de NKX2-1 durante el desarrollo embrionario y en el tejido adulto. Analizamos la expresión de NANCI y NKX2-1 en muestras embrionarias de pulmón humano y tejidos pulmonares adultos, y evaluamos su potencial como marcadores pronósticos en el cáncer de pulmón de células no pequeñas (CPCNP) en estadio I. MÉTODOS Y RESULTADOS: La expresión de NANCI y NKX2-1 se evaluó mediante ensayos TaqMan® en 18 muestras embrionarias humanas de 8 a 13 semanas, 59 muestras de tejido pulmonar no tumoral (NT) y 98 muestras de tumor de CPCNP en estadio i. La expresión de NANCI y NKX2-1 en muestras embrionarias y NSCLC se encontraba reducida en comparación con el tejido NT adulto. Los pacientes con baja expresión de NANCI tuvieron una supervivencia libre de enfermedad (SLE) y una supervivencia general (SG) más cortas que aquellos con niveles altos (47,6 frente a 69,3 meses; p = 0,032 y 57,7 frente a 77,6 meses; p = 0,021, respectivamente). Cuando se evaluaron los niveles de expresión de NANCI y NKX2-1 combinados se identificaron 4 grupos (NANCI alto/NKX2-1 alto, NANCI bajo/NKX2-1 alto, NANCI alto/NKX2-1 bajo y NANCI bajo/NKX2-1 bajo) con impacto variable en la SLE (p = 0,042) y la SG (p = 0,024). Curiosamente, la combinación de NANCI alto/NKX2-1 alto presentó unas SLE y SG más largas que los otros 3 grupos (71,25 frente a 46,3 meses; p = 0,009 y 81,3 frente a 56,1 meses; p = 0,004, respectivamente). En el análisis multivariante, la combinación de NANCI alto/NKX2-1 alto se identificó como un factor de pronóstico independiente para una SLE más larga (HR: 0,346; IC 95%: 0,169-0,709; p = 0,004), al igual que la SG (HR: 0,309; IC 95%: 0,121-0,786; p = 0,014). CONCLUSIONES: NANCI y la combinación de NANCI-NKX2-1 afecta al pronóstico de los pacientes con CPCNP en estadio i

Avaliação da maturidade pulmonar de cabritos nascidos a termo e prematuros / [Evaluation of lung maturity of term and premature kid]

Avaliou-se a maturidade pulmonar de cabritos no líquido amniótico de suas mães pela coloração de Shor, pelo azul de Nilo e pela contagem de corpos lamelares, bem como a vitalidade e os níveis de glicose e lactato séricos em cabritos nascidos a termo e prematuros. Para tanto, foram utilizados 32 cabritos, divididos em três grupos, a saber: grupo I: cabritos nascidos de cesarianas com 149 dias de gestação; grupo II: cabritos nascidos de cesarianas com 143 dias de gestação; e grupo III: cabritos nascidos de cesarianas com 143 dias de gestação, oriundos de mães que receberam, por via intramuscular, 20mg/cabra de dexametasona, 36 horas antes da cirurgia eletiva. A coloração de Shorr e a contagem de corpos lamelares demonstraram ser métodos diagnósticos promissores para a avaliação da maturidade pulmonar em neonatos caprinos. Contudo, a administração de dexametasona nas cabras no período antenatal não influenciou a maturidade fetal. Constatou-se, entretanto, que a avaliação física do paciente, logo após o nascimento, também se mostra fundamental no que tange à percepção da vitalidade e da viabilidade de cabritos recém-nascidos.(AU)

Pulmonary maturity of goats in their amniotic fluid was evaluated by Shor, Nile blue staining, and lamellar body count, as well as vitality and serum glucose and lactate levels in term and premature goats. Twenty-four kids were divided into three groups: group I: comprised of eight animals born by cesarean section with 149 days of gestation; group II: comprised of eight animals born by cesarean section with 143 days of gestation; and group III: comprised of eight animals born by cesarean section with 143 days of gestation, in which the does received intramuscular dexamethasone (20mg/goat) 36 hours prior to elective cesarean section. Shorr staining and lamellar body count have shown to be promising diagnostic methods for the assessment of lung maturity in goat neonates. However, the administration of dexamethasone to goats during antenatal period did not influence fetal maturity. It was verified that the physical evaluation of the patient, shortly after birth, is fundamental for the perception of vitality and viability of newborn goats.(AU)

Short-term perinatal oxygen exposure may impair lung development in adult mice

BACKGROUND: Hyperoxia at resuscitation increases oxidative stress, and even brief exposure to high oxygen concentrations during stabilization may trigger organ injury with adverse long-term outcomes in premature infants. We studied the long-term effects of short-term perinatal oxygen exposure on cell cycle gene expression and lung growth in adult mice. METHODS: We randomized mice litters at birth to 21,40, or 100%O2 for 30 min and recovered in room air for 4 or 12 weeks. Cell cycle gene expression, protein analysis, and lung morphometry were assessed at 4 and 12 weeks. RESULTS: The principal component analysis demonstrated a high degree of correlation for cell cycle gene expression among the three oxygen groups. Lung elastin was significantly lower in the 100%O2 groups at 4 weeks. On lung morphometry, radial alveolar count, alveolar number, and septal count were similar. However, the mean linear intercept (MLI) and septal length significantly correlated among the oxygen groups. The MLI was markedly higher in the 100%O2 groups at 4 and 12 weeks of age, and the septal length was significantly lower in the 100%O2 groups at 12 weeks. CONCLUSION: Short-term exposure to high oxygen concentrations lead to subtle changes in lung development that may affect alveolarization. The changes are related explicitly to secondary crest formation that may result in alteration in lung elastin. Resuscitation with high oxygen concentrations may have a significant impact on lung development and long-term outcomes such as BPD in premature infants.

Evaluation of pulmonary maturity in bovine neonates: analysis of amniotic fluid / Avaliação maturidade pulmonar em neonatos bovinos: análise do líquido amniótico

Considering the representativeness of dairy cattle in our country, the concern about the mortality rates of the animals increases each time. Regarding to calf mortality, the Respiratory Distress Syndrome (RDS) has an important relevance during the neonatal period, and it is present in immature lungs. The amniotic fluid is in direct contact with the fetus, and it is able to offer evidence about his maturity. The aim of this study was to standardize the characteristics of the amniotic fluid, color, aspect, viscosity, quantification of lamellar body and surfactant evaluation by the Clements test and cytology, of term-born, mature and healthy calves. There were used 50 Black and White Holstein calves, which mothers were observed at calving in order to collect the amniotic fluid by puncture in the moment of exposure of the fetal membrane through the vaginal canal. Most amniotic fluid had a clear and hazy appearance due to varying degrees of viscosity and the presence or absence of clots. The Clements test could be adapted to the bovine species by the modification consisting in the addition of 3mL of amniotic fluid and 1mL of 95% ethanol. The methodology of the lamellar body count by the automated particle counter is not applicable for the bovine because of the small size of their lamellar body. The Nile Blue staining is unsatisfactory on predicting fetal maturity on the bovine species, different from cytology using Hematoxylin-Shorr stain. The presence of orange cells, increase in large amounts at the end of pregnancy. The cell stained orange counting, cells which are found in great amounts at the end of pregnancy. The present study stablished new parameters for evaluation of fetal and pulmonary maturity in the bovine species.(AU)

O objetivo desse estudo foi reunir novos dados práticos sobre a avaliação da maturidade pulmonar em neonatos bovinos, padronizando as características do líquido amniótico de bezerros maduros e hígidos, o que proporcionará a oportunidade de tratamento precoce dos animais prematuros, evitando prejuízos econômicos, principalmente quando consideramos os animais de alto valor genético. Amostras de líquido amniótico foram coletadas de 50 vacas da Raça Holandesa Preta e Branca. Corpos lamelares foram identificados por microscopia eletrônica de transmissão como estruturas de tamanho aproximado de 130nm, o que impede sua contagem em analisadores automáticos. O teste de Clements sofreu adaptações de técnica e se mostrou viável com a diluição de 3mL de líquido amniótico em 1mL de etanol a 95%. A citologia utilizando o método de Hematoxilina-Shorr, diferentemente do teste de Azul de Nilo, foi eficaz na identificação das células orangiofílicas, indicativas de maturidade fetal. Esses métodos mostraram-se originais e úteis ferramentas para a avaliação de maturidade pulmonar na espécie bovina, porém estudos com bezerros prematuros ainda são necessários.(AU)

Maduración pulmonar fetal: efectos sobre la morbilidad respiratoria en prematuros tardíos / Fetal pulmonary maturation: effects on respiratory morbidity in late preterm infants

INTRODUCCIÓN: Los recién nacidos entre las 34 y las 36 semanas de gestación (SEG), definidos actualmente como "prematuros tardíos" (RNPTT) requieren en mayor frecuencia de internación en unidades de cuidados intensivos neonatales, siendo la morbilidad respiratoria una de las principales causas de internación. El uso de corticoides prenatales ha demostrado mejorar la función pulmonar en prematuros extremos (<27,6 SEG), muy prematuros (28-31,6 SEG) y prematuros moderados, (32-36,6 SEG) pero no han sido evaluados en forma extensa en el período prematuro tardío y no existen datos concluyentes al respecto. OBJETIVO: Comparar la frecuencia en que se presenta la morbilidad respiratoria en RNPTT con o sin maduración pulmonar previa. Establecer los factores asociados a morbilidad respiratoria en RNPTT. Comparar los pacientes RNPTT con y sin maduración pulmonar: los requerimientos de internación en general, requerimiento de internación por morbilidad respiratoria y en estos, días de oxigenoterapia y necesidad de ARM y/o VNI. MÉTODO: Diseño observacional, retrospectivo y analítico. Población constituida por todos los RNPTT que nacieron en la CURF entre el 1 de enero de 2017 y el 31 de diciembre de 2017. Las variables maternas y neonatales se compararán entre los dos grupos RNPTT con o sin maduración pulmonar. La frecuencia de presentación de la morbilidad respiratoria entre los RNPTT con o sin maduración pulmonar, los factores asociados a morbilidad respiratoria, los requerimientos de internación y necesidad de ARM y VNI se compararon con la prueba de chicuadrado siendo estadísticamente significativa la diferencia entre los mismos con P ≤0,05. Los días de internación se compararon mediante la prueba de T de Student. El Software que se utilizó para procesar los datos estadísticos será el SPSS versión 11.0 (Chicago, IL). RESULTADOS: De los RNPTT estudiados (160) N=86 (53.7 %) recibieron corticoides prenatales completos. La edad gestacional media (DE) de administración fueron 35,2 (2,2) semanas. La frecuencia de morbilidad respiratoria fue de 21,2%. No hubo diferencia en la frecuencia de morbilidad respiratoria global entre ambos grupos (p 0,3777). El sexo masculino (51,3% vs 49.0%; p= 0,0034) la APP (34,09%; p= 0,0197) y morbilidad materna (preeclampsia, app, diabetes gestacional, corioamnionitis, RPM, placenta previa, HIE) (70,65%; p= 0,0062) se asociaron a morbilidad respiratoria. No hubo diferencias en el requerimiento de internación ni en el número de días de internación entre ambos grupos. Tampoco se observó diferencias en el requerimiento de oxígeno, ARM, VNI, uso de surfactante y necesidad de reanimación. Tampoco se hallaron diferencias en la frecuencia de enfermedad de membrana hialina, taquipnea transitoria del recién nacido, neumotórax. Hubo tendencia a una disminución de la frecuencia de SDRA (6,35 % vs 33.33%, p= 0,051) en el grupo que recibió maduración pulmonar como así también una mayor frecuencia de apneas 25% (p= 0,0392). CONCLUSIÓN: En este estudio la maduración pulmonar con corticoides no influencio la frecuencia de morbilidad respiratoria global. Sin embargo, al analizar las patologías respiratorias de manera individual, encontramos una tendencia a la disminución de SDRA en el grupo madurado. La frecuencia de apneas fue mayor en el grupo que recibió corticoides lo que requiere un análisis con mayor profundidad. El sexo masculino como así también la APP y morbilidad materna se asociaron a mayor frecuencia de morbilidad respiratoria. (AU)

INTRODUCTION: Newborns between 34 and 36 weeks of gestation (WG), currently defined as "latepreterm infants" (LPTI), require of admission in neonatal intensive care units more frequently, with respiratory morbidity being one of the main causes of hospitalization. The use of prenatal corticosteroids has been shown to improve lung function in extremely preterm (<27.6 WG), very preterm (28-31.6 WG), and moderate preterm infants (32-36.6 WG), but it has not been evaluated extensively in the late-preterm period, leaving no conclusive data in this regard. OBJECTIVES: To compare the frequency of respiratory morbidity in LPTI with and without previous lung maturation. To establish the factors associated with respiratory morbidity in LPTI. • To compare LPTI patients with and without lung maturation: the requirements for hospitalization in general, the need for hospitalization due to respiratory morbidity, and in these cases, days of oxygen therapy and need for MRA and / or NIV. METHOD: Observational, retrospective and analytical design. Population constituted by all LPTI that were born in the CURF between January 1, 2017 and December 31, 2017. Maternal and neonatal variables were compared between LPTI groups with and without lung maturation. The frequency of presentation of respiratory morbidity among LPTI with or without lung maturation, the factors associated with respiratory morbidity, the requirements for hospitalization and the need for MRA and NIV were compared with the chi-square test, considering statistically significant the difference between them with P ≤0.05. Days of hospitalization were compared using the Student's T test. The software used to process the statistical data was the SPSS version 11.0 (Chicago, IL). RESULTS: Of the LPTI studied (160), N = 86 (53.7%) received complete antenatal corticosteroids. Mean gestational age (SD) for administration was 35.2 (2.2) weeks. The frequency of respiratory morbidity was 21.2%. There was no difference in the frequency of overall respiratory morbidity between both groups (p 0.3777). Male sex (51,3% vs 49.0%; p= 0,0034), preterm birth risk (34,09%; p= 0,0197) and maternal morbidity (preeclampsia, preterm birth risk, gestational diabetes, chorioamnionitis, preterm membrane rupture, previous placenta, pregnancy-induced hypertension) (70,65%; p= 0,0062) were associated to respiratory morbidity. There were no differences regarding hospitalization requirement or the number of hospitalization days between both groups. No differences were observed in oxygen requirement, MRA, NIV, use of surfactant and need for resuscitation. No differences were found in the frequency of hyaline membrane disease, newborn transient tachypnea and pneumothorax. There was a tendency to a decrease in the frequency of RDS (6.25% vs 33.33%; p= 0.051), and a higher frequency of apneas (25.0% vs 0%; p= 0.0392) in the group of patients who received lung maturation. CONCLUSION: In this study, pulmonary maturation with corticosteroids did not influence the frequency of global respiratory morbidity. However, when analyzing respiratory pathologies individually, we found a tendency to decrease of RDS in the matured group. The frequency of apneas was higher in the group that received corticosteroids, which requires further analysis. Male sex as well as preterm birth risk and maternal morbidity were associated to a higher frequency of respiratory morbidity

Vascular and ventilatory mechanical responses in three different stages of pulmonary development in the rabbit model of congenital diaphragmatic hernia

Abstract Purpose: To evaluate the vascular ventilatory response in different stages of lung development and to compare them to the neonates with congenital diaphragmatic hernia (CDH) in a rabbit model. Methods: New Zealand rabbits were divided into 8 groups (n=5): E25, E27, E30, and CDH. All groups were ventilated on a FlexiVent (Scireq, Montreal, QC, Canada), compounding the other 4 groups. The CDH surgery was performed at E25 and the harvest at E30. Dynamic compliance (CRS), dynamic elastance (ERS) and dynamic resistance (RRS) were measured every 4 min/24 min. Median wall thickness (MWT) and airspace were measured. ANOVA Bonferroni tests were used to perform statistical analysis. Significance was considered when p<0.05. Results: CRS was higher in E30 compared to all other groups (p<0.05). CRS and RRS of CDH and E27 were similar and were higher in E25 (p<0.05). MWT was decreased according to the gestational age, was increased in E27V and E30V (p<0.05) and decreased in CDHV (p<0.05), airspace was decreased in E25 and increased in all ventilated groups (p<0.05). Conclusions: The ventilation response of congenital diaphragmatic hernia is like the pseudoglandular stage of the lung development. These findings add information about the physiology of pulmonary ventilation in CDH.

Impacto da corticoterapia no prognóstico do prematuro tardio / Impact of corticoisteroids on late preterm prognosis: systematic review

Pouco se sabe sobre os efeitos da corticoterapia antenatal (CTA) nos fetos pré-termo tardios (PTT). Esta revisão tem como proposta examinar se há, ou não, benefícios no uso de corticoide para o incremento da maturação pulmonar fetal e melhoria dos resultados perinatais. Vários estudos avaliando as desordens respiratórias no neonato, a redução da morbimortalidade neonatal e duração do tempo de internação deram suporte a esta revisão. Parece não haver melhora da morbidade respiratória e suas complicações com a utilização da corticoterapia nos PTT, concluindo-se pela necessidade de mais estudos, em especial direcionados para casos de gestações que não apresentem maturidade pulmonar após 34 semanas com maior risco de parto prematuro.(AU)

Little is known about the effects of antenatal corticosteroids in late pre-term fetuses. This review clarify whether there is benefits in using steroids in late pre-term fetus to increase fetal lung maturation and improve perinatal outcomes, or not. Several studies in which the primary outcomes were respiratory disorders, neonatal mortality and hospitalization length were examined in this review. It seems that corticosteroids do not improve respiratory morbidity or its complications. It is concluded that more studies, in particular those including pregnancies with fetal lung immaturity after 34 weeks presenting higher risk of premature labor.(AU)

Malformación adenomatoide quística pulmonar. Diagnóstico prenatal / Cystic adenomatoid malformations of the lung. Prenatal diagnosis

La malformación adenoidea quística (MAQ) es una infrecuente alteración del desarrollo pulmonar, que puede ser diagnosticada por ecografía a lo largo de la gestación. Se presenta el caso de una MAQ aislada que se resolvió de manera espontánea intraútero

Cystic adenomatoid malformations (CAM) are relatively rare developmental abnormalities of the lung, which can be diagnosed by ultrasound during pregnancy. We report a case of CAM with no other associated abnormalities that resolved naturally in-utero

Cuantificación de la señal T2 pulmonar por resonancia magnética como factor pronóstico en las hernias diafragmáticas congénitas fetales / Prognostic usefulness of derived T2-weighted fetal magnetic resonance imaging measurements in congenital diaphragmatic hernia

Objetivo: Determinar el pronóstico neonatal de la hernia diafragmática congénita (HDC) partiendo de la señal relativa del pulmón contralateral en secuencias rápidas T2 de resonancia magnética (RM) fetal. Material y métodos: Estudiamos mediante ecografía y RM 28 fetos afectos de HDC y valoramos retrospectivamente en la ecografía fetal la relación entre el cociente observado y el esperado del diámetro axial máximo del pulmón dividido por el perímetro craneal (O/E LHR) y la posición hepática, y en la RM fetal el cociente de señal pulmón/hígado (LLSR) y el cociente de señal pulmón/líquido cefalorraquídeo (L/SF SR). Para determinar su valor pronóstico, los comparamos con los parámetros posnatales: supervivencia, hipertensión pulmonar, necesidad de oxígeno y la necesidad de oxigenación con membrana extracorpórea. Resultados: Encontramos diferencias significativas entre O/E LHR y la necesidad de oxigenación con membrana extracorpórea posnatal (p = 0,033) y la supervivencia posnatal (p = 0,01), y entre el LLSR de los fetos que sobrevivieron más de 45 días y los que no, con unas medianas de 1,91 y 2,56 respectivamente (p = 0,039). Conclusiones: El LLSR se correlaciona con la supervivencia posnatal en fetos con HDC y puede potencialmente utilizarse como parámetro pronóstico de la HDC fetal (AU)

Objective: To determine the usefulness of various parameters based on T2-weighted fetal magnetic resonance (MR) imaging measurements of the uninvolved lung for the neonatal prognosis of congenital diaphragmatic hernia (CDH). Material and methods: We used ultrasonography and MR imaging to study 28 fetuses with CDH. We retrospectively analyzed a) on fetal ultrasonography, the observed-to-expected lung to head ratio (O/E LHR) and the position of the liver, and b) on fetal MR imaging, the lung-liver signal ratio (LLSR) and the lungcerebrospinal fluid ratio (L/CSF SR). To determine the prognostic value of these parameters, we compared them with the following postnatal parameters: survival, pulmonary hypertension, need for oxygen supplementation, and need for extracorporeal membrane oxygenation. Results: We found significant differences between O/E LHR and the need for postnatal extracorporeal membrane oxygenation (P = .033) and postnatal survival (P = .01). We also found significant differences in LLSR between fetuses that survived more than 45 days and those that died within 45 days (1.91 vs. 2.56; P = .039). Conclusions: In fetuses with CDH, the LLSR correlates with postnatal survival and can potentially be used as a prognostic parameter in CDH (AU)

Symmorphosis in the proximal pathway for oxygen in the leaf-eared mouse Phyllotis darwini

In this report, we explore the matching of structures to functional needs by comparing previously reported data of maximal oxygen consumption and the development of the lung in the leaf-eared mouse Phyllotis darwini in warm and cold environments. We discuss whether the state of structural design is commensurate with functional needs from regulated morphogenesis as predicted by the hypothesis of symmorphosis. We found a close match between respiratory structures and functional needs during postnatal development, expressed as safety factors close to unity. However, in the adult stage the safety factors were greater than two, which suggests that adult animals acquired a structure greater than that required considering their maximum capacities. A high safety factor in the respiratory system of adult mice may be a consequence of the symmorphosis that operates during ontogeny and does not necessarily support a rejection of this hypothesis.