Neonatal Lung Disease Research Articles

Integrated MicroRNA-mRNA Analyses of Distinct Expression Profiles in Hyperoxia-Induced Bronchopulmonary Dysplasia in Neonatal Mice.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease of preterm neonates; the underlying pathogenesis is not fully understood. Recent studies suggested microRNAs (miRNAs) may be involved in BPD. miRNA and mRNA microarrays were performed to analyze the expression profiles of miRNA and mRNA in BPD and control lung tissues after oxygen and air exposure on day 21. Bioinformatics methods, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were performed to predict the potential functions of differentially expressed genes. Then, miRNA-mRNA regulatory network was constructed by protein-protein interaction (PPI) data and TarBase data. Our results showed that a total of 192 differentially expressed miRNAs (74 downregulated and 118 upregulated) and 1,225 differentially expressed mRNAs (479 downregulated and 746 upregulated) were identified between BPD mice and normoxia-control mice. GO and KEGG analysis showed that for downregulated genes, the top significant enriched GO terms and KEGG pathways were both mainly related to immune and inflammation processes; for upregulated genes, the top significant enriched GO terms and KEGG pathways were both mainly related to extracellular matrix (ECM) remodeling. PPI network and miRNA-mRNA regulatory network construction revealed that the key genes and pathways associated with inflammation and immune regulation. Our findings revealed the integrated miRNA-mRNA data of distinct expression profiles in hyperoxia-induced BPD mice, and may provide some clues of the potential biomarkers for BPD, and provide novel insights into the development of new promising biomarkers for the treatment of BPD. · Integrated advanced bioinformatics methods may offer a better way to understand the molecular expression profiles involved in BPD.. · ECM remodeling, inflammation, and immune regulation may be essential to BPD.. · The miRNA-mRNA regulatory network construction may contribute to develop new biomarkers for the treatment of BPD..

Genetic Testing for Neonatal Respiratory Disease.

Genetic mechanisms are now recognized as rare causes of neonatal lung disease. Genes potentially responsible for neonatal lung disease include those encoding proteins important in surfactant function and metabolism, transcription factors important in lung development, proteins involved in ciliary assembly and function, and various other structural and immune regulation genes. The phenotypes of infants with genetic causes of neonatal lung disease may have some features that are difficult to distinguish clinically from more common, reversible causes of lung disease, and from each other. Multigene panels are now available that can allow for a specific diagnosis, providing important information for treatment and prognosis. This review discusses genes in which abnormalities are known to cause neonatal lung disease and their associated phenotypes, and advantages and limitations of genetic testing.

Hydrogen Sulfide-Clues from Evolution and Implication for Neonatal Respiratory Diseases.

Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved in modulating the redox homeostasis in the developing lung. While animal data targeting aspects of these redox pathways have been promising in treating and/or preventing experimental models of neonatal lung disease, none are particularly effective in human neonatal clinical trials. In recent years, hydrogen sulfide (H2S) has emerged as a novel gasotransmitter involved in a magnitude of cellular signaling pathways and functions. The importance of H2S signaling may lie in the fact that early life-forms evolved in a nearly anoxic, sulfur-rich environment and were dependent on H2S for energy. Recent studies have demonstrated an important role of H2S and its synthesizing enzymes in lung development, which normally takes place in a relatively hypoxic intrauterine environment. In this review, we look at clues from evolution and explore the important role that the H2S signaling pathway may play in oxidative neonatal respiratory diseases and discuss future opportunities to explore this phenomenon in the context of neonatal chronic lung disease.

Perinatal inflammation relates to early respiratory morbidity and lung function at 12 years of age in children born very preterm.

Very preterm birth may be associated with lung function impairment later in life. It is not known if this is caused by prematurity per se or by associated perinatal events, such as maternal-foetal inflammation and severity of early neonatal lung disease. We assessed these factors in a prospective cohort of very preterm infants followed from birth to middle school age. In 71 infants with a gestational age of median 27.4 (range 23.9-31.7) weeks, pro-inflammatory and modulatory cytokines were measured in umbilical cord blood and in arterial blood sampled at 6, 24 and 72h after birth, and cumulated cytokine concentrations were calculated as area under the curve (AUC). At median 12.6 (range 12.3-13.5) years of age, pulmonary function testing was done in 53 children. There was a positive correlation between days on mechanical ventilation and AUC for IL-6 (p=0.001), IL-8 (p=0.015) and IL-10 (p=0.006). Infants with bronchopulmonary dysplasia (BPD; n=32) had higher AUC for the cytokines IL-6, IL-8 and IL-10 than those without BPD (all p<0.01). Higher levels of AUC for IL-6 at birth correlated with lower forced expiratory volume in 1s (p=0.030) and lower mean expiratory flow rate between 25 and 75% of forced vital capacity (p=0.034). Perinatal inflammation, assessed by circulating cytokines in the first three days of life, was associated with BPD and with airway obstruction at 12years of age.

Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease

IntroductionAlthough chronic pulmonary hypertension (cPH) secondary to chronic neonatal lung disease is associated with increased mortality and respiratory and neurodevelopmental morbidities, late diagnosis (typically ≥36 weeks postmenstrual age, PMA) and...

Predictors of home oxygen duration in chronic neonatal lung disease.

In infants with chronic neonatal lung disease (CNLD), we aimed to identify predictors of home oxygen duration, predictors of discharge oxygen flow rates, and the association of oxygen flow rates with respiratory outcomes. Infants with CNLD requiring home oxygen in 2016 and 2017 were retrospectively reviewed. Hazard ratios (HR) were estimated from Cox proportional hazards regression models in the cohort. A multinomial logistic regression model examined the effects of maternal and infant variables on discharge oxygen flow rates. Kruskal-Wallis test with univariate linear regression and Fisher's exact test with binomial univariate logistic regression were used to examine associations between oxygen flow groups and post-discharge clinical variables. One hundred and forty-nineinfants were included. Median corrected gestational age (CGA) at oxygen cessation was 6.8 months (interquartile range, 4.4) with 87.2% of infants weaned by 12 months CGA. Shorter initial neonatal intensive care unit (NICU) stay predicted faster oxygen weaning at 9 months (HR, 0.99; 95% confidence interval [CI], 0.98-1.00, p = .02) and 12 months (HR, 0.99; 95% CI, 0.98-1.00, p = .02). Infants with hypercarbia at discharge or discharged from NICU at higher CGA had higher odds of requiring ≥ 200 ml/min relative to ≤ 125 ml/min oxygen. Infants discharged with > 250 ml/min oxygen were more likely to have a respiratory-related admission before 2 years chronological age. Shorter initial NICU stay was the best predictor of earlier home oxygen cessation. At NICU discharge, infants with hypercarbia or a higher CGA may require more home oxygen and experience more respiratory-related hospital admission in the first 2 years of chronological age.

Biomarkers of Oxidative Stress for Neonatal Lung Disease.

The transition from prenatal to postnatal life causes a significant increase in arterial oxygen tension and the activation of metabolic pathways enabling the newborn's adaptation to the extra-uterine environment. The balance between pro-oxidant and anti-oxidant systems is critical to preserve cellular functions. Indeed, oxidative stress (OS) occurs when the production of free radicals is not balanced by the activity of intracellular antioxidant systems, contributing to cellular and tissue damage. Perinatal OS may have serious health consequences during the postnatal period and later in life. Namely, OS has been recognized as the major cause of lung injury in newborns, especially those preterm born, due to their immature lung and antioxidant systems. The development of OS biomarkers has gained increasing research interest since they may provide useful insights about pathophysiological pathways underlying OS-mediated pulmonary diseases in newborns. Moreover, their implementation in clinical settings may help to early identify high risk-newborns and to provide targeted treatment. Ideally, a biomarker should demonstrate ease of use, biological validity and reproducibility, high sensitivity and specificity. However, none of the clinically validated biomarkers so far have been qualified for neonatal lung disease. Additionally, the complex technical procedures and the high cost of such determinations have hampered the use of OS biomarkers in clinical practice. This review aims to evaluate the current evidence on the application of biomarkers of oxidative stress for neonatal lung disease and exploring the most relevant issues affecting their implementation in practice, as well as the associated evidence gaps and research limitations.

Hydroxychloroquine, a successful treatment for lung disease\xa0in ABCA3 deficiency gene mutation: a case report

BackgroundPulmonary surfactant is a complex mixture of lipids and specific proteins that stabilizes the alveoli at the end of expiration. Mutations in the gene coding for the triphosphate binding cassette transporter A3 (ABCA3), which facilitates the transfer of lipids to lamellar bodies, constitute the most frequent genetic cause of severe neonatal respiratory distress syndrome and chronic interstitial lung disease in children. Hydroxychloroquine can be used as an effective treatment for this rare severe condition.Case presentationWe report a late preterm Bosnian baby boy (36 weeks) who suffered from a severe form of respiratory distress syndrome with poor response to intensive conventional management and whole exome sequencing revealed homozygous ABCA3 mis-sense mutation. The baby showed remarkable improvement of the respiratory condition after the initiation of Hydroxychloroquine, Azithromycin and Corticosteroids with the continuation of Hydroxychloroquine as a monotherapy till after discharge from the hospital.ConclusionOutcome in patients with ABCA3 mutations is variable ranging from severe irreversible respiratory failure in early infancy to chronic interstitial lung disease in childhood (ChILD) usually with the need for lung transplantation in many patients surviving this rare disorder. Hydroxychloroquine through its anti-inflammatory effects or alteration of intra-cellular metabolism may have an effect in treating cases of ABCA3 gene mutations.

Correlation of Oxygen Saturation Index and Oxygenation Index in Hypoxaemic Respiratory Failure among Neonates

Introduction: Hypoxaemic Respiratory Failure (HRF) is severe arterial hypoxaemia that is refractory to supplemental oxygen. Oxygen Saturation Index (OSI) can be an alternate method of diagnosing and assessing the severity of HRF as it uses Oxygen Saturation (SpO2) in place of Partial Pressure of Oxygen (PaO2) and may be utilised with reasonable sensitivity and specificity. Aim: To evaluate the correlation between OSI and Oxygenation Index (OI) in HRF in neonates. Materials and Methods: The prospective observational study was conducted in Kempegowda Institute of Medical Sciences and Hospital, Bengaluru, Karnataka, India, from December 2016 to July 2018. Fifty neonates who were admitted to Neonatal Intensive Care Unit (NICU) and conventionally ventilated in view of HRF were included. Arterial blood gases in the first 24 hours of life and corresponding oxygen saturations and ventilator settings were recorded. OI and OSI was calculated using the standard formula and their correlation was analysed. Results: The neonates were all on first day of life at admission to NICU and were invasively ventilated due to HRF. The mean birth weight was 1.89±0.84 kg. Of the 50 neonates, 22 (44%) were preterm babies (&lt;34 weeks), 17 (34%) belonged to late preterm group (34 weeks to 36 weeks +6 days), 9 (18%) were term babies (&gt;37 weeks), two neonates were extremely preterm (less than 28 weeks). In this study, OSI and OI significantly associated and correlated (p-value &lt;0.01) with a correlation coefficient r=0.727. Area under the Receiver Operating Characteristic (ROC) curve for OSI was 0.912 which indicates that OSI is an excellent test to assess the severity of HRF. Conclusion: That OSI can be used to diagnose and assess the severity of lung disease in neonates having HRF.

Cystic lung diseases in neonates and infants

Cystic lung diseases in neonates and infants

The immunological link between neonatal lung and eye disease.

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two neonatal diseases of major clinical importance, arising in large part as a consequence of supplemental oxygen therapy used to promote the survival of preterm infants. The presence of coincident inflammation in the lungs and eyes of neonates receiving oxygen therapy indicates that a dysregulated immune response serves as a potential common pathogenic factor for both diseases. This review examines the current state of knowledge of immunological dysregulation in BPD and ROP, identifying similarities in the cellular subsets and inflammatory cytokines that are found in the alveoli and retina during the active phase of these diseases, indicating possible mechanistic overlap. In addition, we highlight gaps in the understanding of whether these responses emerge independently in the lung and retina as a consequence of oxygen exposure or arise because of inflammatory spill‐over from the lung. As BPD and ROP are anatomically distinct, they are often considered discreet disease entities and are therefore treated separately. We propose that an improved understanding of the relationship between BPD and ROP is key to the identification of novel therapeutic targets to treat or prevent both conditions simultaneously.

Sex and Gender Differences in Lung Disease.

Sex differences in the anatomy and physiology of the respiratory system have been widely reported. These intrinsic sex differences have also been shown to modulate the pathophysiology, incidence, morbidity, and mortality of several lung diseases across the life span. In this chapter, we describe the epidemiology of sexdifferences in respiratory diseases including neonatal lung disease (respiratory distress syndrome, bronchopulmonary dysplasia) and pediatric and adult disease (including asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, lymphangioleiomyomatosis, obstructive sleep apnea, pulmonary arterial hypertension, and respiratory viral infections such as respiratory syncytial virus, influenza, and SARS-CoV-2). We also discuss the current state of research on the mechanisms underlying the observed sex differences in lung disease susceptibility and severity and the importance of considering both sex and gender variables in research studies' design and analysis.

Echographie pulmonaire en réanimation pédiatrique : revue des connaissances en 2020

L’échographie pulmonaire (EP) s’est considérablement répandue en réanimation adulte mais son utilisation néonatale et pédiatrique, bien que croissante, reste plus limitée et la radiographie thoracique demeure l’examen de première ligne dans la plupart des centres. L’objectif de cette revue est de faire le point sur les études menées spécifiquement en réanimation pédiatrique, afin de présenter les connaissances déjà établies, les avantages et les limites de l’EP. Après un point sur son utilisation dans les pathologies néonatales et communautaires pédiatriques, nous abordons les utilisations spécifiques à la réanimation de l’enfant. L’EP présente un triple intérêt de diagnostic d’urgence, de guide aux procédures thérapeutiques et de suivi évolutif en temps réel ou différé. En néonatologie, elle aide à identifier l’étiologie des détresses respiratoires immédiates et secondaires et la gestion des détresses vitales. En pédiatrie communautaire, elle est utile au diagnostic de pneumonie et de bronchiolite et à la détection de complications. En réanimation pédiatrique, elle permet la mise en évidence des pneumopathies acquises sous ventilation mécanique (PAVM) et l’évaluation et le suivi du recrutement alvéolaire notamment dans le syndrome de détresse respiratoire aigüe (SDRA) ou les atélectasies péri opératoires. En combinaison avec le monitorage hémodynamique, elle aide à la surveillance des patients à risque d’oedème pulmonaire notamment dans les cardiopathies ou les sepsis. Enfin elle détecte rapidement les complications pulmonaires de réanimation ou post-opératoires, les atteintes thoraciques traumatiques et certaines causes potentiellement réversibles d’arrêt cardiaque. La publication récente des recommandations internationales pédiatriques et néonatales sur l’échographie d’urgence pourrait encourager sa diffusion dans la pratique courante.

Mendelian randomization and experimental IUGR reveal the adverse effect of low birth weight on lung structure and function

Intrauterine growth restriction (IUGR) and low birth weigth (LBW) are risk factors for neonatal chronic lung disease. However, maternal and fetal genetic factors and the molecular mechanisms remain unclear. We investigated the relationship between LBW and lung function with Mendelian randomisation analyses and studied angiogenesis in a low protein diet rat model of IUGR. Our data indicate a possible association between LBW and reduced FEV1 (p = 5.69E−18, MR-PRESSO) and FVC (6.02E-22, MR-PRESSO). Complimentary, we demonstrated two-phased perinatal programming after IUGR. The intrauterine phase (embryonic day 21) is earmarked by a reduction of endothelial cell markers (e.g. CD31) as well as mRNA expression of angiogenic factors (e.g., Vegfa, Flt1, Klf4). Protein analysis identified an activation of anti-angiogenic mTOR effectors. In the postnatal phase, lung capillaries (< 20 µm) were significantly reduced, expression of CD31 and VE-Cadherin were unaffected, whereas SMAD1/5/8 signaling and Klf4 protein were increased (p < 0.01). Moreover, elevated proteolytic activity of MMP2 and MMP9 was linked to a 50% reduction of lung elastic fibres. In conclusion, we show a possible link of LBW in humans and reduced lung function in adulthood. Experimental IUGR identifies an intrauterine phase with inhibition of angiogenic signaling, and a postnatal phase with proteolytic activity and reduced elastic fibres.

Mesenchymal stromal cell-derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation†.

Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of preclinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize that MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclampsia-like features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (Hmox1-/-) or wild-type control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day (GD)1 to Hmox1-/- females (Hmox1-/- MEx). Compared with untreated Hmox1-/- females, Hmox1-/- MEx-treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification, and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in Hmox1-/- MEx versus untreated pregnancies showed alteration in the abundance, surface marker repertoire, and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.

Lung ultrasound completely replaced chest X-ray for diagnosing neonatal lung diseases: a 3-year clinical practice report from a neonatal intensive care unit in China

Background and objective Lung ultrasound (LUS) has been widely used in the diagnosis and differential diagnosis of neonatal lung diseases (NLDs), but whether it can replace the routine use of chest X-ray (CXR) in neonatal intensive care units (NICUs) remains controversial. This paper summarizes the clinical practice of our neonatal intensive care unit (NICU) during the past three years to explore the feasibility and necessity of using LUS instead of CXR to diagnose NLDs in the NICU setting. Methods The clinical data and LUS examination results from 1,381 newborn infants with respiratory difficulty who were hospitalized in our NICU from March 2017 to February 2020 were retrospectively collected to analyze the types of lung diseases diagnosed and the reliability of LUS for diagnosing NLDs. Results (1) During this period, 1381 newborn infants with dyspnea were admitted to our NICU, accounting for 41.2% of all hospitalized children. (2) Among the 1381 infants, 17 patients with respiratory distress were confirmed as having severe heart disease by echocardiography, while the remaining 1364 patients had different kinds of lung diseases: pneumonia (697 patients, 51.1%), respiratory distress syndrome (251 patients, 17.4%), transient tachypnea of the newborn (197 patients, 13.3%), atelectasis (89 patients, 5.6%), pneumothorax (46 patients, 3.2%), pulmonary hemorrhage (69 patients, 4.5%), severe pleural effusion (18 patients, 1.32%), congenital pulmonary sequestration (3 patients, 0.22%), bullae of the lung (2 patients, 0.15%), and congenital cystic adenomatoid malformation (2 patients). (5) Among the 1381 infants, 217 received CXR examination before admission, which resulted in misdiagnosis in 45 patients (20.7%) and missed diagnosis in 12 patients (5.5%); the missed diagnosis and misdiagnosis rate was 26.3%. Conclusion Our 3-year clinical practice experience indicated that LUS could completely replace chest X-ray for the diagnosis and differential diagnosis of NLDs in the NICU. Compared with X-ray, LUS had higher accuracy and reliability in diagnosing NLDs.

Respiratory Severity Score greater than or equal to 2 at birth is associated with anincreased risk of mortality in infants with birth weightsless than or equal to 1250 g.

Respiratory Severity Score (RSS), the product of mean airway pressure andthe fraction of inspired oxygen may estimate the severity of neonatal lung disease. We aimed to determine if RSS on the first day of life is associated with mortality and/or comorbidities in infants born less than or equal to 1250 g. Data were extracted from the NYS Perinatal Data System for premature inborn infants from 2006 to 2016 born between 400 and 1250 g (N = 730). RSS was divided into three categories: less than 2 (low, n = 310), 2-5 (moderate, n = 265), greater than 5 (high, n = 155). The primary outcome was mortality. Logistic regression determined associations with composite outcomes of death or respiratory morbidity (respiratory support after 36 weeks postmenstrual age), death or neurologic morbidity (periventricular leukomalacia) or high-grade intraventricular hemorrhage), and death/severe morbidity (death or neurologic morbidity or respiratory morbidity or stage ≥ III retinopathy of prematurity or necrotizing enterocolitis) by RSS category. Birthweight and gestational age were lower with the increasing RSS category (p < .001 for both). Mode of delivery, antenatal steroids, and maternal age did not differ by RSS. In adjusted analyses, there were increased odds of mortality in infants with moderate RSS (odds ratio [95% confidence intervals]: 3.1 (1.7-5.4) and high 4.5 (2.5-8.2). These groups had higher odds of death or respiratory morbidity, death or neurologic morbidity, and death/severe morbidity. Higher RSS (≥2) is associated with an increased risk of mortality and morbidities in infants born less than or equal to 1250 g.

Histopathologic features of alveolar capillary dysplasia with misalignment of pulmonary veins with atypical clinical presentation

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare neonatal lung disease with fatal outcome. Typically, respiratory symptoms present in the first 24 hours of life and patients die within the neonatal period. Atypical, delayed clinical presentations and/or longer survival have also been reported. Here, we studied the clinicopathologic relationship of ACD/MPV by examining 16 cases of ACD/MPV, focusing on atypical features. Based on the presence of diffuse vs. focal/patchy ACD/MPV histopathologic changes, we divided the cases into classic and nonclassic pathology groups. MPV was found in all ACD/MPV. Ten of 16 cases exhibited classic diffuse abnormalities, while 6 of 16 had a nonclassic focal/patchy distribution. However, among 7 patients with atypical clinical features, only 2 had nonclassic pathology, while 4 out of 9 clinically typical cases had nonclassic ACD/MPV pathology. Marked intrapulmonary aberrant arteriovenous vessels were present in all atypical cases. In conclusion, clinical presentation is not always correlated with histopathology in ACD/MPV. Atypical ACD/MPV should be suspected in any infants with fulminant pulmonary hypertension. Abnormal pulmonary veins and aberrant intraseptal vessels are the most important clues for diagnosis. Additional studies are needed for further elucidation of diagnostic histological criteria of atypical ACD/MPV and to explore its pathogenesis.

Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia.

BackgroundThis study was undertaken to test the hypothesis that the newly synthesized curcuminoids B2BrBC and C66 supplementation will overcome hyperoxia‐induced tracheal hyperreactivity and impairment of relaxation of tracheal smooth muscle (TSM).Materials and methodsRat pups (P5) were exposed to hyperoxia (>95% O2) or normoxia for 7 days. At P12, tracheal cylinders were used to study in vitro contractile responses induced by methacholine (10−8–10−4M) or relaxation induced by electrical field stimulation (5–60 V) in the presence/absence of B2BrBC or C66, or to study the direct relaxant effects elicited by both analogs.ResultsHyperoxia significantly increased contraction and decreased relaxation of TSM compared to normoxia controls. Presence of B2BrBC or C66 normalized both contractile and relaxant responses altered by hyperoxia. Both, curcuminoids directly induced dose‐dependent relaxation of preconstricted TSM. Supplementation of hyperoxic animals with B2BrBC or C66, significantly increased catalase activity. Lung TNF‐α was significantly increased in hyperoxia‐exposed animals. Both curcumin analogs attenuated increases in TNF‐α in hyperoxic animals.ConclusionWe show that B2BrBC and C66 provide protection against adverse contractility and relaxant effect of hyperoxia on TSM, and whole lung inflammation. Both analogs induced direct relaxation of TSM. Through restoration of catalase activity in hyperoxia, we speculate that analogs are protective against hyperoxia‐induced tracheal hyperreactivity by augmenting H2O2 catabolism. Neonatal hyperoxia induces increased tracheal contractility, attenuates tracheal relaxation, diminishes lung antioxidant capacity, and increases lung inflammation, while monocarbonyl CUR analogs were protective of these adverse effects of hyperoxia. Analogs may be promising new therapies for neonatal hyperoxic airway and lung disease.

Bronchopulmonary dysplasia patients have preserved CT-measured central airway luminal area

Bronchopulmonary dysplasia (BPD) is a condition of neonatal chronic lung disease due to disruption or dysregulation of pulmonary development. However, the pathophysiology of BPD in the larger conducting airways is not yet fully understood. The objective of our study was to determine if the area of the central airways are altered in patients with a history of BPD. We hypothesized that compared to age- and sex-matched controls, BPD patients would have decreased area of the central conducting airways. Twenty-two BPD patients (n = 10 male, n = 12 female; median age = 10 [range:1–49] yrs) and n = 22 matched controls (n = 10 male, n = 12 female; median age = 10 [range:1–48] yrs) who had undergone a chest computed tomography (CT) scan were retrospectively identified. Measurement and analysis was performed using software that reconstructs the airways into 3D. Measurements of airway area were conducted at three points based on anatomic bifurcations for each of the following structures: trachea, left main bronchus, left upper lobe, left lower lobe, right main bronchus, intermediate bronchus, and right upper lobe. The luminal area for each airway was calculated based on the averages of the three measures. Airway luminal area was not different between BPD patients and matched controls for any of the measured airways (p > 0.05). Total lung volume detected in the CT scans was not different between BPD patients and matched controls (median [range]; 2775 [522–6215] vs 2969 [851–5612] cm3, p > 0.05). Our results suggest the luminal areas of the large conducting airways in patients with BPD are not different from matched controls.