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.

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.

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.

Predicting Lung Health Trajectories for Survivors of Preterm Birth.

Rates of preterm birth (<37 weeks of gestation) are increasing worldwide. Improved perinatal care has markedly increased survival of very (<32 weeks gestation) and extremely (<28 weeks gestation) preterm infants, however, long term respiratory sequalae are common among survivors. Importantly, individual's lung function trajectories are determined early in life and tend to track over the life course. Preterm infants are impacted by antenatal, postnatal and early life perturbations to normal lung growth and development, potentially resulting in significant shifts from the "normal" lung function trajectory. This review summarizes what is currently known about the long-term lung function trajectories in survivors of preterm birth. Further, this review highlights how antenatal, perinatal and early life factors are likely to contribute to individual lung health trajectories across the life course.

I. EXECUTIVE CONTROL IN EARLY CHILDHOOD.

Executive control (EC) is a central construct in developmental science, although measurement limitations have hindered understanding of its nature and development in young children, relation to social risk, and prediction of important outcomes. Disentangling EC from the foundational cognitive abilities it regulates and that are inherently required for successful executive task completion (e.g., language, visual/spatial perception, and motor abilities) is particularly challenging at preschool age, when these foundational abilities are still developing and consequently differ substantially among children. A novel latent bifactor modeling approach delineated respective EC and foundational cognitive abilities components that undergird executive task performance in a socio demographically stratified sample of 388 preschoolers in a longitudinal, cohort-sequential study. The bifactor model revealed a developmental shift, where both EC and foundational cognitive abilities contributed uniquely to executive task performance at ages 4.5 and 5.25 years, but were not separable at ages 3 and 3.75. Contrary to the view that EC is vulnerable to socio-familial risk, the contributions of household financial and learning resources to executive task performance were not specific to EC but were via their relation to foundational cognitive abilities. EC, though, showed a unique, discriminant relation with hyperactive symptoms late in the preschool period, whereas foundational cognitive abilities did not predict specific dimensions of dysregulated behavior. These findings form the basis for a new, integrated approach to the measurement and conceptualization of EC, which includes dual consideration of the contributions of EC and foundational cognitive abilities to executive task performance, particularly in the developmental context of preschool.

Ice sheets. Reverse glacier motion during iceberg calving and the cause of glacial earthquakes.

Nearly half of Greenland's mass loss occurs through iceberg calving, but the physical mechanisms operating during calving are poorly known and in situ observations are sparse. We show that calving at Greenland's Helheim Glacier causes a minutes-long reversal of the glacier's horizontal flow and a downward deflection of its terminus. The reverse motion results from the horizontal force caused by iceberg capsize and acceleration away from the glacier front. The downward motion results from a hydrodynamic pressure drop behind the capsizing berg, which also causes an upward force on the solid Earth. These forces are the source of glacial earthquakes, globally detectable seismic events whose proper interpretation will allow remote sensing of calving processes occurring at increasing numbers of outlet glaciers in Greenland and Antarctica.

Material effects on V-nanoantenna performance.

There is great interest in aluminum based plasmonic devices due to the relatively high plasma frequency of this material as well as its low cost and self-passivating oxide layer. The passivation layer provides aluminum plasmonics with the long-term stability required for practical applications. While several studies have investigated the impact of this oxide layer on the plasmon resonances of aluminum nanostructures on glass substrates, little is known about the effect of high-refractive index substrates on these resonances. Here we present an investigation of aluminum V-shaped antennas resonant in the visible on a silicon substrate. Through comparison between numerical and experimental results, we show that the aluminium passivation layer has little effect on the antenna resonances by comparing numerical simulations both with and without. We show, however, that inclusion of the native oxide layer of the silicon substrate in numerical models is critical for achieving good agreement with experimental data. Furthermore, we computationally explore the influence of the 1.5 eV interband transition of aluminum on plasmon resonances, and find that its effect on the material properties of the resonant structures results in narrower resonances in the blue part of the spectrum than if it was not present.

The first fluorescent sensor for boronic and boric acids with sensitivity at sub-micromolar concentrations--a cautionary tale.

The first reported fluorescent sensor for boronic and boric acids is actually not a sensor for boronic and boric acids but rather is a sensor for protons; the system is also not the first fluorescent sensor since Alizarin has been used as a fluorescent sensor for boric acids since 1936.

Modular fluorescence sensors for saccharides.

Modular and modular polymer supported fluorescence photoinduced electron transfer (PET) sensors 2 and 3 with two boronic acid receptor units, a pyren-1-yl fluorophore, and hexamethylene linker show selective saccharide binding in aqueous methanolic solution at pH 8.21.

A comparative study of bronchodilator effects of carbuterol and ephedrine.

The bronchodilator effect of carbuterol hydrochloride, a new adrenergic agonist, was compared with that of ephedrine sulfate in 12 patients with bronchial asthma. A 2-mg dosage of carbuterol hydrochloride, three times daily, was used in comparison with a 25-mg dosage of ephedrine sulfate, three times daily. The drugs were orally administered for ten-day periods in a double-blind, randomized manner. After carbuterol therapy, the mean increases in forced expiratory volume in one second and midmaximal expiratory flow rate were significantly greater in a four-hour period than those noticed with ephedrine. A decrease in bronchodilator response to both drugs was noticed on the tenth day. No side effects were noticed with carbuterol at the aforementioned dosage. The results of our study indicate that carbuterol is a safer and more effective bronchodilator than ephedrine.