Immature Lung Research Articles

CARD8: A Gas-Exchange-Area-Adjustable Oxygenator for Extremely Preterm Infants

Purpose: Worldwide, 600,000 infants are born extremely premature (EP) each year. Supporting the immature lungs of these smallest patients today using mechanical ventilation can cause severe lung damage. Extracorporeal gas exchange (ECMO) used as an “artificial placenta” is expected to provide an alternative treatment to allow full maturation of the lungs. The long-term application for patients doubling their weight every six weeks, requires a new type of “growing” oxygenator. Materials & Methods: We developed a gas-exchange-area-adjustable oxygenator that allows to operate at two different size stages without changing the device nor increasing the flow resistance. Our prototype houses two concentric oxygenator-chambers of equal gas exchange area. When the outer chamber is in operation, the oxygenator provides the required gas exchange area for a 24-week infant. Single-chamber operation allows adaequate gas exchange of volume flows from 50 - 125 ml/min while double-chamber operation then covers flow-demands from 125 - 200 ml/min. Both operational modes in combination can cover the needs of infants from 24 to 28 weeks postmenstrual age. We performed gas-transfer measurements of the prototype in accordance with ISO 7199 and FDA guideline. Results: Gas transport performance for the outer cylinder operating at Vblood = 50 mL/min (24 week premature infant) is VO2 = 1.8 mL/min (= 36 mLO2/Lblood flow). At a flow of Vblood = 125 mL/min the second chamber was switched on and the gas transfer performance increased by 50.1 %. Both chambers have a gas transport performance of VO2 = 4.19 ml/min at Vblood = 150 ml/min (= 28 mLO2/Lblood flow) Conclusion: It could be demonstrated that the gas-transfer of the newly proposed volume-adjustable oxygenator design is sufficient to increase the gas transfer performance while increasing the blood volume flow. We consider this a first milestone for oxygenation of growing EP infants without the need to replace the extracorporeal circuit, avoiding the associated risks.

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies.

Less invasive surfactant administration techniques, together with nasal continuous airway pressure (LISA-nCPAP) ventilation, an emerging noninvasive ventilation (NIV) technique in neonatology, are gaining more significance, even in extremely premature newborns (ELBW), under 27 weeks of gestational age. In this review, studies on LISA-nCPAP are compiled with an emphasis on short- and long-term morbidities associated with prematurity. Several perinatal preventative and therapeutic investigations are also discussed in order to start integrated therapies as numerous organ-saving techniques in addition to lung-protective ventilations. Two thirds of immature newborns can start their lives on NIV, and one third of them never need mechanical ventilation. With adjuvant intervention, these ratios are expected to be increased, resulting in better outcomes. Optimized cardiopulmonary transition, especially physiologic cord clamping, could have an additively beneficial effect on patient outcomes gained from NIV. Organ development and angiogenesis are strictly linked not only in the immature lung and retina, but also possibly in the kidney, and optimized interventions using angiogenic growth factors could lead to better morbidity-free survival. Corticosteroids, caffeine, insulin, thyroid hormones, antioxidants, N-acetylcysteine, and, moreover, the immunomodulatory components of mother's milk are also discussed as adjuvant treatments, since immature newborns deserve more complex neonatal interventions.

Evaluation of thalamus echogenicity via ultrasonography as a marker of fetal lung maturity

Background: Fetal lung immaturity is a major problem in the management of elective birth with respect to predicting the development of infant respiratory distress syndrome (IRDS) in the neonate after birth.Aim and Objectives: The aim of this study was to evaluate the validity of measuring fetal thalamic echogenicity by ultrasound as a marker of fetal lung maturity.Subjects and Methods: This was a prospective observational study that was being carried out on 80 pregnant patients. They were recruited from Obstetrics and Gynaecology clinics at Tanta University Hospitals during the period of research from March 2021 till the end of the study.Results: There was statistically significant difference between RDS group and those without RDS regarding thalamic echogenicity, 1 and 5- min APGAR score, NICU admission and neonatal mortality.Conclusion: Evaluation of echogenic thalamus by ultrasound at the level of the BPD is of value, and can be considered as a new marker of fetal lung maturity; however, further studies are required to strengthen such idea.

Evaluation of thalamus echogenicity via ultrasonography as a marker of fetal lung maturity

Background: Fetal lung immaturity is a major problem in the management of elective birth with respect to predicting the development of infant respiratory distress syndrome (IRDS) in the neonate after birth.Aim and Objectives: The aim of this study was to evaluate the validity of measuring fetal thalamic echogenicity by ultrasound as a marker of fetal lung maturity.Subjects and Methods: This was a prospective observational study that was being carried out on 80 pregnant patients. They were recruited from Obstetrics and Gynaecology clinics at Tanta University Hospitals during the period of research from March 2021 till the end of the study.Results: There was statistically significant difference between RDS group and those without RDS regarding thalamic echogenicity, 1 and 5- min APGAR score, NICU admission and neonatal mortality.Conclusion: Evaluation of echogenic thalamus by ultrasound at the level of the BPD is of value, and can be considered as a new marker of fetal lung maturity; however, further studies are required to strengthen such idea.

Ultrasonic evaluation of fetal lung development using deep learning with graph

BackgroundThe neonatal respiratory morbidity that was primarily caused by the immaturity of the fetal lung is an important clinical issue in close relation to the morbidity and mortality of the fetus. In clinics, the amniocentesis has been used to evaluate the fetal lung maturity, which is time-consuming, costly and invasive. As a non-invasive means, ultrasonography has been explored to quantitatively examine the fetal lung in the past decades. However, existing studies required the contour of the fetal lung which was delineated manually. This may lead to significant inter- and intra-observer variations. MethodsWe proposed a deep learning model for automated fetal lung segmentation and measurement, which was constructed combined U-Net with Graph model and pre-trained Vgg-16 network. The graph connection would extract stable feature for final segmentation and pre-trained method could speed up convergence.The model was trained with 3500 datasets augmented from 250 ultrasound images with both the fetal lung and heart delineated manually, and tested on 50 ultrasound images. In addition, the correlation between the size of fetal lung/heart as delineated by the model with gestational age was analyzed. ResultsThe fetal lung and cardiac area were segmented automatically with the accuracy, average Intersection over Union(IoU), sensitivity and precision being 0.991, 0.818, 0.909 and 0.888, respectively. In addition, the size of fetal lung/heart was well correlated with the gestational age, demonstrating good potentials for assessing the fetal development. ConclusionsThis study proposed a new robust method for automatic fetal lung segmentation in ultrasound images using Vgg16-GCN-UNet. Our proposed method could be utilized potentially not only to improve existing research in quantitative analyzing the fetal lung using ultrasound imaging technology, but also to alleviate the labor of the clinicians in routine measurement of the fetal lung/cardiac.

Neutrophil extracellular traps promote bronchopulmonary dysplasia-like injury in neonatal mice via the WNT/β-catenin pathway.

Bronchopulmonary dysplasia (BPD) is one of the most common and severe chronic diseases in preterm infants. Premature infants are susceptible to BPD due to immature lungs and adverse perinatal episodes of infection, hyperoxia, and mechanical ventilation. Neutrophils are the first line of host defence, and the release of neutrophil extracellular traps (NETs) is an important strategy to immobilize and kill invading microorganisms. This study examined whether NETs were associated with BPD in preterm infants and contributed to hyperoxia-induced lung injury in neonatal mice via the WNT/β-catenin pathway. In this study, we found that preterm infants with BPD had higher levels of NETs in their tracheal aspirates than those without BPD. Neonatal mice treated with NETs after birth exhibited BPD-like changes in their lungs. Furthermore, the levels of Aquaporin 5 (AQP5) and surfactant-associated protein C (SPC), which represent alveolar differentiation and development, were significantly lower than those in the controls. The WNT/β-catenin pathway is one of the most well-known signalling pathways involved in lung growth. We found that the expression of the target genes c-MYC, cyclin D, and vascular endothelial growth factor (VEGF) and the important proteins WNT3a and β-catenin significantly decreased. Moreover, heparin, which is a NET inhibitor, attenuated changes in gene and protein expression, thereby attenuating BPD-like changes. This finding indicates that NETs are associated with BPD and can induce BPD-like changes in neonatal mice via the WNT/β-catenin pathway.

Prediction of lung maturity through quantitative ultrasound analysis of fetal lung texture in women with diabetes during pregnancy.

The present study aimed to evaluate the performance of QuantusFLM® software, which performs quantitative ultrasound analysis of fetal lung texture, in predicting lung maturity in fetuses of diabetic mothers. The patients included in this study were between 34 and 38weeks and 6days gestation and were divided into two groups: (1) patients with diabetes on medication and (2) control. The ultrasound images were performed up to 48 h prior to delivery and analyzed using QuantusFLM® software, which classified each fetus as high or low risk for neonatal respiratory morbidity based on lung maturity or immaturity. A total of 111 patients were included in the study, being 55 in diabetes and 56 in control group. The pregnant women with diabetes had significantly higher body mass index (27.8 kg/m2 vs. 25.9 kg/m2, respectively, p=0.02), increased birth weight (3,135 g vs. 2,887 g, respectively, p=0.002), and a higher rate of labor induction (63.6 vs. 30.4 %, respectively, p<0.001) compared to the control group. QuantusFLM® software was able to predict lung maturity in diabetes group with 96.4 % accuracy, 96.4 % sensitivity and 100 % positive predictive value. Considering the total number of patients, the software demonstrated accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 95.5 , 97.2, 33.3, 98.1 and 25 %, respectively. QuantusFLM® was an accurate method for predicting lung maturity in normal and DM singleton pregnancies and has the potential to aid in deciding the timing of delivery for pregnant women with DM.

Premature monochorionic monoamniotic twins have lower lung compliance at birth than matched dichorionic diamniotic twins.

Premature infants are born with immature lungs that demonstrate abnormal pulmonary function with differences in passive respiratory system compliance and resistance, and functional residual capacity. To our knowledge, no studies have evaluated differences in neonatal pulmonary function based on the type of twin gestation, or chorionicity. Given the effect of chorionicity on outcomes, we aimed to study the effect of twin type, monochorionic monoamniotic (MCMA) vs dichorionic diamniotic (DCDA), on neonatal early pulmonary function tests. In this prospective cohort study, 5 sets of DCDA twins were matched to 5 sets of MCMA twins on gestational age at delivery, latency from antenatal corticosteroid exposure, birthweight, race and gender. Mean values were compared for passive respiratory system compliance and resistance, functional residual capacity, and tidal volume. MCMA infants had a significantly lower compliance (0.64 vs 1.25 mL/cm H2O /kg; p = 0.0001) and significantly higher resistance (0.130 vs 0.087 cm H2O /mL/sec; p = 0.0003) than DCDA infants. Functional residual capacity was lower for MCMA than DCDA infants (17.5 vs 23.4 mL/kg; p = 0.17). Further, 80% of MCMA infants required intubation for surfactant administration compared to 20% of DCDA infants, indicating the clinical significance of these objective measures. Due to the matched case-control design, causality cannot be established. However, we speculate that these differences in lung function may derive from differential exposure to preterm labor and endogenous maternal corticosteroid exposure. Further study is necessary to establish the true causal relationship.

Lung dopaminergic nerves facilitate the establishment of TH2 resident memory cells in early life

Allergic asthma develops from allergen exposure in early childhood and progresses into adulthood. The central mediator of progressive allergic asthma is allergen-specific, TH2-resident memory cells (TRMs). Although the crosstalk between nerves and immune cells plays an established role in acute allergic inflammation, whether nerves facilitate the establishment of TH2-TRMs in the immature lung following early life allergen exposure is unknown. The aim of this study was to identify nerve-derived signals that act in TH2 effector cells to regulate the tissue residency in the immature lung. Following neonatal allergen exposure, allergen-specific TH2-TRMs were tracked temporally and spatially in relationship to developing sympathetic nerves in the lung. Functional mediators of dopamine signaling in the establishment of TH2-TRMs were identified by invitro bulk RNA-sequencing of dopamine-treated TH2 cells followed by invivo assessment of candidate genes using adoptive transfer of TH2 cells with viral gene knockdown. This study found that sympathetic nerves produce dopamine and reside in proximity to TH2 effector cells during the contraction phase following neonatal allergen exposure. Dopamine signals via DRD4 on TH2 cells to elevate IL2RA and epigenetically facilitate type 2 cytokine expression. Blockade of dopamine-DRD4 signaling following neonatal allergen exposure impairs lung residence of TH2 cells and ameliorates anamnestic inflammation in adults. These results demonstrate that maturing sympathetic nerves enable a dopamine-enriched lung environment in early life that promotes the establishment of allergen-specific TH2-TRMs. The dopamine-DRD4 axis may provide a therapeutic target to modify allergic asthma progression from childhood to adulthood.

Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during postnatal growth

At birth, the lung is still immature, heightening susceptibility to injury but enhancing regenerative capacity. Angiogenesis drives postnatal lung development. Therefore, we profiled the transcriptional ontogeny and sensitivity to injury of pulmonary endothelial cells (EC) during early postnatal life. Although subtype speciation was evident at birth, immature lung EC exhibited transcriptomes distinct from mature counterparts, which progressed dynamically over time. Gradual, temporal changes in aerocyte capillary EC (CAP2) contrasted with more marked alterations in general capillary EC (CAP1) phenotype, including distinct CAP1 present only in the early alveolar lung expressing Peg3, a paternally imprinted transcription factor. Hyperoxia, an injury that impairs angiogenesis induced both common and unique endothelial gene signatures, dysregulated capillary EC crosstalk, and suppressed CAP1 proliferation while stimulating venous EC proliferation. These data highlight the diversity, transcriptomic evolution, and pleiotropic responses to injury of immature lung EC, possessing broad implications for lung development and injury across the lifespan.

One-Carbon Metabolism, a Nutrient Dependent Mediator of Angiogenesis and Alveolar Formation in the Developing Lung

Background/Objective: Lung maturation has discrete dynamic shifts in metabolic derivatives that give rise to stage specific metabolite signatures. Components of one-carbon metabolism (OCM) are significantly increased in the late saccular and alveolar stage while hyperoxia disrupts OCM metabolism during these lung developmental stages. We hypothesize that disrupted OCM metabolites in the immature lung disrupts vessel dependent alveolar formation thus contributing to alveolar dysplasia. Our studies explore the impact that restoration of OCM has on angiogenesis and alveolar formation.Methods: Isolated human neonatal circulating Endothelial Colony Forming Cells (ECFCs) were examined for proliferation (WST-1), migration (scratch assay), and angiogenesis (matrigel) in response to supplementation of OCM derivatives, essential amino acid methionine and nicotinamide. OCM enzyme levels were assessed via Western blotting, NNMT, NAMPT, DNMT. Lastly, alveolar formation in a hyperoxia murine model of prematurity (HMMP) with dietary supplement of methionine vs control was assessed, MLI, H&amp;E, and vessel formation (endomucin).Results: Methionine and nicotinamide increased ECFC proliferation (p&lt;0.05) and OCM enzymes. Nicotinamide increased ECFC angiogenesis (p&lt;0.05). ECFC migration was not impacted by methionine or nicotinamide supplementation (p NS). Methionine dietary supplementation in a HMMP model improved distal alveolar formation.Conclusion and Clinical Implications: Lung maturation is dependent on shifting metabolic needs during development. Replenishment of disrupted key OCM metabolites in HMMP promotes vessel and alveolar formation. Future studies are necessary to explore the role of precision nutritive supplementation in alveolar development of premature infants.

Investigation of urinary β2 microglobulin; substitute for interferon-γ as a suppressor of pulmonary fibrosis in a preterm with chronic lung disease following intrauterine infection

We experienced a female infant weighing 866 g at birth after 28 weeks 1 day gestation with apparent intrauterine infection. Bi-level-nasal CPAP was selected for respiratory management as a strategy to minimize the severity of chronic lung disease (CLD). As a result, she survived the acute phase without tracheal intubation and improved without requiring home oxygen therapy. Her urinary β2 microglobulin (u-BMG) in the early neonatal period was less than the cutoff value of 100,000 μg/gCr for the onset of CLD. However, her u-BMG then rose to a markedly high value that peaked at 3 weeks after birth. Her serum KL-6 was markedly high early after birth and increased sharply to a peak of 3016 U/mL on day 9. The increase in KL-6 in the early postnatal period indicated that lung tissue had already been injured by intrauterine inflammation, and although postnatal tracheal intubation was avoided, spontaneous breathing inevitably additionally injured the immature lung. It appears that substantial repair had occurred with fibrosis. It should be noted that the peak of u-BMG was delayed by more than 10 days from the peak of KL-6. This may suggest that the inflammatory cytokine interferon-γ, which increases the production of BMG, had not only an inflammatory effect that exacerbates lung damage, but also a biological self-defense effect that mainly suppresses lung fibrosis.

Exploring right ventricular function applicability in a prediction model to identify preterm infants with early bronchopulmonary dysplasia (REPORT-BPD study): a mixed-methods observational cohort feasibility study protocol.

Bronchopulmonary dysplasia (BPD) is a chronic disease that affects the immature lungs of preterm infants. Infants born before 32 weeks of gestation are at a greater risk of developing BPD due to the need for respiratory support with higher oxygen requirement. Pulmonary vascular remodelling in early BPD can impose an additional burden on the right ventricle (RV) and RV dysfunction. This protocol outlines the study design and aims to formulate a prediction model to identify early BPD through the data generated from echo scans analysis. The mixed-methods observational cohort feasibility study, which comprises three work-packages (WPs), will be conducted at the regional neonatal unit, University Hospital Plymouth, Plymouth, UK. WP-I will recruit 40 preterm infants; each participant will have two heart scans performed in the first ten days after birth (DABs). WP-II will collect the documentation of the participating preterm infants' parents in the study neonatal unit diaries in the first 10 DABs. WP-III will involve semi-structured interviews of 10-15 parents of participating preterm infants and 10-15 health professionals who participated in WP-I. The study recruitment will be conducted over 18-months. The start date is 01 June 2022. WP-I and WP-II recruitment will occur during this period, while WP-III recruitment will occur during the second half. The results are expected to be submitted for publication by mid-2024. This paper outlines the study design. If the study successfully identifies the most sensitive echo parameter in recognising the RV dysfunction associated with early BPD, it will be an important finding in constructing an early BPD prediction model. ClinicalTrials.gov Identifier is NCT05235399.

Agenesis of the left hemi-diaphragm, the cause of a neglected dyspnea in a 65-year-old female; case report and literature review

In its complex way of embryonic evolvement, the diaphragmatic membrane can be involved with various disorders that may partially or entirely not develop. Agenesis of the diaphragm is the term that refers to this maldevelopment. It is the more severe form of congenital diaphragmatic hernia in which intra-abdominal viscera protrude into the thoracic cavity, causing respiratory and gastrointestinal problems. Most neonates delivered with diaphragmatic agenesis do not live more than hours to days of the severity of lung immaturity. However, less than 20 affected cases have been reported so far that survived to childhood and even their adulthood period treated surgically or conservatively. We have reported a case of neglected left hemi-diaphragmatic agenesis for more than six decades, then reviewed all adult diaphragmatic agenesis cases available in the literature for 74 years. A 65-year-old female complaining of worsened dyspnea during the last four months, a chronic history of short breath since her fourth decade of life, and recent surgery with the diagnosis of a diaphragmatic hernia, underwent the thoracotomy twice in which unilateral diaphragmatic hernia was diagnosed then repaired. For the recurrence of her symptoms, she underwent a second thoracotomy, in which the final diagnosis of left hemi-diaphragmatic agenesis was made. A dual mesh patch constructed the defect. The post-operation period was uneventful. We only found 17 cases of adult hemi or bilateral agenesis of the diaphragm reviewing the main medical literature such as Medline and Web of Science. The conservative and operative treatment managements were equal for eight patients in each of them. One of them refused therapy, and one was non-declared in the study. As in congenital diaphragmatic hernia, the most typical side was the left in 10 out of 18. The most complaints patients had followed by coughing and bowel obstruction was dyspnea and dyspepsia. Near the total of the diaphragmatic agenesis cases die in the neonatal population; remained undiagnosed or during an autopsy found. However, typically rare in the adult population, respiratory and digestive disorders are the most prevalent. It is difficult initially because diagnosing is intraoperatively, and no modality is available to help the examiner physician diagnose perinatally.

Decoding the IGF1 signaling gene regulatory network behind alveologenesis from a mouse model of bronchopulmonary dysplasia.

Lung development is precisely controlled by underlying gene regulatory networks (GRN). Disruption of genes in the network can interrupt normal development and cause diseases such as bronchopulmonary dysplasia (BPD) - a chronic lung disease in preterm infants with morbid and sometimes lethal consequences characterized by lung immaturity and reduced alveolarization. Here, we generated a transgenic mouse exhibiting a moderate severity BPD phenotype by blocking IGF1 signaling in secondary crest myofibroblasts (SCMF) at the onset of alveologenesis. Using approaches mirroring the construction of the model GRN in sea urchin's development, we constructed the IGF1 signaling network underlying alveologenesis using this mouse model that phenocopies BPD. The constructed GRN, consisting of 43 genes, provides a bird's eye view of how the genes downstream of IGF1 are regulatorily connected. The GRN also reveals a mechanistic interpretation of how the effects of IGF1 signaling are transduced within SCMF from its specification genes to its effector genes and then from SCMF to its neighboring alveolar epithelial cells with WNT5A and FGF10 signaling as the bridge. Consistently, blocking WNT5A signaling in mice phenocopies BPD as inferred by the network. A comparative study on human samples suggests that a GRN of similar components and wiring underlies human BPD. Our network view of alveologenesis is transforming our perspective to understand and treat BPD. This new perspective calls for the construction of the full signaling GRN underlying alveologenesis, upon which targeted therapies for this neonatal chronic lung disease can be viably developed.

Respiratory distress syndrome in preterm infants: possible impact of surfactant application techniques.

Prematurity is one of the most important issues in perinatology. The most frequent postnatal pathology connected with prematurity is respiratory distress syndrome (RDS) caused by surfactant deficiency due to lung immaturity. RDS is one of the most frequent causes of mortality and morbidity with short- and long-term consequences. The aim of the study was to compare the effectiveness of individual surfactant supply techniques in the treatment of respiratory disorders in premature infants. In the period from the year 2009 to 2013, there were 198 very premature infants that received surfactant included to this retrospective study. They were divided into three groups based on the surfactant application method: Premature newborns with substitute ventilation, with supply of surfactant through a traditional endotracheal tube - Average gestational age 26.6 weeks; Mean birth weight 911 g; Average Apgar score 4 in 1st minute, 6 in 5th minute. Premature newborns with exogenous surfactant supplementation - InSure method - Average gestational age 28.3 weeks; Average birth weight 1117 g; Mean Apgar score 6 in 1st minute, 7 in 5th minute. Premature newborns with exogenous surfactant supplementation - Less Invasive Surfactant Administration (LISA) method - Mean gestational age 29.9 weeks; Average birth weight 1444 g; Average Apgar score 7 in 1st minute, 8 in 5th minute. Noninvasive methods of respiratory support and minimally invasive surfactant administration (MISA) significantly reduced the incidence of severe RDS, compared to the traditional method. Non-invasive methods of respiratory support and MISA like LISA and InSure methods were safe and effective in the treatment of RDS.

POSSIBILITIES OF RADIOGRAPHY IN THE DIAGNOSIS OF PNEUMONIA IN NEWBORNS

The features of X-ray semiotics in pneumonia in newborns were evaluated depending on the gestational age at birth. Conducted clinical and radiological examination of newborns with pneumonia. Plain chest radiography was used from radiographic methods. In the group of full-term newborns without signs of intrauterine growth retardation with pneumonia, changes prevailed that were mainly characteristic of the I degree of severity of the respiratory distress syndrome, namely, miliary spotting, limited low-intensity inhomogeneous darkening, blurry nodose-reticular mesh, and a distinguishable "air bronchogram". In full-term newborns with signs of intrauterine growth retardation, changes characteristic of I and II degrees of severity of the respiratory distress syndrome prevailed in equal proportions, that is, a decrease in pneumatization, coarse randomly scattered areas of lung tissue compaction and "air bronchograms". In preterm newborns, depending on the depth of prematurity, and possibly due to a short-term clinically asymptomatic onset, in most cases, II and III degrees of severity of the respiratory distress syndrome were noted at admission: a pronounced decrease in pneumatization (“frosted glass”), smoothing of the pulmonary-diaphragmatic and pulmonary -cardiac border (positive "silhouette" symptom), air bronchograms. The distribution of children according to clinical and radiological signs depends on gestational age, and atelectatic pneumonia is most often recorded in premature babies against the background of morphofunctional immaturity of the lungs. The deeper the prematurity, the more pronounced the influence of immature lung tissue on the occurrence and course of the inflammatory process in the lungs, and the inflammatory process becomes rapid, spreading to a large area of ​​the lungs.

Respiratory distress syndrome management in resource limited settings-Current evidence and opportunities in 2022.

The complications of prematurity are the leading cause of neonatal mortality worldwide, with the highest burden in the low- and middle-income countries of South Asia and Sub-Saharan Africa. A major driver of this prematurity-related neonatal mortality is respiratory distress syndrome due to immature lungs and surfactant deficiency. The World Health Organization's Every Newborn Action Plan target is for 80% of districts to have resources available to care for small and sick newborns, including premature infants with respiratory distress syndrome. Evidence-based interventions for respiratory distress syndrome management exist for the peripartum, delivery and neonatal intensive care period- however, cost, resources, and infrastructure limit their availability in low- and middle-income countries. Existing research and implementation gaps include the safe use of antenatal corticosteroid in non-tertiary settings, establishing emergency transportation services from low to high level care facilities, optimized delivery room resuscitation, provision of affordable caffeine and surfactant as well as implementing non-traditional methods of surfactant administration. There is also a need to optimize affordable continuous positive airway pressure devices able to blend oxygen, provide humidity and deliver reliable pressure. If the high prematurity-related neonatal mortality experienced in low- and middle-income countries is to be mitigated, a concerted effort by researchers, implementers and policy developers is required to address these key modalities.

Anaesthetic Management of 2 Micropreemies with Difficult Airway: Case Report and Review of Literature.

The infants are explicitly vulnerable to develop anaesthesia-related complications, with micropreemies being at the end of the spectrum because of their unique morphological and physiological features. Airway changes in pediatric patients are most exaggerated in these tiny infants and their immature lungs provide a little reserve, and therefore, securing airways can be challenging in this population. Moreover, many devices available for managing difficult airways in adults are not available for use in this miniature version. Videolaryngoscopes are a useful addition to anaesthesiologists’ armamentarium but for micropreemies, size of videolaryngoscope can be a limiting factor as no videolaryngoscope comes in “00” size. The technique of videolaryngoscope may need to be modified in these patients. Regional anaesthesia can be an invaluable component of their perioperative care to facilitate a smooth recovery. The successful management of these vulnerable neonates requires a multidisciplinary team approach to maintain perioperative homeostasis of their immature organ systems.

TRAIL protects the immature lung from hyperoxic injury

The hyperoxia-induced pro-inflammatory response and tissue damage constitute pivotal steps leading to bronchopulmonary dysplasia (BPD) in the immature lung. The pro-inflammatory cytokines are considered attractive candidates for a directed intervention but the complex interplay between inflammatory and developmental signaling pathways requires a comprehensive evaluation before introduction into clinical trials as studied here for the death inducing ligand TRAIL. At birth and during prolonged exposure to oxygen and mechanical ventilation, levels of TRAIL were lower in tracheal aspirates of preterm infants <29 weeks of gestation which developed moderate/severe BPD. These findings were reproduced in the newborn mouse model of hyperoxic injury. The loss of TRAIL was associated with increased inflammation, apoptosis induction and more pronounced lung structural simplification after hyperoxia exposure for 7 days while activation of NFκB signaling during exposure to hyperoxia was abrogated. Pretreatment with recombinant TRAIL rescued the developmental distortions in precision cut lung slices of both wildtype and TRAIL−/− mice exposed to hyperoxia. Of importance, TRAIL preserved alveolar type II cells, mesenchymal progenitor cells and vascular endothelial cells. In the situation of TRAIL depletion, our data ascribe oxygen toxicity a more injurious impact on structural lung development. These data are not surprising taking into account the diverse functions of TRAIL and its stimulatory effects on NFκB signaling as central driver of survival and development. TRAIL exerts a protective role in the immature lung as observed for the death inducing ligand TNF-α before.