Infant Lung Research Articles

Sustained Inflation Versus Intermittent Positive Pressure Ventilation for Preterm Infants at Birth: Respiratory Function and Vital Sign Measurements

To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered noninvasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms. We analyzed RFM data from SAIL participants at 5 trial sites. We assessed tidal volumes, rates of airway obstruction, and mask leak among infants allocated to sustained inflations and IPPV, and we compared pulse rate and oxygen saturation measurements between treatment groups. Among 70 SAIL participants (36 sustained inflations, 34 IPPV) with RFM measurements, 40 (57%) were spontaneously breathing prior to the randomized intervention. The median expiratory tidal volume of sustained inflations administered was 5.3mL/kg (IQR 1.1-9.2). Significant mask leak occurred in 15% and airway obstruction occurred during 17% of sustained inflations. Among 34 control infants, the median expiratory tidal volume of IPPV inflations was 4.3mL/kg (IQR 1.3-6.6). Mask leak was present in 3%, and airway obstruction was present in 17% of IPPV inflations. There were no significant differences in pulse rate or oxygen saturation measurements between groups at any point during resuscitation. Expiratory tidal volumes of sustained inflations and IPPV inflations administered in the SAIL trial were highly variable in both treatment arms. Vital sign values were similar between groups throughout resuscitation. Sustained inflation as operationalized in the SAIL trial was not superior to IPPV to promote lung aeration after birth in this study subgroup. Clinicaltrials.gov: NCT02139800.

Are children born by cesarean delivery at higher risk for respiratory sequelae?

Globally, the number of children born by cesarean delivery is constantly increasing. However, hormonal and physiological changes associated with labor and vaginal delivery are considered necessary for lung maturation. We aimed to assess whether the mode of delivery is associated with changes in respiratory and atopic outcomes during infancy and at school age. We included 578 children, born at ≥37 weeks of gestation, from a prospective birth cohort study. We compared weekly respiratory symptoms throughout the first year of life and infant lung function (tidal breathing and multiple-breath washout) at 5 weeks of age between children born by cesarean delivery (N=114) and those born by vaginal delivery (N=464) after term pregnancy in healthy women. At a follow-up visit conducted at 6 years of age (N=371, of which 65 were delivered by cesarean delivery), we assessed respiratory, atopic, and lung function outcomes (spirometry, body plethysmography, and multiple-breath washout). We performed adjusted regression analyses to examine the association between cesarean delivery and respiratory and atopic outcomes. To account for multiple testing, we used the Bonferroni correction, which led to an adapted significance level of P<.002. During infancy, children born by cesarean delivery did not have more respiratory symptoms than those born by vaginal delivery (median, 4 weeks; interquartile range, 7 weeks vs median, 5 weeks; interquartile range, 7 weeks; adjusted incidence rate ratio, 0.8; 95% confidence interval, 0.6-1.0; P=.02). Infant lung function was similar between the groups. Children born by cesarean delivery did not have a higher incidence of "ever wheezing" (adjusted odds ratio, 0.9; 95% confidence interval, 0.5-1.8; P=.78) or current asthma (adjusted odds ratio, 0.4; 95% confidence interval, 0.0-3.5; P=.42) at school age than those born by vaginal delivery. There was no difference in the lung function parameters between the groups. Cesarean delivery was not associated with respiratory symptoms in the first year of life, nor with different respiratory oratopic outcomes at school age, when compared with vaginal delivery. Our results indicate that there are no long-term consequences on the respiratory health of the child associated with cesarean delivery.

Associations of air pollution and greenness with the nasal microbiota of healthy infants: A longitudinal study

BackgroundAir pollution and greenness are associated with short- and long-term respiratory health in children but the underlying mechanisms are only scarcely investigated. The nasal microbiota during the first year of life has been shown to be associated with respiratory tract infections and asthma development. Thus, an interplay between greenness, air pollution and the early nasal microbiota may contribute to short- and long-term respiratory health. We aimed to examine associations between fine particulate matter (PM2.5), nitrogen dioxide (NO2) and greenness with the nasal microbiota of healthy infants during the first year of life in a European context with low-to-moderate air pollution levels. MethodsMicrobiota characterization was performed using 16 S rRNA pyrosequencing of 846 nasal swabs collected fortnightly from 47 healthy infants of the prospective Basel-Bern Infant Lung Development (BILD) cohort. We investigated the association of satellite-based greenness and an 8-day-average exposure to air pollution (PM2.5, NO2) with the nasal microbiota during the first year of life. Exposures were individually estimated with novel spatial-temporal models incorporating satellite data. Generalized additive mixed models adjusted for known confounders and considering the autoregressive correlation structure of the data were used for analysis. ResultsMean (SD) PM2.5 level was 17.1 (3.8 μg/m3) and mean (SD) NO2 level was 19.7 (7.9 μg/m3). Increased PM2.5 and increased NO2 were associated with reduced within-subject Ružička dissimilarity (PM2.5: per 1 μg/m3 -0.004, 95% CI -0.008, −0.001; NO2: per 1 μg/m3 -0.004, 95% CI -0.007, −0.001). Whole microbial community comparison with nonmetric multidimensional scaling revealed distinct microbiota profiles for different PM2.5 exposure levels. Increased NO2 was additionally associated with reduced abundance of Corynebacteriaceae (per 1 μg/m3: −0.027, 95% CI -0.053, −0.001). No associations were found between greenness and the nasal microbiota. ConclusionAir pollution was associated with Ružička dissimilarity and relative abundance of Corynebacteriaceae. This suggests that even low-to-moderate exposure to air pollution may impact the nasal microbiota during the first year of life. Our results will be useful for future studies assessing the clinical relevance of air-pollution-induced alterations of the nasal microbiota with subsequent respiratory disease development.

Gas in scattering media absorption spectroscopy on small and large scales: Toward the extension of lung spectroscopic monitoring to adults

AbstractNumerous natural materials are porous, contain free gas and are scattering light strongly. Scattering brings about a strong trapping of light and an associated prolonged transit time for photons through a medium. In contrast to the matrix materials, gas enclosures require very narrowband laser radiation for probing. We have in the present study used the gas in scattering media absorption spectroscopy method to study free oxygen in thin (cm) samples utilizing a tunable diode laser, while a pulsed dye laser was employed in corresponding measurements on larger samples, up to the meter scale. Time‐resolved spectroscopy was in both cases used to assess the temporal distribution of the detected photons, mapping the path lengths through the media, which ranged between few centimeters up to 100 m. This study explores the feasibility to extend recent successful monitoring of gases in neonatal infant lungs to the case of larger children or even adults, which could have very important applications, for example, in ventilator setting optimization for severely ill patients, suffering, for example, from SARS‐CoV‐2. The conclusion of our work is that this goal most realistically can be reached by applying intratracheal laser light illumination at the 1 W power level, employing a tapered amplifier, injected with a distributed feedback diode‐laser oscillator output and combined with wavelength‐modulation spectroscopy.

Neonatal Resuscitation With T-Piece Systems: Risk of Inadvertent PEEP Related to Mechanical Properties.

Background: Resuscitation of infants using T-piece resuscitators (TPR) allow positive pressure ventilation with positive end-expiratory pressure (PEEP). The adjustable PEEP valve adds resistance to expiration and could contribute to inadvertent PEEP. The study indirectly investigated risk of inadvertent peep by determining expiratory time constants. The aim was to measure system expiratory time constants for a TPR device in a passive mechanical model with infant lung properties.Methods: We used adiabatic bottles to generate four levels of compliance (0.5–3.4 mL/cm H2O). Expiratory time constants were recorded for combinations of fresh gas flow (8, 10, 15 L/min), PEEP (5, 8, 10 cm H2O), airway resistance (50, 200 cm H2O/L/sec and none), endotracheal tube (none, size 2.5, 3.0, 3.5) with a peak inflation pressure of 15 cm H2O above PEEP.Results: Low compliances resulted in time constants below 0.17 s contrasting to higher compliances where the expiratory time constants were 0.25–0.81 s. Time constants increased with increased resistance, lower fresh gas flows, higher set PEEP levels and with an added airway resistance or endotracheal tube.Conclusions: The risk of inadvertent PEEP increases with a shorter time for expiration in combination with a higher compliance or resistance. The TPR resistance can be reduced by increasing the fresh gas flow or reducing PEEP. The expiratory time constants indicate that this may be clinically important. The risk of inadvertent PEEP would be highest in intubated term infants with highly compliant lungs. These results are useful for interpreting clinical events and recordings.

Neonates with coronavirus disease 2019 acquired from infected mothers: the incompatibility of maternal intensity and infant lung involvement: two\xa0case reports

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a public health emergency by the World Health Organization on January 30, 2020. The results of recent studies have suggested that neonates may present symptoms of COVID-19. Although the presentation of the disease in neonates is known to vary, only a limited number of studies have investigated newborns infected with COVID-19.Case presentationThis study presents two Asian cases of newborns with COVID-19. Maternal–fetal or postnatal transmission was suggested based on the simultaneity of maternal infection. Chest radiography in one of the neonates showed severe lung involvement. Despite support and resuscitation attempts, the poor clinical condition of the neonate led to his death. However, the two mothers and one of the neonates were discharged from the hospital in good general condition.ConclusionThe neonates had worse clinical conditions than the mothers, and the intensity of pneumonia and level of lung involvement in the newborns were not associated with the stage and severity of the disease in the mothers with COVID-19.

Improved Outcomes of Infant Lung Transplantation Over 3 Decades

BackgroundLung transplantation is the definitive surgical treatment for end-stage lung disease. However, infants comprise less than 5% of pediatric cases. This study sought to provide an overview of infant lung transplantation outcomes over the past 3 decades by using linked United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) data. MethodsInfants undergoing lung transplantation from 1989 to 2020 in UNOS were reviewed. UNOS and PHIS records for patients who underwent lung transplantation from 1995 to 2020 were linked using date of birth, sex, and date of surgery ± 3 days. The study assessed underlying diagnoses, pretransplant and posttransplant extracorporeal membrane oxygenation support, retransplant-free survival to discharge, hospital experience (≥1 annual transplant for ≥4 years in a 5-year period), operative decade, bronchiolitis obliterans syndrome, long-term survival, and functional status at latest follow-up. ResultsA total of 112 lung transplants were performed in 109 infants over 31 years. Of these, 21 patients died before discharge, and 2 underwent repeat transplantation during the same admission. The study linked 80.6% (83 of 103) of UNOS and PHIS records. Hospital survival was lower for infants with idiopathic pulmonary hypertension and those who underwent transplant procedures at less experienced centers. All 7 infants requiring postoperative extracorporeal membrane oxygenation support died. Median freedom from bronchiolitis obliterans syndrome was 8.1 years (interquartile range, 4.6 to 11.6 years). After discharge, median survival was 10.3 years (interquartile range, 6.3 to 14.4 years), with improved 10-year survival for those patients who underwent transplantation from 2010 to 2020 (87.3%) vs 2000 to 2009 (52.4%; P = .098) and 1989 to 1999 (34.1%; P = .004). A total of 84.6% (33 of 39) of survivors had minor or no restrictions at latest follow-up. ConclusionsCarefully selected infants experience promising short- and long-term outcomes after lung transplantation.

Distinct lung function and bronchodilator responses between term and preterm young children with recurrent wheezing

Recurrent or unresolved wheezing is a common complaint in certain young children populations, especially those born preterm. Using infant lung function testing, we aimed to distinguish the differences between term and preterm young children with recurrent wheezing. Children under 2 years of corrected age were enrolled if they had 3 or more wheezing episodes during the enrollment period. Healthy term controls of comparable age were also recruited for reference. Measurements of lung function were made, including tidal breathing, passive respiratory mechanics, and forced tidal and raised-volume expiration. For children with recurrent wheezing, raised-volume forced expiration was repeated after an adequate delivery of bronchodilator nebulization was achieved. In total, 68 young children (40 with recurrent wheezing and 28 healthy controls) were recruited. Among children with recurrent wheezing, 23 preterm children (preterm group), and 17 term children (term group) were enrolled. Compared with healthy controls, both the term and preterm groups had lower lung function as measured by absolute values and z scores. The term group performed worse than the preterm group with regard to forced vital capacity, forced expiratory volume at 0.5s (FEV0.5), and peak expiratory flow. Following bronchodilator nebulization, the term group had significantly higher increases in FEV0.5 and forced mid-expiratory flow than the preterm group. Young children with recurrent wheezing, especially term infants, demonstrated lower lung function than healthy controls. Moreover, the term group evidenced greater responsiveness to bronchodilators than the preterm group. The distinct bronchodilator responses may offer further information to guide the diagnosis and treatment of young children with recurrent wheezing.

Ghrelin Expression in Mast Cells of Infant Lung with Respiratory Distress Syndrome

Abstract This article sheds light on some features of ghrelin (GHR)- and tryptase (Try)-positive mast cells (MCs) distribution in human lung of preterm newborns with respiratory distress syndrome (RDS). GHR possessed anti-inflammatory activity and reliable therapeutic properties in some lung diseases. So far, GHR expression has been defined predominantly in neuroendocrine cells of bronchial mucosa in fetal and infant lungs. Lung tissue from 8 dead newborns with RDS were investigated immunohistochemically with anti-GHR and anti-Try antibodies. The number of GHR+ and Try+ MCs was determined in three locations –bronchi, bronchiole and in alveolar septa. MCs were more numerous around main bronchi with diminishing numbers around bronchiole and in alveolar septa. The number of MCs in the latter was increased in newborns with pneumonia. The number of GHR+ MCs in alveolar septa was lower in newborns with RDS as compared to newborns with RDS combined with pneumonia (2.83 ± 1.13 vs 4.81 ± 2.6, p &lt; 0.001). The amount of Try+ MCs along bronchial wall was significantly more than GHR+ MCs in RDS newborns (6.97 ± 4.53 vs 3.85 ± 4.30, p = 0.001). It could be supposed that pulmonary MCs increased in newborn lungs in inflammatory process. MCs in human lung contained GHR peptide that had immunomodulatory function and participated in hormone regulation of inflammation.

Essentials for aerosol delivery to term and pre-term infants.

Effectively delivering pharmaceutical aerosols to the lungs of preterm and term infants represents a considerable technical challenge. Small infants are obligatory nose breathers, they have small airways, low tidal volumes and rapid respiration rates. It is ethically unacceptable to investigate aerosol deposition in vivo in newborns due to ethical concerns about the radiation exposure involved in imaging studies and drug delivery and blood draws in pharmacokinetics studies. The purpose of the work reported in this article was thus to report the use of modeling to develop an understanding of the regional deposition of aerosols in neonates and to build a theoretical basis for choosing an optimum aerosol size to maximize delivery and minimize variability. Recent data on aerosol deposition in the nasal airways of newborn term and preterm infants was coupled to an established, scalable, lung deposition model to investigate the effects of age, aerosol size and ventilation on regional airway deposition. In the term newborn infant lung deposition ranged from 25% to 35% depending on Geometric Standard Deviations (GSDs). Intrasubject variability was minimized for aerosols with larger GSD. However, mean lung deposition is reduced with increasing GSD. A compromise between maximum lung deposition and increased intersubject variability appears to be in the region of GSDs of 1.75. In the 30-week GA preterm infant lung deposition is slightly higher than in the term infant despite smaller airways and lower tidal volumes. This is likely due to the lower inhaled flow rates that are concomitant with lower lung volumes. Finally, when aerosol delivery is directly to the trachea, as it would be if delivered via an endotracheal tube there is a monotonic increase in lung deposition with increasing aerosol size with peripheral deposition peaking at 2 to 3 µm. However, practical limitations of aerosol transport through endotracheal tubes, limiting delivered aerosol size, likely caps lung deposition at around 30% to 30% of the delivered dose.

Airway basal stem cells generate distinct subpopulations of PNECs.

SUMMARYPulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors.

Maternal Prenatal Hair Cortisol Is Associated with Child Wheeze among Mothers and Infants with Tobacco Smoke Exposure and Who Face High Socioeconomic Adversity

The association of co-occurring prenatal stress and tobacco exposures on childhood wheezing and asthma are not well established. In this study, we compared maternal prenatal hair cortisol concentration (HCC) to the maternal report of infant wheezing (y/n) in the first year of life among mother–infant dyads exposed to tobacco smoke and socioeconomic adversity. Data were obtained from the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function study. Maternal adversity was defined by the level of education, household income, and health insurance provider. Hair was collected at delivery, representing average circulating third-trimester cortisol levels. HCC was log transformed and dichotomized into high/low cortisol groups that were placed into a multivariate model predicting wheeze. Subjects (n = 132) were primarily White with ≤high school education and receiving government-provided health insurance. Forty-five percent of infants wheezed. Average HCC was 3.39 pg/mg hair. Women with HCC > 3.55 pg/mg were more than twice as likely to report having a child who wheezed (odds ratio 2.56, 95% confidence interval 1.22–5.40; p = 0.01), adjusting for insurance provider and maternal asthma. Among this sample of dyads with prenatal smoke exposure, elevated maternal HCC was associated with child wheeze that was not diminished after consideration of covariates.

Malignant pleural effusions

may have already occurred, thus providing a rich environment for growth of P. aeruginosa. Nevertheless, the lack of improvement in lung function measures, despite aggressive treatment and apparent eradiation of P. aeruginosa, is concerning. This finding emphasizes the importance of employing preventative therapy before the development of airway inflammation and infection. Driven by detailed work performed in laboratories such as that described in this issue of the Journal, infant lung function testing has now entered a new stage and can be considered a clinical outcome measure, similar to spirometry in the older child. The raised-volume technique has been standardized (12), published reference values are available (14), procedural risks are acceptable, and studies have clearly demonstrated that this technique is suitable to discriminate lung disease from health (3–5). Results from a recently completed trial performed in infants with CF in the United States are encouraging as they demonstrate the feasibility of studying infant lung function in a multicenter setting when strict quality assurance and training is implemented (15). The tremendous progress in this area of measuring infant physiology will naturally lead to intervention studies using these parameters as outcome measures. Over the next decade, we expect that techniques such as infant and preschool lung function testing will not only improve our understanding of the once ‘‘silent’’ and mysterious young CF lung but will also help us to develop stronger evidence for potential early intervention strategies in this vulnerable age group (16).

Maternal asthma is associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts

RationaleAsthma in pregnancy is associated with respiratory diseases in the offspring.ObjectiveTo investigate if maternal asthma is associated with lung function in early life.MethodsData on lung function measured at 5–6 weeks...

MicroRNA 219-5p inhibits alveolarization by reducing platelet derived growth factor receptor-alpha

BackgroundMicroRNA (miR) are small conserved RNA that regulate gene expression post-transcription. Previous genome-wide analysis studies in preterm infants indicate that pathways of miR 219-5p are important in infants with Bronchopulmonary Dysplasia (BPD).MethodsHere we report a prospective cohort study of extremely preterm neonates wherein infants diagnosed with severe BPD expressed increased airway miR-219-5p and decreased platelet derived growth factor receptor alpha (PDGFR-α), a target of mir-219-5p and a key regulator of alveolarization, compared to post-conception age-matched term infants.ResultsmiR-219-5p was highly expressed in the pulmonary epithelial lining in lungs of infants with BPD by in situ hybridization of human infant lungs. In both in vitro and in vivo (mouse) models of BPD, miR-219-5p was increased on exposure to hyperoxia compared with the normoxia control, with a complementary decrease of PDGFR-α. To further confirm the target relationship between miR‐219 and PDGFR-α, pulmonary epithelial cells (MLE12) and lung primary fibroblasts were treated with a mimic of miR-219-5p and a locked nucleic acid (LNA) based inhibitor of miR-219-5p. In comparison with the control group, the level of miR‐219 increased significantly after miR‐219 mimic treatment, while the level of PDGFR-α declined markedly. LNA exposure increased PDGFR-α. Moreover, in BPD mouse model, over-expression of miR-219-5p inhibited alveolar development, indicated by larger alveolar spaces accompanied by reduced septation.ConclusionsTaken together, our results demonstrate that increased miR-219-5p contributes to the pathogenesis of BPD by targeting and reducing PDGFR-α. The use of specific miRNA antagonists may be a therapeutic strategy for preventing the development of BPD.

A comparison of cannula insufflation device performance for emergency front of neck airway.

Pediatric emergency front of neck airway guidelines recommend oxygenation via cannula cricothyroidotomy or tracheotomy. The primary aim was to measure test lung pressures and volumes generated by cannula insufflation devices recommended for emergency front of neck airway compared with a pressure limit of 50cm H2 O and volume limit of 20ml/kg. The secondary aim was to calculate pressure and volume variability. The primary end point was test lung expansion. Adult, child, and infant airway models, each with three degrees of upper airway obstruction, were oxygenated using six cannula insufflation devices: 3-way stopcock, Rapid-O2 , Manujet, Enk oxygen flow modulator, Ventrain, and self-inflating bags. Test lung pressures and volumes were recorded. Pressures and volumes from all devices were highly variable, despite oxygen flow calibration and strict adherence to oxygen insufflation protocols. With upper airway occlusion, pressures >50cm H2 0 were produced by Rapid-O2 and Enk oxygen flow meter in adult and infant lungs, 3-way stopcock in adult and child lungs, and Manujet in all lung sizes. Ventrain produced acceptable pressures <35cm H2 O in all models. Test lung volumes >20ml/kg were recorded in airway models with fully obstructed proximal airways using Rapid-O2 and Enk oxygen flow meter in infant lungs, and Manujet in all lung sizes. Rapid-O2 produced lung volumes >20ml/kg in the infant model with partially obstructed and open upper airways. Test lung volumes >20ml/kg were produced by the 3-way stopcock in adult, child, and infant models. Insufflation was unsuccessful with the self-inflating bag. Ventrain produced acceptable volumes <7ml/kg in all airway models. Rapid-O2 , Enkoxygen flow meter, Manujet, and 3-way stopcock oxygenation devices produced highly variable and excessive airway pressures and volumes in models with obstructed upper airways. Self-inflating bag insufflation was unsuccessful. Ventrain was the only device that insufflated oxygen with acceptable pressures and volumes in adult, child, and infant airway models with any degree of airway obstruction.

Insufficient development of vessels and alveoli in lungs of infants with trisomy 18-Features of pulmonary histopathological findings from lung biopsy.

The aim of this study was to evaluate the features of pulmonary histopathological changes in cases of trisomy 18 complicated with congenital heart disease and pulmonary arterial hypertension. Twenty-eight patients with trisomy 18 underwent open lung biopsy at the time of primary operation in our hospital between 2008 and 2019. We compared these histopathological findings with those from previously described groups without trisomy 18. Mean age at primary cardiac surgery was 37 days (range, 9-69 days). According to the Heath-Edwards (HE) classification, 1, 8, 12, and 5 patients were graded as 0, 1, 2, and 3, respectively, whereas 2 patients were not classifiable due to medial defects in the small pulmonary arteries (MD). Four (14.3%) and 13 (46.4%) patients presented with MD and hypoplasia of the small pulmonary arteries (HS). Fifteen (53.6%) and 21 (75.0%) patients presented with alveolar hypoplasia (AH) and alveolar wall thickening (AT). MD, HS, and AH in trisomy 18 were present frequently, differing significantly from previous reports. These findings might be associated with congenital inadequate development of vessels and alveoli in the lung, contributing to a high risk of PAH in trisomy 18.

Cord blood group 2 innate lymphoid cells are associated with lung function at 6weeks of age.

ObjectiveOffspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10‐fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy.MethodsCord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t‐distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep.ResultsOf 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty‐four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor‐homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age.”ConclusionFoetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life.

Ultrashort inspiratory times homogenize ventilation distribution in an inhomogeneous two-compartment model of the neonatal lung.

Inhomogeneous lung ventilation and pulmonary air leaks are common adverse effects of mechanical ventilation in preterm infants suffering from respiratory distress syndrome. We hypothesized that shortening of inspiratory times can improve the homogeneity of lung aeration. We assumed that ultrashort inspiratory times lead to a full build-up of pressure in regions with low compliance while maintaining incomplete filling of regions with high compliance. We connected a two-compartment model of the lung with different compliances of the two compartments to a neonatal ventilator. Pressures and flow rates were measured separately for each compartment at inspiratory times ranging from 0.1 to 0.8 s and various combinations of tidal volumes. An inspiratory time of 0.8 s resulted in near total pressure equalization between the airway pressure and the two compartments, as 97% of the maximum applied peak pressure was reached in the low compliance compartment and 95% in the high compliance compartment. The distribution of the tidal volume was proportional to the compartment compliance. Ultrashort inspiratory times lowered the peak pressure and tidal volume in the high compliance compartment but maintained higher pressure and volume in the low compliance compartment. An inspiratory time of 0.2 s resulted in a peak pressure of 80% of peak airway pressure in the low compliance compartment and in 61% of peak airway pressure in the high compliance compartment (p < .001). Ventilation with ultrashort inspiratory times may improve homogeneity of air distribution in inhomogeneous lungs of ventilated preterm or term infants.

Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome.

BackgroundInfants born at extremely low gestational age are at high risk for bronchopulmonary dysplasia and continuing lung disease. There are no early clinical biomarkers for pulmonary outcome and limited therapeutic interventions.ObjectivesWe performed global proteomics of premature infant tracheal aspirate (TA) and plasma to determine the composition and source of lung fluid proteins and to identify potential biomarkers of respiratory outcome.MethodsTA samples were collected from intubated infants in the TOLSURF cohort before and after nitric oxide treatment, and plasma was collected from NO CLD infants. Protein abundance was assayed by HPLC/tandem mass spectrometry and Protein Prospector software. mRNA abundance in mid-gestation fetal lung was assessed by RNA sequencing. Pulmonary morbidity was defined as a need for ventilatory support at term and during the first year.ResultsAbundant TA proteins included albumin, hemoglobin, and actin-related proteins. 96 of 137 detected plasma proteins were present in TA (r = 0.69, p<0.00001). Based on lung RNAseq data, ~88% of detected TA proteins in injured infant lung are derived at least in part from lung epithelium with overrepresentation in categories of cell membrane/secretion and stress/inflammation. Comparing 37 infants at study enrollment (7–14 days) who did or did not develop persistent pulmonary morbidity, candidate biomarkers of both lung (eg., annexin A5) and plasma (eg., vitamin D-binding protein) origin were identified. Notably, levels of free hemoglobin were 2.9-fold (p = 0.03) higher in infants with pulmonary morbidity. In time course studies, hemoglobin decreased markedly in most infants after enrollment coincident with initiation of inhaled nitric oxide treatment.ConclusionsWe conclude that both lung epithelium and plasma contribute to the lung fluid proteome in premature infants with lung injury. Early postnatal elevation of free hemoglobin and heme, which are both pro-oxidants, may contribute to persistent lung disease by depleting nitric oxide and increasing oxidative/nitrative stress.