Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age.

Introduction: Many survivors of preterm birth (<37 weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1 year of age. Methods: Nasal airway epithelial brushings were collected, and primary cell cultures established from term (>37 weeks gestation) and very preterm participants (≤32 weeks gestation). Ex vivo RNA was collected from brushings with sufficient cell numbers and in vitro RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome and GO analysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant. Results: Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in ex vivo samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and IRF1 identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-α2 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg/ml/µg protein, p = 0.03]. IFN-γ production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg/ml/µg protein; p = 0.01] as was IFN-ß [7.8 (2.5) vs. 13.6 (19.5) pg/ml/µg protein, p = 0.01]. Conclusion: Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function.

Unravelling the respiratory health path across the lifespan for survivors of preterm birth.

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely-a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease-a first step towards optimising management approaches for prematurity-associated lung disease.

The cost of respiratory hospitalizations in children with cerebral palsy.

AIM: To establish the burden of respiratory illness in cerebral palsy (CP) on the Western Australian health care system by quantifying the costs of respiratory hospitalizations in children with CP, compared with non-respiratory hospitalizations. METHOD: A 2-year (2014-2015) retrospective study using linked hospital data (excluding emergency department visits), in a population of children with CP in Western Australia aged 18 years and under (median age at hospitalization 7 years; interquartile range 5-12 years). RESULTS: In 671 individuals (57% male) there were 726 emergency hospitalizations, and 1631 elective hospitalizations. Although there were more elective hospitalizations, emergency hospitalizations were associated with longer stays in hospital, and more days in an intensive care unit, resulting in a higher total cost of emergency hospitalizations than elective hospitalizations (total costs: emergency AU$7 748 718 vs elective AU$6 738 187). 'Respiratory' was the leading cause of emergency hospitalizations, contributing to 36% of all emergency admission costs. For a group of high-cost inpatient users (top 5% of individuals with the highest total inpatient costs) the most common reason for hospitalization was 'respiratory'. Where non-respiratory admissions were complicated by an additional respiratory diagnosis, length of stay was greater. INTERPRETATION: Respiratory hospitalizations in CP are a significant driver of health care costs. In the paediatric group, they are a burden for a subgroup of children with CP. WHAT THIS PAPER ADDS: Respiratory illness is the most costly area for unplanned, emergency hospitalizations for children and young people with cerebral palsy. The top 5% of individuals with the highest total inpatient costs account for a disproportionate amount of health care costs.

Preterm birth and exercise capacity: what do we currently know?

Objectives: The long-term cardiopulmonary outcomes following preterm birth during the surfactant era remain unclear. Respiratory symptoms, particularly exertional symptoms, are common in preterm children. Therefore, cardiopulmonary exercise testing may provide insights into the pathophysiology driving exertional respiratory symptoms in those born preterm. This review aims to outline the current knowledge of cardiopulmonary exercise testing in the assessment of children born preterm in the surfactant era. Design: This study is a narrative literature review. Methods: Published manuscripts concerning the assessment of pulmonary outcomes using cardiopulmonary exercise testing in preterm children (aged <18 years) were reviewed. Search terms related to preterm birth, bronchopulmonary dysplasia, and exercise were entered into electronic databases, including Medline, PubMed, and Google Scholar. Reference lists from included studies were scanned for additional manuscripts. Results: Preterm children have disrupted lung development with significant structural and functional lung disease and increased respiratory symptoms. The association between these (resting) assessments of respiratory health and exercise capacity is unclear; however, expiratory flow limitation and an altered ventilatory response (rapid, shallow breathing) are seen during exercise. Due to the heterogeneity of participants, treatments, and exercise protocols, the effect of the aforementioned limitations on exercise capacity in children born preterm is conflicting and poorly understood. Conclusion: Risk factors for reduced exercise capacity in those born preterm remain poorly understood; however, utilizing cardiopulmonary exercise testing to its full potential, the pathophysiology of exercise limitation in survivors of preterm birth will enhance our understanding of the role exercise may play. The role of exercise interventions in mitigating the risk of chronic disease and premature death following preterm birth has yet to be fully realized and should be a focus of future robust randomized controlled trials.

Elevated leukotriene B4 and 8-isoprostane in exhaled breath condensate from preterm-born infants.

BACKGROUND: Inflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (< 32 weeks gestation) at 12-16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity. METHODS: EBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data. RESULTS: Leukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term (mean difference [95% CI]; 1.52 [0.45, 2.59], p = 0.02; 0.77 [0.52, 1.02], p < 0.001, respectively). Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life. CONCLUSIONS: Infants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health. TRIAL REGISTRATION: N/A.

Oscillometry and spirometry are not interchangeable when assessing the bronchodilator response in children and young adults born preterm.

INTRODUCTION: The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes. METHODS: Participants aged 6-23 born ≤32 (N = 288; 132 with bronchopulmonary dysplasia) and ≥37 weeks' gestation (N = 76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400 µg salbutamol was classified according to published criteria. RESULTS: A BDR was identified in 30.9% (n = 85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k = 0.26; 95% confidence interval [CI] 0.18-0.40, p < .001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs. 11%, p = .010) and baseline resistance (Rrs5 z-score mean difference (MD) = 0.86, 95% CI 0.07-1.65, p = .025), but similar baseline spirometry to the group without a BDR (forced expiratory volume in 1 s [FEV1 ] z-score MD = -0.01, 95% CI -0.66 to 0.68, p > .999). Oscillometry was more feasible than spirometry (95% success rate vs. 85% (FEV1 ), 69% (forced vital capacity) success rate, p < .001), however being born preterm did not affect test feasibility. CONCLUSION: In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to those measured by spirometry, and thus these tests should not be used interchangeably.

Health service utilisation for acute respiratory infections in infants graduating from the neonatal intensive care unit: a population-based cohort study.

BACKGROUND: Despite advances in neonatal intensive care, babies admitted to Neonatal Intensive Care Units (NICU) suffer from adverse outcomes. We aim to describe the longer-term respiratory infectious morbidity of infants discharged from NICU using state-wide population-based linked data in Western Australia. STUDY DESIGN: We used probabilistically linked population-based administrative data to analyse respiratory infection morbidity in a cohort of 23,784 infants admitted to the sole tertiary NICU, born 2002-2013 with follow up to 2015. We analysed incidence rates of secondary care episodes (emergency department presentations and hospitalisations) by acute respiratory infection (ARI) diagnosis, age, gestational age and presence of chronic lung disease (CLD). Poisson regression was used to investigate the differences in rates of ARI hospital admission between gestational age groups and those with CLD, after adjusting for age at hospital admission. RESULTS: From 177,367 child-years at risk (i.e., time that a child could experience an ARI outcome), the overall ARI hospitalisation rate for infants and children aged 0-8 years was 71.4/1000 (95% confidence interval, CI: 70.1, 72.6), with the highest rates in infants aged 0-5 months (242.9/1000). For ARI presentations to emergency departments, equivalent rates were 114/1000 (95% CI: 112.4, 115.5) and 337.6/1000, respectively. Bronchiolitis was the most common diagnosis among both types of secondary care, followed by upper respiratory tract infections. Extremely preterm infants (< 28 weeks gestation at birth) were 6.5 (95% CI: 6.0, 7.0) times more likely and those with CLD were 5.0 (95% CI: 4.7, 5.4) times more likely to be subsequently admitted for ARI than those in NICU who were not preterm or had CLD after adjusting for age at hospital admission. CONCLUSIONS: There is an ongoing burden of ARI in children who graduate from the NICU, especially those born extremely preterm, that persists into early childhood. Early life interventions to prevent respiratory infections in these children and understanding the lifelong impact of early ARI on later lung health are urgent priorities.

Inhaled corticosteroids to improve lung function in children (aged 6-12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population. METHODS: PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 µg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246. FINDINGS: Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV1 Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition). INTERPRETATION: As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease. FUNDING: Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.

Increasing airway obstruction through life following bronchopulmonary dysplasia: a meta-analysis.

Background: Few studies exist investigating lung function trajectories of those born preterm; however growing evidence suggests some individuals experience increasing airway obstruction throughout life. Here we use the studies identified in a recent systematic review to provide the first meta-analysis investigating the impact of preterm birth on airway obstruction measured by the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. Methods: Cohorts were included for analysis if they reported FEV1/FVC in survivors of preterm birth (<37 weeks' gestation) and control populations born at term. Meta-analysis was performed using a random effect model, expressed as standardised mean difference (SMD). Meta-regression was conducted using age and birth year as moderators. Results: 55 cohorts were eligible, 35 of which defined groups with bronchopulmonary dysplasia (BPD). Compared to control populations born at term, lower values of FEV1/FVC were seen in all individuals born preterm (SMD -0.56), with greater differences seen in those with BPD (SMD -0.87) than those without BPD (SMD -0.45). Meta-regression identified age as a significant predictor of FEV1/FVC in those with BPD with the FEV1/FVC ratio moving -0.04 sds away from the term control population for every year of increased age. Conclusions: Survivors of preterm birth have significantly increased airway obstruction compared to those born at term with larger differences in those with BPD. Increased age is associated with a decline in FEV1/FVC values suggesting increased airway obstruction over the life course.

Risk factors for poorer respiratory outcomes in adolescents and young adults born preterm.

RATIONALE: The respiratory outcomes for adult survivors of preterm birth in the postsurfactant era are wide-ranging with prognostic factors, especially those encountered after the neonatal period, poorly understood. OBJECTIVES: To obtain comprehensive 'peak' lung health data from survivors of very preterm birth and identify neonatal and life-course risk factors for poorer respiratory outcomes in adulthood. METHODS: 127 participants born ≤32 weeks gestation (64%, n=81 with bronchopulmonary dysplasia (BPD), initially recruited according to a 2 with-BPD:1 without-BPD strategy), and 41 term-born controls completed a lung health assessment at 16-23 years, including lung function, imaging and symptom review. Risk factors assessed against poor lung health included neonatal treatments, respiratory hospitalisation in childhood, atopy and tobacco smoke exposure. MEASUREMENTS AND MAIN RESULTS: Young adults born prematurely had greater airflow obstruction, gas trapping and ventilation inhomogeneity, in addition to abnormalities in gas transfer and respiratory mechanics, compared with term. Beyond lung function, we observed greater structural abnormalities, respiratory symptoms and inhaled medication use. A previous respiratory admission was associated with airway obstruction; mean forced expiratory volume in 1 s/forced vital capacity z-score was -0.561 lower after neonatal confounders were accounted for (95% CI -0.998 to -0.125; p=0.012). Similarly, respiratory symptom burden was increased in the preterm group with a respiratory admission, as was peribronchial thickening (6% vs 23%, p=0.010) and bronchodilator responsiveness (17% vs 35%, p=0.025). Atopy, maternal asthma and tobacco smoke exposure did not influence lung function or structure at 16-23 years in our preterm cohort. CONCLUSIONS: Even after accounting for the neonatal course, a respiratory admission during childhood remained significantly associated with reduced peak lung function in the preterm-born cohort, with the largest difference seen in those with BPD. A respiratory admission during childhood should, therefore, be considered a risk factor for long-term respiratory morbidity in those born preterm, especially for individuals with BPD.

Normal values of respiratory oscillometry in South African children and adolescents.

Introduction: Noninvasive measurement of respiratory impedance by oscillometry can be used in young children aged from 3 years and those unable to perform forced respiratory manoeuvres. It can discriminate between healthy children and those with respiratory disease. However, its clinical application is limited by the lack of reference data for African paediatric populations. The aim of the present study was to develop reference equations for oscillometry outcomes in South African children and adolescents. Methods: Healthy subjects, enrolled in the Drakenstein Child Health Study, HIV-uninfected adolescents in the Cape Town Adolescent Antiretroviral Cohort and healthy children attending surgical outpatient clinics at Red Cross War Memorial Children's Hospital were measured with conventional spectral (6-32 Hz) and intra-breath (10 Hz) oscillometry. Stepwise linear regression was used to assess the relationship between respiratory variables and anthropometric predictors (height, sex, ancestry) to generate reference equations. Results: A total of 692 subjects, 48.4% female, median age of 5.2 years (range: 3-17 years) were included. The median (interquartile range (IQR)) for weight for age z-score and height for age z-score was -0.42 (-1.11-0.35) and -0.65 (-1.43-0.35), respectively. Stepwise regression demonstrated that all the variables were significantly dependent on height only. Comparison to previous reference data indicated slightly higher resistance and lower compliance values in the smallest children. Conclusion: We established the first respiratory oscillometry reference equations for African children and adolescents, which will facilitate use in early identification and management of respiratory disease. Our results suggest differences in oscillometry measures by ancestry but also highlight the lack of standardisation in methodology.

Ventilatory response and stability of oxygen saturation during a hypoxic challenge in very preterm infants.

BACKGROUND: Preterm infants have immature control of breathing and impaired pulmonary gas exchange. We hypothesized that infants with bronchopulmonary dysplasia (BPD) have a blunted ventilatory response and peripheral oxygen saturation (SpO2 ) instability during a hypoxic challenge. METHODS: We evaluated the response to hypoxia in 57 very preterm infants (38 no BPD, 10 mild BPD, 9 moderate-to-severe BPD) at 36 weeks' postmenstrual age. The fraction of inspired oxygen (FI O2 ) was reduced stepwise at 5-min intervals to achieve peripheral SpO2 between 86% and 95%. The lowest permissible FI O2 and SpO2 were 0.14% and 86%. We recorded SpO2 , FI O2 , and the respiratory signal (respiratory inductive plethysmography). We calculated respiratory rate (RR), tidal volume (VT ), minute ventilation (VE ), and respiratory drive (ratio between VT and inspiratory time, VT /TI ). SpO2 variability was expressed as the interquartile range (IQR). RESULTS: FI O2 was reduced from a median (Q1, Q3) of 0.21 (0.21, 0.21) to 0.17 (0.17, 0.18). We observed a marked individual variability in the ventilatory response to the hypoxic challenge, regardless of BPD severity. At the lowest permissible FI O2 , 37 (65%) infants reduced their VE , and 20 (35%) increased minute ventilation; 20 infants (35%) developed periodic breathing associated with increased SpO2 IQR and lower SpO2 minima, and 16 (28%) exhibited an oscillatory pattern in VE and SpO2 without end-expiratory pauses, regardless of BPD severity. CONCLUSION: In very preterm infants, a mild hypoxic challenge reduced ventilation, increased SpO2 variability and periodic breathing regardless of BPD severity.

The ventilatory response to hypoxia is blunted in some preterm infants during the second year of life.

Background: Preterm birth and subsequent neonatal ventilatory treatment disrupts development of the hypoxic ventilatory response (HVR). An attenuated HVR has been identified in preterm neonates, however it is unknown whether the attenuation persists into the second year of life. We investigated the HVR at 12-15 months corrected postnatal age and assessed predictors of a blunted HVR in those born very preterm (<32 weeks gestation). Methods: HVR was measured in infants born very preterm. Hypoxia was induced with a three-step reduction in their fraction of inspired oxygen (FIO2) from 0.21 to 0.14. Respiratory frequency (f), tidal volume (V T), minute ventilation (V E), inspiratory time (t I), expiratory time (t E), V T/t I, tI/t TOT, V T/t TOT, area under the low-volume loop and peak tidal expiratory flow (PTEF) were measured at the first and third minute of each FIO2. The change in respiratory variables over time was assessed using a repeated measures ANOVA with Greenhouse-Geisser correction. A blunted HVR was defined as a <10% rise in V E, from normoxia. The relationship between neonatal factors and the magnitude of HVR was assessed using Spearman correlation. Results: Thirty nine infants born very preterm demonstrated a mean (SD) HVR of 11.4 (10.1)% (increase in V E) in response to decreasing FIO2 from 0.21 to 0.14. However, 17 infants (44%) failed to increase V E by ≥10% (range -14% to 9%) and were considered to have a blunted response to hypoxia. Males had a smaller HVR than females [ΔV E (-9.1%; -15.4, -2.8; p = 0.007)]. Conclusion: Infants surviving very preterm birth have an attenuated ventilatory response to hypoxia that persists into the second year of life, especially in males.

Living with lung disease: experimental models to assess the long-term effects of prematurity.

Laboratory models provide an important tool in helping to understand the cellular and molecular drivers of respiratory disease. Many animal models exist that model the neonatal outcomes of preterm birth. Discoveries at the laboratory bench from examination of both human tissue and tissues from animal models have informed the life-saving technologies and clinical care used today. Yet animal laboratory models of preterm birth have rarely been utilized beyond the neonatal period, despite growing reports of respiratory symptoms and subnormal lung function throughout childhood. Elucidation of the driving factors and physiological explanations underpinning poor outcomes in survivors of preterm birth are crucial to optimize clinical care and identify therapeutic targets. Can existing neonatal models be utilized to study respiratory outcomes beyond infancy? This review answers the question by highlighting the clinical evidence underpinning an active respiratory disease process after preterm birth and exploring the benefits and drawbacks of existing models to conduct research into the long-term respiratory outcomes of preterm birth.

Geographical Differences and Temporal Improvements in Forced Expiratory Volume in 1 Second of Preterm-Born Children: A Systematic Review and Meta-analysis.

Importance: Although preterm birth is associated with later deficits in lung function, there is a paucity of information on geographical differences and whether improvements occur over time, especially after surfactant was introduced. Objective: To determine deficits in percentage predicted forced expiratory volume in 1 second (%FEV1) in preterm-born study participants, including those with bronchopulmonary dysplasia (BPD) in infancy, when compared with term-born control groups. Data Sources: Eight databases searched up to December 2021. Study Selection: Studies reporting spirometry for preterm-born participants with or without a term-born control group were identified. Data Extraction and Synthesis: Data were extracted and quality assessed by 1 reviewer and checked by another. Data were pooled using random-effects models and analyzed using Review Manager and the R metafor package. Main Outcomes and Measures: Deficits in %FEV1 between preterm-born and term groups. Associations between deficits in %FEV1 and year of birth, age, introduction of surfactant therapy, and geographical region of birth and residence were also assessed. Results: From 16 856 titles, 685 full articles were screened: 86 with and without term-born control groups were included. Fifty studies with term controls were combined with the 36 studies from our previous systematic review, including 7094 preterm-born and 17 700 term-born participants. Of these studies, 45 included preterm-born children without BPD, 29 reported on BPD28 (supplemental oxygen dependency at 28 days), 26 reported on BPD36 (supplemental oxygen dependency at 36 weeks' postmenstrual age), and 86 included preterm-born participants. Compared with the term-born group, the group of all preterm-born participants (all preterm) had deficits of %FEV1 of -9.2%; those without BPD had deficits of -5.8%, and those with BPD had deficits of approximately -16% regardless of whether they had BPD28 or BPD36. As year of birth increased, there was a statistically significant narrowing of the difference in mean %FEV1 between the preterm- and term-born groups for the all preterm group and the 3 BPD groups but not for the preterm-born group without BPD. For the all BPD group, when compared with Scandinavia, North America and western Europe had deficits of -5.5% (95% CI, -10.7 to -0.3; P = .04) and -4.1% (95% CI, -8.8 to 0.5; P = .08), respectively. Conclusions and Relevance: Values for the measure %FEV1 were reduced in preterm-born survivors. There were improvements in %FEV1 over recent years, but geographical region had an association with later %FEV1 for the BPD groups.

Clinical significance and applications of oscillometry.

Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.

Confidence in airway management proficiency: a mixed methods study of intensive care specialists in Australia and New Zealand.

Objective: To explore self-confidence, and the respective facilitators and barriers, among intensive care specialists in Australia and New Zealand in relation to airway management. Design: A mixed methods study. Setting: 11 intensive care units across Australia and New Zealand. Participants: 48 intensive care specialists. Intervention: A structured online interview and the presentation of three discrete airway management clinical scenarios - routine endotracheal intubation, awake fibreoptic intubation (AFOI), and emergency front of neck access (FONA). Main outcome measures: Graded Likert scale responses regarding confidence in airway management were analysed, and perceptions of facilitators and barriers to confidence in each select scenario were obtained as free text. A deductive thematic analysis was done iteratively on free text entry and allowed for the development of a coding framework. NVivo software used the coding framework to run coding queries and cross-tabulations for comparison of relationships between themes and participant demographic characteristics. Results: Participants reported differing levels of confidence. Clinical experience, an anaesthetic qualification and training (including simulation) were the major facilitators to influencing confidence. Participants were more confident performing routine intubation than AFOI or FONA. Equipment, checklists or protocols, and availability of video-laryngoscopy were also identified as facilitators to confidence by most participants. Work relationships, teams and other staff availability were identified as further facilitators to confidence; lack of these factors were less commonly identified as barriers. Conclusions: Confidence in airway management among intensive care specialists in Australia and New Zealand varies, both between specialists and depending on clinical context. Multiple facilitators to improving this exist, including additional mandatory training.

Nasal airway epithelial repair after very preterm birth.

Nasal epithelial cells from very preterm infants have a functional defect in their ability to repair beyond the first year of life, and failed repair may be associated with antenatal steroid exposure https://bit.ly/39OFJs7.