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.

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.

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.

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.

Pulmonary Gas Exchange Improves over the First Year in Preterm Infants with and without Bronchopulmonary Dysplasia.

BACKGROUND: Right shift of the peripheral oxyhaemoglobin saturation (SpO2) versus inspired oxygen pressure (PIO2) curve is a sensitive marker of pulmonary gas exchange. OBJECTIVES: The aim of this study was to assess the impact of prematurity and bronchopulmonary dysplasia (BPD) on gas exchange and right-to-left shunt in the neonatal period, and its evolution over the first year of life. METHOD: We assessed shift and shunt in extremely preterm (EP) and very preterm (VP) infants at 36 and 44 weeks' postmenstrual age (PMA), and at 1-year corrected postnatal age (cPNA). PIO2 was decreased stepwise to achieve SpO2 between 85 and 98%. Shift and shunt were calculated from paired SpO2/PIO2 measurements using customized software. Results were examined cross-sectionally at each time point, and longitudinally using generalized linear regression. Term infants were assessed at 44 wk PMA as a comparative reference. RESULTS: Longitudinal modelling showed continuous decline in shift in EP and VP infants during the first year of life. There was no difference in shift compared to term infants at 44 wk PMA (p = 0.094). EP infants with BPD had higher shift than infants without BPD at 36 wk PMA (p < 0.001) and 44 wk PMA (p = 0.005) but not at 1-year cPNA. CONCLUSIONS: In the absence of lung disease, prematurity per se did not result in reduced gas exchange at 1-year cPNA. We report ongoing, significant improvements in pulmonary gas exchange in all preterm infants during the first year of life, despite evidence of early deficits in gas exchange in EP infants with BPD.

Maternal Exposure to Indoor Air Pollution and Birth Outcomes.

There is a growing body of research on the association between ambient air pollution and adverse birth outcomes. However, people in high income countries spend most of their time indoors. Pregnant women spend much of that time at home. The aim of this study was to investigate if indoor air pollutants were associated with poor birth outcomes. Pregnant women were recruited prior to 18 weeks gestation. They completed a housing questionnaire and household chemical use survey. Indoor pollutants, formaldehyde (HCHO), nitrogen dioxide (NO2) and volatile organic compounds (VOCs), were monitored in the women's homes at 34 weeks gestation. Gestational age (GA), birth weight (BW) and length (BL) and head circumference (HC) were collected from birth records. The associations between measured pollutants, and pollution surrogates, were analysed using general linear models, controlling for maternal age, parity, maternal health, and season of birth. Only HCHO was associated with any of the birth outcomes. There was a 0.044 decrease in BW z-score (p = 0.033) and 0.05 decrease in HC z-score (p = 0.06) for each unit increase in HCHO. Although HCHO concentrations were very low, this finding is consistent with other studies of formaldehyde and poor birth outcomes.

Sex estimation using anthropometry of feet and footprints in a Western Australian population.

An important component of forensic investigation is the identification of deceased (and increasingly living) individuals, which is often the role of the forensic anthropologist. One of the most valuable steps towards identification is via a biological profile, developed through the application of population specific standards. In disaster victim identification scenarios, fleshed feet are often recovered in footwear; footprints are another potential source of trace evidence found at crime scenes. In medico-legal investigations, feet and footprints can be useful for extrapolating living height, it is thus expedient to determine whether sex can be estimated from the same anthropometric data. The aim of the present study is to develop accurate sex estimation standards for a contemporary Western Australian population from measurements of the feet and footprints. The sample comprises 200 adults (90 males, 110 females). Three bilateral linear measurements were taken from each foot and seven bilateral measurements were acquired from static footprints obtained using a Podograph. A precision test was first conducted to assess data accuracy and reliability. Measurement data are then analysed using a range of parametric statistical tests. Results show that males were significantly (P<0.001) larger than females for all foot and footprint measurements; cross-validated sex classification accuracies ranged from 71% to 91%. Although in many instances the sex bias was large (>±5%), this study provides viable alternatives for estimating sex in Western Australian individuals with accuracy equivalent to established standards developed from foot bones.

Estimation of stature using anthropometry of feet and footprints in a Western Australian population.

The aim of the study is to develop accurate stature estimation models for a contemporary Western Australian population from measurements of the feet and footprints. The sample comprises 200 adults (90 males, 110 females). A stature measurement, three linear measurements from each foot and bilateral footprints were collected from each subject. Seven linear measurements were then extracted from each print. Prior to data collection, a precision test was conducted to determine the repeatability of measurement acquisition. The primary data were then analysed using a range of parametric statistical tests. Results show that all foot and footprint measurements were significantly (P < 0.01-0.001) correlated with stature and estimation models were formulated with a prediction accuracy of ± 4.673 cm to ± 6.926 cm. Left foot length was the most accurate single variable in the simple linear regressions (males: ± 5.065 cm; females: ± 4.777 cm). This study provides viable alternatives for estimating stature in a Western Australian population that are equivalent to established standards developed from foot bones.

Estimation of sex from hand and handprint dimensions in a Western Australian population.

A number of recent studies have demonstrated that sex can be estimated with a high degree of expected accuracy through the analysis of anthropometric measurements of the hand. Presently, however, the majority of previous related research has been focused on a limited range of global populations. The aim of the present study, therefore, is to evaluate the accuracy of using anthropometric hand measurements for the estimation of sex in a contemporary adult Western Australian population; we also assess if sex can be accurately estimated from the measurement of handprints. The study sample comprises a total of 91 male and 110 female individuals; documented mean age for the males is 38 years (range 19-68) and for the female sample it is 36 years (range 18-63). A total of six linear measurements are taken from each hand and its corresponding print. Measurement data is analysed using basic univariate statistics and a series of direct and stepwise discriminant function analyses are performed to assess the sex classification potential of the hand and handprint variables. All six hand and handprint measurements are sexually dimorphic and sex explains 28.4-61.7% of the sample variance. The breadth and length of the hand contribute most significantly to sex discrimination; cross-validated sex classification accuracies range between 82.6 and 96.5% with a sex bias of ≤5%. We conclude that anthropometric measurements of the hand and handprint can be used to classify sex with a high degree of expected accuracy in a Western Australian population.

Estimation of stature from hand and handprint dimensions in a Western Australian population.

As part of the formulation of a biological profile, the estimation of stature is an important element that provides useful data towards narrowing the pool of potentially matching identities. Recent literature has demonstrated that anthropometry of the hand has considerable promise for the accurate estimation of stature; although the technique has only been tested in a relatively limited range of populations. The aim of the present study, therefore, is to assess the reliability and accuracy of using anthropometric hand measurements for the estimation of stature in a contemporary Western Australian population; we also evaluate whether stature can be accurately estimated from the measurement of handprints. The study sample comprises 91 male and 110 female adult individuals. Following the measurement of stature, seven measurements are taken on each hand and its corresponding print. To establish the reliability of acquiring these measurements, a precision study was performed prior to primary data collection. Measurements data are analysed using basic univariate statistics and simple and multiple regression analyses. Our results show that the degree of measurement error and reliability are well within accepted standards. Stature prediction accuracy using hand and handprint measurements ranges from ±4.74 to 6.53cm, which is comparable to established skeletal standards for the hand. This study provides new forensic standards for the estimation of stature in a Western Australian population and also demonstrates that the measurement and analysis of handprints affords a novel source of profiling data that is statistically quantified.